CSPM EDP Sciences logo
Access to submission and peer review system
Search
Menu
All issues Volume 6 (2025) Vis Cancer Med, 6 (2025) 6 Full HTML
Open Access
Issue
Vis Cancer Med
Volume 6, 2025
Article Number 6
Number of page(s) 7
DOI https://doi.org/10.1051/vcm/2025007
Published online 20 April 2025

© The Authors, published by EDP Sciences, 2025

Licence Creative CommonsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction

The recent awarding of the Nobel Prize in physiology or medicine to Victor R. Ambros and Gary B. Ruvkun, pioneers in the discovery of microRNAs (miRNAs), highlights the pivotal role of miRNAs within the gene regulatory network. Since the first discovery of miRNA in 1993 [1, 2], scientists have undertaken comprehensive investigations into miRNAs. The specific mechanisms and physiological roles of miRNAs have been substantially clarified. Notably, their profound influence on tumorigenesis and cancer progression has attracted significant scholarly attention. This article elaborates on the current status of the clinical application of microRNA in cancer screening, diagnosis, treatment and prognostic prediction, also discusses its possible future development directions.

MicroRNA biology: A pivotal regulatory system in cancer formation and development

The oncogenic and tumor-suppressive roles, along with the underlying mechanisms of miRNAs in diverse cancers, have been extensively investigated [3]. Frequently, miRNAs post-transcriptionally regulate the target mRNA expression through complementary base pairing. However, miRNAs can also exert regulatory functions through several unconventional mechanisms, such as coding for peptides [4], activating Toll-like receptors [5], and even directly modulating transcription [6]. One of the earliest discovered miRNAs, let-7, is associated with the poorly differentiated phenotype of cancer cells and serves as a biomarker for advanced stages of cancer [7]. Furthermore, the downregulation of let7 has been shown to augment cellular transformation and tumorigenesis, thereby underscoring its role as a tumor suppressor [8, 9]. In contrast, miR-21 is a prototypical oncogenic miRNA that facilitates cancer invasion and metastasis by directly targeting the phosphatase and tensin homolog (PTEN) pathway [10]. Our recent findings demonstrate that miR-25-3p in pancreatic ductal epithelial cells suppresses PHLPP2, thereby activating the oncogenic AKT-p70S6K signaling pathway and promoting the malignant phenotype of pancreatic cancer cells. This underscores the significance of RNA modification in the oncogenic effects mediated by miRNAs [11]. The regulatory roles of miRNAs in cancer are too numerous and complex to be fully discussed in this context. Plainly, miRNAs have a crucial impact on the entire process of cancer occurrence, development, and even treatment.

Clinical application potentials

Although some miRNAs exhibit dual roles in cancer and there is complexity in physiological effects due to their potential interaction with multiple mRNAs, specific miRNA expression patterns have been identified in almost all cancer types in the past two decades. For instance, our research team identified the microRNA MIR548K encoded in the amplified 11q13.3 - 13.4 region in esophageal squamous cell carcinoma cells as a novel oncogene 10 years ago [12]. Various studies, ranging from bioinformatics analyses to clinical research, have also revealed a strong correlation between cancer-specific miRNA expression and clinical outcomes such as prognosis and drug resistance [13, 14]. Moreover, the unique stability of miRNA in tissues, especially in blood, also gives better clinical diagnostic performance [15, 16].

An extensive body of preclinical research indicates that miRNA-based therapeutics can markedly impede cancer progression. In various cancer cell lines, the selective targeting or delivery of specific miRNAs has been shown to mitigate their malignant phenotypes [17, 18]. Furthermore, miRNA-based therapeutic strategies have demonstrated promising outcomes in patient-derived tumor organoids as well as in multiple preclinical models [19–21]. Recently, the siRNA-derived drug inclisiran has successfully completed phase II clinical trials and safety evaluations, demonstrating remarkable efficacy [22–24]. These results highlight the therapeutic potential of small RNA-based interventions and reinforce our confidence in the clinical applicability of miRNAs, which are also small RNAs.

In the clinic, the use of miRNAs to assist in cancer diagnosis and treatment has undeniable value, and the optimization of miRNA utilization strategies represents a crucial focal point in our current research agenda.

Screening and diagnosis

Particular miRNAs expression profiles act as pivotal biomarkers in oncology, facilitating the precise detection of early-stage malignancies and contributing to the evaluation of therapeutic resistance and prognostic outcomes. Recent advancements in detection materials have enhanced the accuracy and sensitivity of miRNA-based diagnostics [25]. Furthermore, the advancement of multifunctional platforms that integrate miRNA separation and detection, exemplified by microfluidic digital microfluidic workstations [26], has significantly contributed to the automation, miniaturization, and ease of use in miRNA detection.

