Open research questions in MicroRNA in disease regulation

What the literature leaves open

• Limited permeability in certain tissues. Need for additional optimization for different tissue types.

  Protocol for high-sensitivity detection of microRNAs in adult Drosophila tissues using hybridization chain reaction · 2026 · DOI

• The prognosis for CML patients remains unfavorable despite significant progress in understanding the molecular mechanisms underlying CML development. There is a need for a deeper understanding of the molecular pathways involved in CML pathogenesis. The study aims to address the gap in understanding the regulatory mechanisms of miR-33a-5p in CML.

  Candidate Regulatory Relationship and Expression Correlation Between miR-33a-5p and ANK3 in Chronic Myeloid Leukemia · 2026 · DOI

• The study highlights the need for further research into the association of microRNAs with obesity and T2DM subgroups. The study identifies a discrepancy between the reported prevalence of NAFLD in men and women, which may be due to differences in study populations or diagnostic selection.

  Expression profiles of selected circulating microRNAs (miR-192-5p and miR-155-3p) in NAFLD and their association with obesity and type 2 diabetes mellitus · 2026 · DOI

• There is a lack of biomarkers for early laryngeal cancer screening. Prior studies have not investigated the potential of miR-31-3p and miR-196a-5p as biomarkers for LSCC.

  Integration of Circulating miR-31-3p and miR-196a-5p as Liquid Biopsy Markers in HPV-Negative Primary Laryngeal Squamous Cell Carcinoma · 2025 · DOI

• The research highlights the need for reliable, minimally invasive biomarkers for earlier detection and improved therapeutic monitoring. The study notes the challenge of individual-level variability in miRNA expression, which can be obscured by pooling patient samples.

  A Pilot Study on the Analysis of Circulating miRNA Upregulation in Laryngeal Cancer · 2025 · DOI

• The lack of understanding of microRNA signatures that contribute to the disparities in ovarian cancer mortality rates among women of African ancestry compared to those of European or Asian descent. The need for identification of prognostic markers of overall survival in serous ovarian cancer. The importance of investigating race-associated molecular differences in serous ovarian cancer.

  MicroRNA Signatures in Serous Ovarian Cancer: A Comparison of Prognostic Marker Targets in African Americans and Caucasians · 2025 · DOI

• The field of miRNA-based therapeutics is still in its early stages, with only a few miRNA therapeutics entering clinical trials. None of the miRNA therapeutics have entered phase III or been approved by the FDA, and several have been terminated due to toxicity. There is a need to address the existing challenges, such as toxicity issues, for the broad clinical application of miRNA-based therapeutics.

  Trials and Tribulations of MicroRNA Therapeutics · 2024 · DOI

• The current understanding of miR-223-3p's role in cancer development and drug resistance is limited. Further research is needed to understand the miRNA's context-dependent function. The paper identifies a gap in the current literature regarding the use of miR-223-3p as a diagnostic and prognostic biomarker.

  MiR-223-3p in Cancer Development and Cancer Drug Resistance: Same Coin, Different Faces · 2024 · DOI

• The therapeutic management of gastric neoplasms represents a challenge due to limited curability possibilities. Early detection of gastric cancer is crucial for increasing survival rates. The disease becomes symptomatic only in advanced stages, making early diagnosis challenging.

  In Pursuit of Novel Markers: Unraveling the Potential of miR-106, CEA and CA 19-9 in Gastric Adenocarcinoma Diagnosis and Staging · 2024 · DOI

• The current screening methods are insufficient for early detection. There is a lack of understanding of the role of microRNAs in CRC pathogenesis. The review identifies the need for integrating miRNA diagnostics into current screening methods.

  Advances in microRNAs as Emerging Biomarkers for Colorectal Cancer Early Detection and Diagnosis · 2024 · DOI

• Depression is a debilitating mental illness recognized as one of the leading causes of disability worldwide, and its exact pathogenesis remains poorly understood.

  The Important Role of miR-96 in Depression: New Research Progress and Future Prospects · 2026 · DOI

• Cardiac stress induces MYH6-to-MYH7 remodeling and activates redox-defense programs, but the regulatory mechanisms that distinguish adaptive from maladaptive stress responses remain incompletely defined.

  MiR-208b-3p is an upstream regulator of redox-associated cardiomyocyte survival · 2026 · DOI

• The insulin/insulin-like signaling (IIS) pathway is central to insect growth and metamorphosis, yet its post-transcriptional regulation in stored-product insects remains poorly understood.

  Lse-novel_mir23 Directly Targets LsPI3K21B and Contributes to Pupal–Adult Metamorphosis in the Cigarette Beetle Lasioderma serricorne · 2026 · DOI

• Limited expression of FOLR1 in prostate cancer cells. Potential immunotoxicity associated with miR-34a over-dosing.

  Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises · 2024 · DOI

• The study aims to investigate the expression of miR-146a-5p and miR-146a-3p in patients with inflammatory lung diseases.

