Aberrant miRNA Expression Research Articles

First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth.

Spontaneous Preterm Delivery (sPTD) is one of the leading causes of perinatal mortality and morbidity worldwide. The present case−control study aims to detect miRNAs differentially expressed in the first trimester maternal plasma with the view to identify predictive biomarkers for sPTD, between 320/7 and 366/7 weeks, that will allow for timely interventions for this serious pregnancy complication. Small RNA sequencing (small RNA-seq) of five samples from women with a subsequent sPTD and their matched controls revealed significant down-regulation of miR-23b-5p and miR-125a-3p in sPTD cases compared to controls, whereas miR-4732-5p was significantly overexpressed. Results were confirmed by qRT-PCR in an independent cohort of 29 sPTD cases and 29 controls. Statistical analysis demonstrated that miR-125a is a promising early predictor for sPTL (AUC: 0.895; 95% CI: 0.814-0.972; p < 0.001), independent of the confounding factors tested, providing a useful basis for the development of a novel non-invasive predictive test to assist clinicians in estimating patient-specific risk.

The Potential of MicroRNAs as Clinical Biomarkers to Aid Ovarian Cancer Diagnosis and Treatment.

Ovarian cancer is a commonly diagnosed malignancy in women. When diagnosed at an early stage, survival outcomes are favourable for the vast majority, with up to 90% of ovarian cancer patients being free of disease at 5 years follow-up. Unfortunately, ovarian cancer is typically diagnosed at an advanced stage due to the majority of patients remaining asymptomatic until the cancer has metastasised, resulting in poor outcomes for the majority. While the molecular era has facilitated the subclassification of the disease into distinct clinical subtypes, ovarian cancer remains managed and treated as a single disease entity. MicroRNAs (miRNAs) are small (19-25 nucleotides), endogenous molecules which are integral to regulating gene expression. Aberrant miRNA expression profiles have been described in several cancers, and have been implicated to be useful biomarkers which may aid cancer diagnostics and treatment. Several preliminary studies have identified candidate tumour suppressor and oncogenic miRNAs which may be involved in the development and progression of ovarian cancer, highlighting their candidacy as oncological biomarkers; understanding the mechanisms by which these miRNAs regulate the key processes involved in oncogenesis can improve our overall understanding of cancer development and identify novel biomarkers and therapeutic targets. This review highlights the potential role of miRNAs which may be utilised to aid diagnosis, estimate prognosis and enhance therapeutic strategies in the management of primary ovarian cancer.

Nomogram for predicted probability of cervical cancer and its precursor lesions using miRNA in cervical mucus, HPV genotype and age

Cervical cancer is the fourth most common cancer in women worldwide. Although cytology or HPV testing is available for screening, these techniques have their drawbacks and optimal screening methods are still being developed. Here, we sought to determine whether aberrant expression of miRNAs in cervical mucus could be an ancillary test for cervical neoplasms. The presence of miRNAs in 583 and 126 patients (validation and external cohorts) was determined by real-time RT-PCR. Performance of a combination with five miRNAs (miR-126-3p, -451a -144-3p, -20b-5p and -155-5p) was estimated by ROC curve analysis. Predicted probability (PP) was estimated by nomograms comprising -ΔCt values of the miRNAs, HPV genotype and age. A combination of five miRNAs showed a maximum AUC of 0.956 (95% CI: 0.933–0.980) for discriminating cancer. Low PP scores were associated with good prognosis over the 2-year observation period (p < 0.05). Accuracy for identifying cancer and cervical intraepithelial neoplasia (CIN) 3 + by nomogram was 0.983 and 0.966, respectively. PP was constant with different storage conditions of materials. We conclude that nomograms using miRNAs in mucus, HPV genotype and age could be useful as ancillary screening tests for cervical neoplasia.

Effects of writers, erasers and readers within miRNA-related m6A modification in cancers.

As one of the most abundant post-transcriptional mRNA modifications, N6-methyladenosine (m6A) has attracted extensive attention from scientists. Emerging evidence indicates that m6A modification plays a significant role in cancer-related signalling pathways. Existing research demonstrates that m6A modifications were also identified in miRNAs and contribute to cancer-related signalling pathways. A literature retrieval has been performed to collect m6A-miRNA-related original articles published in recent years. Later, a systematic analysis has been conducted to abstract and classify the relationships between m6A modification and miRNAs, and their contributions to tumorigenesis and cancer development. Accumulating literature provides important insights into multiple relationships between m6A modifications and miRNAs. Mechanically, m6A writer and eraser alter pri-miRNAs m6A levels, and m6A readers could dually modulate pri-miRNAs processing and pri-miRNAs degradation. It is also been demonstrated that miRNAs impair m6A regulators' translation to influence m6A medication function in return. Aberrant expressions of m6A regulators and miRNAs could dysregulate proliferative, apoptosis, cell adhesion-related, and malignant transformation signalling pathways, and contribute to tumour occurrence and development. This review summarizes the interrelationship between m6A modification and miRNAs; highlights the combined effects of each type of m6A regulator and miRNAs in cancers. These findings enhance our understanding of m6A-miRNAs' multiple interactions and significant modulatory role in tumorigenesis and progression.

Micro-RNAs in Human Placenta: Tiny Molecules, Immense Power.