Localization marker

As early as 2007, Bloomston et al. identified miRNA expression profiles capable of distinguishing pancreatic cancer from normal pancreatic tissue or chronic pancreatitis. They also found that the high expression of miR-196a-2 could predict poor survival outcomes [27]. Subsequently, a cohort study found that patients with low expression of miR-26 in liver cancer had shorter overall survival but a better response to interferon therapy [28]. An increasing number of studies have revealed the significant potential of using miRNA profiles from biopsy tissue samples for clinical cancer diagnosis and therapeutic guidance. Based on these foundations, a series of clinical diagnostic trials have been initiated. For instance, miR-155 has been employed in the diagnosis of bladder cancer (ClinicalTrials.gov identifier: NCT03591367). Additionally, miRNA expression profiling is utilized for predicting the progression of breast cancer (ClinicalTrials.gov identifier: NCT04516330). The miRNAs used for diagnosis and prognosis prediction in primary tumors of various organs [11, 27, 29–54] are shown in Figure 1.

thumbnail Figure 1

Local miRNAs of primary tumors of visceral organ for diagnostic and prognostic. Image created by Figdraw.

Peripheral marker

The detection of peripheral samples such as blood, body fluids, and even feces for cancer diagnosis can significantly enhance the convenience and efficiency of cancer diagnosis. In 2008, a case-control study was conducted that identified 38 markedly dysregulated miRNAs in the blood samples of pancreatic cancer patients. Subsequently, two diagnostic panels consisting of multiple miRNAs were constructed. These diagnostic panels demonstrated excellent diagnostic efficacy for pancreatic cancer. Notably, when combined with CA19-9, an even higher area under the curve (AUC) could be attained [55]. Similarly, compared with active ulcerative colitis, miR-375 was significantly upregulated in the blood of patients with colitis-associated cancer, indicating its potential as a blood marker for identifying colitis-associated cancer [56]. Additionally, a clinical trial to identify specific miRNAs in fecal samples for the diagnosis of colorectal cancer is underway (ClinicalTrials.gov identifier: NCT05346757), providing a new insight for non-invasive cancer examination.

Building on previous fundamental research, translational studies on the clinical application of miRNAs have shown promising trends and contributed to the advancement of precision oncology. However, there remains a vast space for further exploration of miRNA basic research, particularly in terms of the impact of epigenetic factors such as m 6 A [11] on miRNA, which require more in-depth investigation.

Anti-cancer treatment

MiRNA-based cancer therapies encompass two primary strategies: the use of specific miRNA inhibitors to target oncogenic miRNAs (oncomiRs) and miRNA mimics to enhance tumor-suppressive miRNAs (ts-miRs). The first human miRNA clinical trial was conducted in 2013. Although some patients experienced common adverse events and the trial was prematurely terminated due to a severe immune reaction [57], it nonetheless provided proof of concept for miRNA-based targeted cancer therapy. The clinical trial database supported by the National Institutes of Health (clinicaltrials.gov) shows that the total number of clinical studies on miRNA-based cancer treatment has reached 200, which adequately illustrates the broad prospects of microRNA in clinical oncology.

Targeting OncomiR

Antisense oligonucleotides (ASOs or antimiRs), miRNA sponges, and the CRISPR/CAS9 system can all be employed to inhibit the function of intracellular miRNAs. Due to the fact that naked miRNA strands do not meet the ideal requirements in terms of specificity, stability, and membrane penetration ability, they are often chemically modified to enhance stability and target affinity. For example, cholesterol-conjugated antimiRs and locked nucleic acid antimiRs (LNA), which contain a methylene bridge connecting the 2′-O atom and 4′-C atom, both displayed higher thermal stability and unprecedented hybridization affinity to their targets [58, 59]. Nevertheless, several limitations persist, including suboptimal targeting efficacy, sequence-independent toxicity associated with certain chemical modifications, and challenges in delivering these agents to organs beyond the liver [60]. miRNA sponges can inhibit miRNA function by competitively binding to miRNA, but their effects are unstable and the precise control of dosage remains challenging. In recent years, the CRISPR/Cas9 system has made substantial progress in clinical applications, particularly within the realm of cancer treatment. The modification of CAR-T cells via CRISPR technology has significantly augmented its cytotoxic activity against tumor cells [61, 62]. Nevertheless, concerns persist regarding off-target effects when using the CRISPR/Cas9 system to manipulate miRNA expression in tumor cells in vivo. Therefore, there is a pressing need for the development of more efficient delivery vectors to achieve greater cell-specificity.