  Dual Role of microRNA-146a in Experimental Inflammation in Human Pulmonary Epithelial and Immune Cells and Expression in Inflammatory Lung Diseases · 2024 · DOI

• Further investigation of the candidate regulatory relationship between miR-33a-5p and ANK3, - Development of targeted therapies for CML, - Investigation of the molecular pathways involved in CML…

  Candidate Regulatory Relationship and Expression Correlation Between miR-33a-5p and ANK3 in Chronic Myeloid Leukemia · 2026 · DOI

• The utility of miR-7 as a diagnostic biomarker for PD remains under scrutiny due to inconsistent findings across studies, - influenced by variables such as tissue sources and sample sizes, - Current treatment strategies are mostly limited to symptomatic relief of motor…

  Unravelling the novel insights between miR-7 and Parkinson’s disease (PD) · 2026 · DOI

• Further biological validation is needed to verify the role of miR-7 in PD, - Research on the effect of miR-7 on insulin release in β-cells is required, - Studies on the potential of miR-7 as a therapeutic target for PD…

  Unravelling the novel insights between miR-7 and Parkinson’s disease (PD) · 2026 · DOI

• The study had a limited sample size, - The study population may not be representative of the general population, - There may be bias in diagnostic…

  Expression profiles of selected circulating microRNAs (miR-192-5p and miR-155-3p) in NAFLD and their association with obesity and type 2 diabetes mellitus · 2026 · DOI

• Investigating other miRNAs targeting LsPI3K21B, - Elucidating the molecular mechanisms underlying Lse-novel_mir23-LsPI3K21B interaction, - Exploring RNA-based management strategies for L.

  Lse-novel_mir23 Directly Targets LsPI3K21B and Contributes to Pupal–Adult Metamorphosis in the Cigarette Beetle Lasioderma serricorne · 2026 · DOI

• Further research is essential for the development of miRNAs as effective cancer therapeutics, - Research is needed to address the challenges associated with precisely delivering miRNAs to specific cell types, tissues, and organs, - Studies should investigate the potential of small-molecule drugs in the regulation of miRNA…

  Trials and Tribulations of MicroRNA Therapeutics · 2024 · DOI

• The fact that cardiomyocytes are terminally differentiated and cannot significantly regenerate after injury - The lack of distinct boundaries between different categories of ischemic heart disease - The need to harness unfavorable physical environments to promote exosome…

  Stem Cell Therapy against Ischemic Heart Disease · 2024 · DOI

• Investigating the actions of exosomes - Exploring the therapeutic effects of ischemic-preconditioned exosomes and hypoxia-elicited MSC-derived exosomes - Boosting the therapeutic efficacy of MSC-derived exosomes through noncoding RNA…

  Stem Cell Therapy against Ischemic Heart Disease · 2024 · DOI

• Further research is needed to identify new biomarkers that can optimize personalized treatment, - Research is ongoing to identify new biomarkers for breast cancers, - The potential application of miR-223 as a diagnostic and prognostic biomarker in the clinic needs to be further…

  MiR-223-3p in Cancer Development and Cancer Drug Resistance: Same Coin, Different Faces · 2024 · DOI

• Further exploration of the molecular mechanisms driving cancer invasion and metastasis is needed - Larger studies are required to confirm the findings of this study - Investigation of other potential biomarkers for gastric adenocarcinoma…

  In Pursuit of Novel Markers: Unraveling the Potential of miR-106, CEA and CA 19-9 in Gastric Adenocarcinoma Diagnosis and Staging · 2024 · DOI

Most-cited papers in MicroRNA in disease regulation

• The functions of animal microRNAs · Nature · 2004 · 9,024 citations
• MicroRNA expression profiles classify human cancers · Nature · 2005 · 7,882 citations
• Identification of Novel Genes Coding for Small Expressed RNAs · Science · 2001 · 3,900 citations
• Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs · Nature · 2005 · 3,897 citations
• The nuclear RNase III Drosha initiates microRNA processing · Nature · 2003 · 3,823 citations
• Mammalian microRNAs predominantly act to decrease target mRNA levels · Nature · 2010 · 3,360 citations
• Silencing of microRNAs in vivo with ‘antagomirs’ · Nature · 2005 · 3,353 citations
• The impact of microRNAs on protein output · Nature · 2008 · 3,049 citations
• A microRNA polycistron as a potential human oncogene · Nature · 2005 · 2,921 citations
• Widespread changes in protein synthesis induced by microRNAs · Nature · 2008 · 2,891 citations

Most recent work

• Exercise Immunology Meets MiRNAs · PubMed · 2026
• Is there a role for microRNAs in exercise immunology? - A synopsis of current literature and future developments · PubMed · 2026
• Regulation of immediate early gene expression by exercise: Short cuts for the adaptation of immune function · PubMed · 2026
• MicroRNAs in Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, and Treatment Monitoring · Cells · 2026
• Aerobic exercise stabilizes atherosclerotic plaques by suppressing miR-15a-5p-mediated repression of Semaphorin-3A in vascular smooth muscle cells · Life Sciences · 2026
• Harnessing microRNAs in lung cancer: The future of diagnosis and precision therapy · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · 2026
• Artificial intelligence-based miRNA analysis for precision oncology: diagnostic and prognostic insights · Frontiers in Molecular Biosciences · 2026
• A Personalized Point-of-Care Platform for Discovery and Validation of miRNA Targets Using AI and Edge Computing Supporting Personalized Cancer Therapy · IEEE Journal of Biomedical and Health Informatics · 2026
• Research progress of miRNA in post-stroke cognitive impairment · Brain Research Bulletin · 2026
• Several novel classes of small regulatory RNAs show widespread changes in schizophrenia and bipolar disorder and extensive linkages to critical brain processes · Translational Psychiatry · 2026

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