Ts-miR supplementation

The supplementation of tumor-suppressive miRNAs using miRNA mimics is only active when delivered to the cytoplasm, thus necessitating the support of an efficient delivery system. Current delivery systems can be categorized into natural-source carriers and artificial carriers. Natural-source carriers include cell-derived exosomes, AGO proteins [63–65], bacteria and virus-derived carriers [66–68], as well as natural polymer molecular carriers. Among these, carriers derived from bacteria and viruses require more cautious application due to their strong immunogenicity and potential toxicity. In contrast, exosomes and AGO proteins exhibit low immunogenicity, low toxicity, high stability, and can maintain the activity of miRNAs or their mimics. However, they possess limited targeting ability and a short duration of activity. Currently, exosomes can be modified with specific ligands of target cell membrane proteins to improve their targeting ability [69]. They can also deliver both miRNAs and chemotherapy drugs simultaneously, significantly broadening their clinical applicability. Nevertheless, they still face the challenge of low nucleic acid loading efficiency. Genetically engineered fusion RNA binding protein to promote RNA concentration and loading or combination with other delivery systems may be a potential solution. Chitosan nanocarriers are a type of natural polymer carrier with relatively good biodegradability, biocompatibility, and potential for increased functional modification, but have limited water solubility, a slow dissociation rate in cells, and low transfection efficiency. Artificial carriers are diverse, include plasmonic nanoparticles, liposomes, cell-penetrating peptides, etc. Based on the unique optical properties at the nanoscale, plasmonic nanoparticles have been utilized in cancer photothermal therapy. After loading miRNA, the miRNA fixed on the photo-responsive gold nanoshell surface can be released by continuous wave (CW) or nanosecond-pulsed NIR light, thus achieving precise gene regulation [70]. Liposomes can encapsulate RNA in the lipid bilayer or its aqueous core and can also be combined with other nanodelivery technologies, such as encapsulating cell-penetrating peptide-RNA complexes and magnetic nanoparticles [71]. But the first miRNA human trial used a liposome delivery system, and subsequent more clinical trials have shown that liposomes may be the main source of its immunotoxicity [57]. Although various miRNA carrier systems emerge in an endless stream, each offering distinct improvements and advantages, they also present several limitations. Perhaps the integration of multiple delivery systems through the invention of new materials or technologies is the key to meeting the requirements.

Clinical practice

Preclinical studies have demonstrated the high efficacy of miRNA-based cancer treatment. Although recent clinical trials have yielded restricted results (Table 1), its significant potential in clinical treatment persists: MRX34 demonstrated a manageable toxicity profile in most patients and some clinical activity [57]; TargomiRs, loaded with miR-16 mimics, target cancer cells with high epidermal growth factor receptor (EGFR) expression, thereby supplementing the deficiency of miR-16 in these cells. Notably, among the participants, one patient achieved a partial response. This trial demonstrates latent hope for further investigations of TargomiRs in combination with chemotherapy or immune checkpoint inhibitors [72]. The antisense oligonucleotide cobomarsen (MRG-106) that targets and inhibits miR-155 was tested for five cycles of treatment in one patient, stabilizing the tumor growth without obvious side effects, demonstrating its acceptable safety profile [73]. Encouragingly, a large number of clinical studies on miRNA-based cancer treatment are still underway. Let us look forward to their results and guide the application of miRNA in cancer.

Table 1

Clinical trials on miRNA-based cancer treatment.

Future perspective

Since the discovery of miRNAs, research on cancer-related miRNAs has surged, yielding a wealth of foundational theories and motivating scientists to prioritize translational research [74]. Cancer precision phenotypes and biomarkers play a fundamental role in ensuring the efficiency and specificity of delivery systems. As miRNA delivery systems evolve, research into cancer precision phenotypes and biomarkers with high specificity and sensitivity becomes increasingly critical. Notably, there is a concern regarding the potency of the anticancer effect when targeting a single miRNA. Although preclinical studies have yielded satisfactory outcomes, the current results of human trials are not truly captivating. Certainly, the application of miRNA in human cancer therapy is still in its early stages and requires continued patience and further investigation.

The miRNA alterations in malignancy are often complicated and multifaceted with miRNA-specific profiles existing in each cancer subtype. To achieve more accurate diagnosis and prognostic prediction, comprehensive analyses involving multiple miRNA networks are essential. miRNA may drive the heterogeneity of cancer cells within a tumor. Regulating the global miRNA profile to eliminate this heterogeneity and render the tumor uniformly sensitive to other treatments represents a possible direction. Additionally, given the important impact of miRNA on chemotherapy sensitivity, the combined application of multiple miRNAs and chemotherapy drugs, encapsulated in a delivery system to ensure simultaneous delivery to the lesion site, is believed to enhance therapeutic efficacy by targeting multiple pathways [75].

Cancer treatment can be a long-term procedure, therefore the sustainable application of miRNA-based therapy is crucial for controlling cancer progression and preventing cancer recurrence. The development of more stable and efficient modified forms of miRNA, along with the creation of miRNA storage and sustained release systems, like subcutaneous or local implantation for long-term drug delivery effects, all need to be emphasized. This will require collaboration across multiple disciplines, including clinical oncology, pharmacokinetics, nanotechnology, materials science, and chemistry. The full cooperation of scientists across various fields is believed to pave the way for cancer treatment and bring new and hopeful vitality to patients.

MicroRNAs represent a vast repository and an essential element of hierarchical regulation of gene expression. It exerts an indispensable function in pathophysiology, particularly in the dysregulation of gene expression associated with cancer. The utilization of miRNA in clinical settings is a long-term subject with boundless potential. Current clinical trials involving miRNAs are just the beginning of a promising field. Let us anticipate the moment when miRNA shines resplendently in cancer treatment.

Funding

This research did not receive any specific funding.

Conflicts of interest

The authors declare that they have no conflicts of interest in relation to this article.

Data availability statement

Data sharing is not applicable to this article.

Author contribution statement

Canbin Ye is responsible for conceptualization and manuscript writing, Jian Zheng is responsible for manuscript editing and proofreading.

Ethics approval

Ethical approval was not required.

References

  1. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993; 75(5):843–854. [CrossRef] [PubMed] [Google Scholar]
  2. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75(5):855–862. [CrossRef] [PubMed] [Google Scholar]
  3. Lee YS, Dutta A. MicroRNAs in cancer. Annual Review of Pathology. (2009);4:199–227. [CrossRef] [PubMed] [Google Scholar]
  4. Lauressergues D, Couzigou JM, Clemente HS, Martinez Y, Dunand C, Bécard G, et al. Primary transcripts of microRNAs encode regulatory peptides. Nature. 2015;520(7545):90–93. [CrossRef] [PubMed] [Google Scholar]
  5. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(31):E2110–E2116. [PubMed] [Google Scholar]
  6. Matsui M, Chu Y, Zhang H, Gagnon KT, Shaikh S, Kuchimanchi S, et al. Promoter RNA links transcriptional regulation of inflammatory pathway genes. Nucleic Acids Research. 2013;41(22):10086–10109. [CrossRef] [PubMed] [Google Scholar]
  7. Shell S, Park SM, Radjabi AR, Schickel R, Kistner EO, Jewell DA, et al. Let-7 expression defines two differentiation stages of cancer. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(27):11400–11405. [CrossRef] [PubMed] [Google Scholar]
  8. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Natature Genetics. 2007;39(5):673–677. [CrossRef] [PubMed] [Google Scholar]
  9. Liu Y, Li K, Zhang J, Jin L, Xu H, Duan Y. Let-7 reduces the proliferation and migration of oral cancer cells via PI3K/AKT signaling pathway. Journal of Biochemical and Molecular Toxicology. 2024;38(9):e23834. [CrossRef] [PubMed] [Google Scholar]
  10. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007;133(2):647–658. [CrossRef] [PubMed] [Google Scholar]
  11. Zhang J, Bai R, Li M, Ye H, Wu C, Wang C, et al. Excessive miR-25-3p maturation via N(6)-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression. Nature Communications. 2019;10(1):1858. [CrossRef] [PubMed] [Google Scholar]
  12. Song Y, Li L, Ou Y, Gao Z, Li E, Li X, et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature. 2014;509(7498):91–95. [CrossRef] [PubMed] [Google Scholar]
  13. Madurantakam Royam M, Kumarasamy C, Baxi S, Gupta A, Ramesh N, Kodiveri Muthukaliannan G, et al. Current evidence on miRNAs as potential theranostic markers for detecting chemoresistance in colorectal cancer: a systematic review and meta-analysis of preclinical and clinical studies. Molecular Diagnosis and Therapy. 2019;23(1):65–82. [CrossRef] [PubMed] [Google Scholar]
  14. Zhang C, Sun C, Zhao Y, Wang Q, Guo J, Ye B, et al. Overview of MicroRNAs as diagnostic and prognostic biomarkers for high-incidence cancers in 2021. International Journal of Molecular Sciences. 2022;23(19):11389. [CrossRef] [PubMed] [Google Scholar]
  15. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(30):10513–10518. [CrossRef] [PubMed] [Google Scholar]
  16. Wu P, Zhang C, Tang X, Li D, Zhang G, Zi X, et al. Pan-cancer characterization of cell-free immune-related miRNA identified as a robust biomarker for cancer diagnosis. Molecular Cancer 2024;23(1):31. [CrossRef] [PubMed] [Google Scholar]
  17. Bergamini C, Leoni I, Rizzardi N, Melli M, Galvani G, Coada CA, et al. MiR-494 induces metabolic changes through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma. Journal of Experimental and Clinical Cancer Research. 2023;42(1):145. [CrossRef] [Google Scholar]
  18. Yuan M, Mahmud I, Katsushima K, Joshi K, Saulnier O, Pokhrel R, et al. miRNA-211 maintains metabolic homeostasis in medulloblastoma through its target gene long-chain acyl-CoA synthetase 4. Acta Neuropathologica Communications. 2023;11(1):203. [CrossRef] [PubMed] [Google Scholar]
  19. Oshima G, Poli EC, Bolt MJ, Chlenski A, Forde M, Jutzy JMS, et al. DNA methylation controls metastasis-suppressive 14q32-encoded miRNAs. Cancer Research. 2019;79(3):650–662. [CrossRef] [PubMed] [Google Scholar]
  20. Hu HF, Xu WW, Zhang WX, Yan X, Li YJ, Li B, et al. Identification of miR-515–3p and its targets, vimentin and MMP3, as a key regulatory mechanism in esophageal cancer metastasis: functional and clinical significance. Signal Transduction and Targeted Therapy. 2020;5(1):271. [CrossRef] [PubMed] [Google Scholar]
  21. Gilles ME, Hao L, Huang L, Rupaimoole R, Lopez-Casas PP, Pulver E, et al. Personalized RNA medicine for pancreatic cancer. Clinical Cancer Research. 2018;24(7):1734–1747. [CrossRef] [PubMed] [Google Scholar]
  22. Ray KK, Stoekenbroek RM, Kallend D, Nishikido T, Leiter LA, Landmesser U, et al. Effect of 1 or 2 doses of inclisiran on low-density lipoprotein cholesterol levels: one-year follow-up of the ORION-1 randomized clinical trial. JAMA Cardiology. 2019;4(11):1067–1075. [CrossRef] [PubMed] [Google Scholar]
  23. Ray KK, Stoekenbroek RM, Kallend D, Leiter LA, Landmesser U, Wright RS, et al. Effect of an siRNA therapeutic targeting PCSK9 on atherogenic lipoproteins: prespecified secondary end points in ORION 1. Circulation. 2018;138(13):1304–1316. [CrossRef] [PubMed] [Google Scholar]
  24. Ray KK, Troquay RPT, Visseren FLJ, Leiter LA, Scott Wright R, Vikarunnessa S, et al. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes and Endocrinology. 2023;11(2):109–119. [CrossRef] [Google Scholar]
  25. Miti A, Thamm S, Müller P, Csáki A, Fritzsche W, Zuccheri G. A miRNA biosensor based on localized surface plasmon resonance enhanced by surface-bound hybridization chain reaction. Biosensors and Bioelectronics. 2020;167:112465. [CrossRef] [Google Scholar]
  26. Tong Z, Xu X, Shen C, Yang D, Li Y, Li Q, et al. All-in-one multiple extracellular vesicle miRNA detection on a miniaturized digital microfluidic workstation. Biosensors and Bioelectronics. 2024;270:116976. [Google Scholar]
  27. Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007;297(17):1901–1908. [CrossRef] [PubMed] [Google Scholar]
  28. Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, et al. MicroRNA expression, survival, and response to interferon in liver cancer. New England Journal of Medicine. 2009;361(15):1437–1447. [CrossRef] [PubMed] [Google Scholar]
  29. Shen X, Lin Z, Jiang X, Zhu X, Zeng S, Cai S, et al. Dumbbell probe initiated multi-rolling circle amplification assisted CRISPR/Cas12a for highly sensitive detection of clinical microRNA. Biosensors and Bioelectronics. 2024;264:116676. [CrossRef] [Google Scholar]
  30. Migdalska-Sęk M, Modrzewska B, Kordiak J, Pastuszak-Lewandoska D, Kiszałkiewicz JM, Bielec F, et al. Diagnostic value of PPARδ and miRNA-17 expression levels in patients with non-small cell lung cancer. Scientific Reports. 2021;11(1):24136. [CrossRef] [PubMed] [Google Scholar]
  31. Nie R, Niu W, Tang T, Zhang J, Zhang X. Integrating microRNA expression, miRNA-mRNA regulation network and signal pathway: a novel strategy for lung cancer biomarker discovery. PeerJ. 2021;9:e12369. [CrossRef] [PubMed] [Google Scholar]
  32. Yang J, Hao R, Zhang Y, Deng H, Teng W, Wang Z. Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer. Cancer Cell International. 2021;21(1):611. [CrossRef] [PubMed] [Google Scholar]
  33. Qin S, Xu J, Yi Y, Jiang S, Jin P, Xia X, et al. Transcription factors and methylation drive prognostic miRNA dysregulation in hepatocellular carcinoma. Frontiers in Oncology. 2021;11:691115. [CrossRef] [PubMed] [Google Scholar]
  34. Huang XC, Pang FX, Ou SS, Wei XJ, Xu YJ, Lai YH. Risk score based on two microRNAs as a prognostic marker of hepatocellular carcinoma and the corresponding competitive endogenous RNA network. International Journal of General Medicine. 2021;14:3377–3385. [CrossRef] [Google Scholar]
  35. Yu Z, Rong Z, Sheng J, Luo Z, Zhang J, Li T, et al. Aberrant non-coding RNA expressed in gastric cancer and its diagnostic value. Frontiers in Oncology. 2021;11:606764. [CrossRef] [PubMed] [Google Scholar]
  36. Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299(4):425–436. [PubMed] [Google Scholar]
  37. Liu Z, Lu T, Wang Y, Jiao D, Li Z, Wang L, et al. Establishment and experimental validation of an immune miRNA signature for assessing prognosis and immune landscape of patients with colorectal cancer. Journal of Cellular and Molecular Medicine. 2021;25(14):6874–6886. [CrossRef] [PubMed] [Google Scholar]
  38. Lan SH, Lin SC, Wang WC, Yang YC, Lee JC, Lin PW, et al. Autophagy upregulates miR-449a expression to suppress progression of colorectal cancer. Frontiers in Oncology. 2021;11:738144. [CrossRef] [PubMed] [Google Scholar]
  39. Lal M, Ansari AH, Agrawal A, Mukhopadhyay A. Diagnostic and prognostic potential of MiR-379/656 MicroRNA cluster in molecular subtypes of breast cancer. Journal of Clinical Medicine. 2021;10(18):4071. [CrossRef] [PubMed] [Google Scholar]
  40. Xing AY, Wang B, Li YH, Chen X, Wang YW, Liu HT, et al. Identification of miRNA signature in breast cancer to predict neoadjuvant chemotherapy response. Pathology Oncology Research. 2021;27:1609753. [CrossRef] [PubMed] [Google Scholar]
  41. Rönnau CGH, Fussek S, Smit FP, Aalders TW, van Hooij O, Pinto PMC, et al. Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer. World Journal of Urology. 2021;39(10):3789–3797. [CrossRef] [PubMed] [Google Scholar]
  42. Stoen MJ, Andersen S, Rakaee M, Pedersen MI, Ingebriktsen LM, Bremnes RM, et al. High expression of miR-17–5p in tumor epithelium is a predictor for poor prognosis for prostate cancer patients. Scientific Reports. 2021;11(1):13864. [CrossRef] [PubMed] [Google Scholar]
  43. Liu J, Quan Z, Gao Y, Wu X, Zheng Y. MicroRNA-199b-3p suppresses malignant proliferation by targeting Phospholipase Cε and correlated with poor prognosis in prostate cancer. Biochemical and Biophysical Research Communications. 2021;576:73–79. [CrossRef] [PubMed] [Google Scholar]
  44. Permuth-Wey J, Thompson RC, Burton Nabors L, Olson JJ, Browning JE, Madden MH, et al. A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma. Journal of Neuro-Oncology. 2011;105(3):639–646. [CrossRef] [PubMed] [Google Scholar]
  45. Matos B, Bostjancic E, Matjasic A, Popovic M, Glavac D. Dynamic expression of 11 miRNAs in 83 consecutive primary and corresponding recurrent glioblastoma: correlation to treatment, time to recurrence, overall survival and MGMT methylation status. Radiology and Oncology. 2018;52(4);422–432. [CrossRef] [PubMed] [Google Scholar]
  46. Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8. Oncogene. 2011;30(7):806–821. [CrossRef] [PubMed] [Google Scholar]
  47. Li Y, Huang Y, Qi Z, Sun T, Zhou Y. MiR-338–5p promotes glioma cell invasion by regulating TSHZ3 and MMP2. Cellular and Molecular Neurobiology. 2018;38(3):669–677. [CrossRef] [PubMed] [Google Scholar]
  48. Ye Z, Zhang Z, Wu L, Liu C, Chen Q, Liu J, et al. Upregulation of miR-183 expression and its clinical significance in human brain glioma. Neurological Sciences. 2016;37(8):1341–1347. [CrossRef] [PubMed] [Google Scholar]
  49. Al-Temaimi R, Abdulkarim B, Al-Ali A, John B, Mallik MK, Kapila K. Analysis of candidate miRNAs’ expression in pancreatic cancer. Cancer Medicine. 2024;13(21):e70400. [CrossRef] [PubMed] [Google Scholar]
  50. Frampton AE, Giovannetti E, Jamieson NB, Krell J, Gall TM, Stebbing J, et al. A microRNA meta-signature for pancreatic ductal adenocarcinoma. Expert Review of Molecular Diagnostics. 2014;14(3):267–271. [CrossRef] [PubMed] [Google Scholar]
  51. Szafranska AE, Davison TS, John J, Cannon T, Sipos B, Maghnouj A, et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene. 2007;26(30):4442–4452. [CrossRef] [PubMed] [Google Scholar]
  52. Zhang W, Hong R, Li L, Wang Y, Du P, Ou Y, et al. The chromosome 11q13.3 amplification associated lymph node metastasis is driven by miR-548k through modulating tumor microenvironment. Molecular Cancer. 2018;17(1):125. [CrossRef] [PubMed] [Google Scholar]
  53. Lin Z, Chen Y, Lin Y, Lin H, Li H, Su X, et al. Potential miRNA biomarkers for the diagnosis and prognosis of esophageal cancer detected by a novel absolute quantitative RT-qPCR method. Scientific Reports. 2020;10(1):20065. [CrossRef] [PubMed] [Google Scholar]
  54. Xue J, Jia E, Ren N, Xin H. Identification of prognostic miRNA biomarkers for esophageal cancer based on the cancer genome atlas and gene expression omnibus. Medicine. 2021;100(7);e24832. [CrossRef] [PubMed] [Google Scholar]
  55. Schultz NA, Dehlendorff C, Jensen BV, Bjerregaard JK, Nielsen KR, Bojesen SE, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014;311(4):392–404. [CrossRef] [PubMed] [Google Scholar]
  56. Patel M, Verma A, Aslam I, Pringle H, Singh B. Novel plasma microRNA biomarkers for the identification of colitis-associated carcinoma. Lancet (London, England). 2015;385(Suppl 1):S78. [CrossRef] [PubMed] [Google Scholar]
  57. Hong DS, Kang YK, Borad M, Sachdev J, Ejadi S, Lim HY, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. British Journal of Cancer. 2020;122(11):1630–1637. [CrossRef] [PubMed] [Google Scholar]
  58. Wengel J, Vester B, Lundberg LB, Douthwaite S, Sørensen MD, Babu BR, et al. LNA and alpha-L-LNA: towards therapeutic applications. Nucleosides, Nucleotides and Nucleic Acids. 2003;22(58):601–604. [CrossRef] [PubMed] [Google Scholar]
  59. Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with “antagomirs”. Nature. 2005;438(7068):685–689. [CrossRef] [PubMed] [Google Scholar]
  60. Khvorova A, Watts JK. The chemical evolution of oligonucleotide therapies of clinical utility. Nature Biotechnology. 2017;35(3):238–248. [CrossRef] [PubMed] [Google Scholar]
  61. Li LL, Xia YP, Li Q, Wang P, Sun PP, Wang XG, et al. Case report: CD7-targeted autologous CAR-T therapy for the treatment of T-cell acute lymphoblastic leukemia undergoing allogeneic peripheral blood stem cell transplantation in the long-term follow-up. Frontiers in Immunology. 2024;15:1469251. [CrossRef] [PubMed] [Google Scholar]
  62. Stadtmauer EA, Fraietta JA, Davis MM, Cohen AD, Weber KL, Lancaster E, et al. CRISPR-engineered T cells in patients with refractory cancer. Science (New York, NY). 2020;367(6481):eaba7365. [CrossRef] [PubMed] [Google Scholar]
  63. Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(12):5003–5008. [CrossRef] [PubMed] [Google Scholar]
  64. Ferreira R, Santos T, Amar A, Gong A, Chen TC, Tahara SM, et al. Argonaute-2 promotes miR-18a entry in human brain endothelial cells. Journal of the American Heart Association. 2014;3(3):e000968. [CrossRef] [PubMed] [Google Scholar]
  65. Fareh M, Almairac F, Turchi L, Burel-Vandenbos F, Paquis P, Fontaine D, et al. Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth. Cell Death and Disease. 2017;8(3):e2713. [CrossRef] [Google Scholar]
  66. Ashley CE, Carnes EC, Phillips GK, Durfee PN, Buley MD, Lino CA, et al. Cell-specific delivery of diverse cargos by bacteriophage MS2 virus-like particles. ACS Nano. 2011; 5(7):5729–5745. [CrossRef] [PubMed] [Google Scholar]
  67. Ahmed O, Krühn A, Lage H. Delivery of siRNAs to cancer cells via bacteria. Methods in Molecular Biology (Clifton, NJ). 2015;1218:117–129. [CrossRef] [PubMed] [Google Scholar]
  68. Chen SK, Hawley ZCE, Zavodszky MI, Hana S, Ferretti D, Grubor B, et al. Efficacy and safety of a SOD1-targeting artificial miRNA delivered by AAV9 in mice are impacted by miRNA scaffold selection Molecular Therapy Nucleic Acids. 2023;34:102057. [CrossRef] [PubMed] [Google Scholar]
  69. Zhang Y, Liu Q, Zhang X, Huang H, Tang S, Chai Y, et al. Recent advances in exosome-mediated nucleic acid delivery for cancer therapy. Journal of Nanobiotechnology. 2022;20(1):279. [CrossRef] [PubMed] [Google Scholar]
  70. Dang MN, Gomez Casas C, Day ES. Photoresponsive miR-34a/nanoshell conjugates enable light-triggered gene regulation to impair the function of triple-negative breast cancer cells. Nano Letters. 2021;21(1):68–76. [CrossRef] [PubMed] [Google Scholar]
  71. Yang Y, Xie X, Xu X, Xia X, Wang H, Li L, et al. Thermal and magnetic dual-responsive liposomes with a cell-penetrating peptide-siRNA conjugate for enhanced and targeted cancer therapy. Colloids and Surfaces B, Biointerfaces. 2016;146:607–615. [CrossRef] [Google Scholar]
  72. van Zandwijk N, Pavlakis N, Kao SC, Linton A, Boyer MJ, Clarke S, et al. Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study. Lancet Oncology. 2017;18(10):1386–1396. [CrossRef] [Google Scholar]
  73. Anastasiadou E, Seto AG, Beatty X, Hermreck M, Gilles ME, Stroopinsky D, et al. Cobomarsen, an oligonucleotide inhibitor of miR-155, slows DLBCL tumor cell growth in vitro and in vivo. Clinical Cancer Research. 2021;27(4):1139–1149. [CrossRef] [PubMed] [Google Scholar]
  74. Waldman SA, Terzic A. Translating MicroRNA discovery into clinical biomarkers in cancer. JAMA. 2007; 297(17);1923–1925. [CrossRef] [PubMed] [Google Scholar]
  75. Li S, Saw PE, Lin C, Nie Y, Tao W, Farokhzad OC, et al. Redox-responsive polyprodrug nanoparticles for targeted siRNA delivery and synergistic liver cancer therapy. Biomaterials. 2020;234:119760. [CrossRef] [PubMed] [Google Scholar]

Cite this article as: Ye C & Zheng J. Cancer therapeutics hope: microRNA clinical practice and perspectives. Visualized Cancer Medicine. 2025, 6, 6. https://doi.org/10.1051/vcm/2025007.

All Tables

Table 1

Clinical trials on miRNA-based cancer treatment.

In the text

All Figures

thumbnail Figure 1

Local miRNAs of primary tumors of visceral organ for diagnostic and prognostic. Image created by Figdraw.
In the text

Current usage metrics show cumulative count of Article Views (full-text article views including HTML views, PDF and ePub downloads, according to the available data) and Abstracts Views on Vision4Press platform.

Data correspond to usage on the plateform after 2015. The current usage metrics is available 48-96 hours after online publication and is updated daily on week days.

Initial download of the metrics may take a while.