Micro-RNAs (miRNAs) are short non-coding single-stranded RNAs that modulate the expression of various target genes after transcription. The expression and distribution of kinds of miRNAs have been characterized in human placenta during different gestational stages. The identified miRNAs are recognized as key mediators in the regulation of placental development and in the maintenance of human pregnancy. Aberrant expression of miRNAs is associated with compromised pregnancies in humans, and dysregulation of those miRNAs contributes to the occurrence and development of related diseases during pregnancy, such as pre-eclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), recurrent miscarriage, preterm birth (PTB) and small-for-gestational-age (SGA). Thus, having a better understanding of the expression and functions of miRNAs in human placenta during pregnancy and thereby developing novel drugs targeting the miRNAs could be a potentially promising method in the prevention and treatment of relevant diseases in future. Here, we summarize the current knowledge of the expression pattern and function regulation of miRNAs in human placental development and related diseases.

Mechanisms Controlling MicroRNA Expression in Tumor.

MicroRNAs (miRNAs) are widely present in many organisms and regulate the expression of genes in various biological processes such as cell differentiation, metabolism, and development. Numerous studies have shown that miRNAs are abnormally expressed in tumor tissues and are closely associated with tumorigenesis. MiRNA-based cancer gene therapy has consistently shown promising anti-tumor effects and is recognized as a new field in cancer treatment. So far, some clinical trials involving the treatment of malignancies have been carried out; however, studies of miRNA-based cancer gene therapy are still proceeding slowly. Therefore, furthering our understanding of the regulatory mechanisms of miRNA can bring substantial benefits to the development of miRNA-based gene therapy or other combination therapies and the clinical outcome of patients with cancer. Recent studies have revealed that the aberrant expression of miRNA in tumors is associated with promoter sequence mutation, epigenetic alteration, aberrant RNA modification, etc., showing the complexity of aberrant expression mechanisms of miRNA in tumors. In this paper, we systematically summarized the regulation mechanisms of miRNA expression in tumors, with the aim of providing assistance in the subsequent elucidation of the role of miRNA in tumorigenesis and the development of new strategies for tumor prevention and treatment.

MiRNA as a Potential Target for Multiple Myeloma Therapy-Current Knowledge and Perspectives.

Multiple myeloma (MM) is the second most common hematological malignancy. Despite the huge therapeutic progress thanks to the introduction of novel therapies, MM remains an incurable disease. Extensive research is currently ongoing to find new options. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post-transcriptional level. Aberrant expression of miRNAs in MM is common. Depending on their role in MM development, miRNAs have been reported as oncogenes and tumor suppressors. It was demonstrated that specific miRNA alterations using miRNA mimics or antagomirs can normalize the gene regulatory network and signaling pathways in the microenvironment and MM cells. These properties make miRNAs attractive targets in anti-myeloma therapy. However, only a few miRNA-based drugs have been entered into clinical trials. In this review, we discuss the role of the miRNAs in the pathogenesis of MM, their current status in preclinical/clinical trials, and the mechanisms by which miRNAs can theoretically achieve therapeutic benefit in MM treatment.

The miR-15a/16-1 and miR-15b/16-2 clusters regulate early B cell development by limiting IL-7 receptor expression.

MicroRNAs are small non-coding RNAs that have emerged as post-transcriptional regulators involved in development and function of different types of immune cells, and aberrant miRNA expression has often been linked to cancer. One prominent miRNA family in the latter setting is the miR-15 family, consisting of the three clusters miR-15a/16-1, miR-15b/16-2 and miR-497/195, which is best known for its prominent tumor suppressive role in chronic lymphocytic leukemia (CLL). However, little is known about the physiological role of the miR-15 family. In this study, we provide a comprehensive in vivo analysis of the physiological functions of miR-15a/16-1 and miR-15b/16-2, both of which are highly expressed in immune cells, in early B cell development. In particular, we report a previously unrecognized physiological function of the miR-15 family in restraining progenitor B cell expansion, as loss of both clusters induces an increase of the pro-B as well as pre-B cell compartments. Mechanistically, we find that the miR-15 family mediates its function through repression of at least two different types of target genes: First, we confirm that the miR-15 family suppresses several prominent cell cycle regulators such as Ccne1, Ccnd3 and Cdc25a also in vivo, thereby limiting the proliferation of progenitor B cells. Second, this is complemented by direct repression of the Il7r gene, which encodes the alpha chain of the IL-7 receptor (IL7R), one of the most critical growth factor receptors for early B cell development. In consequence, deletion of the miR-15a/16-1 and miR-15b/16-2 clusters stabilizes Il7r transcripts, resulting in enhanced IL7R surface expression. Consistently, our data show an increased activation of PI3K/AKT, a key signaling pathway downstream of the IL7R, which likely drives the progenitor B cell expansion we describe here. Thus, by deregulating a target gene network of cell cycle and signaling mediators, loss of the miR-15 family establishes a pro-proliferative milieu that manifests in an enlarged progenitor B cell pool.

Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tumors, characterized by a low rate of early diagnosis, strong invasiveness, and early metastasis. The abundant stromal cells, dense extracellular matrix, and lack of blood supply in PDAC limit the penetration of chemotherapeutic drugs, resulting in poor efficacy of the current treatment regimens. Cancer-associated fibroblasts (CAFs) are the major stromal cells in the tumor microenvironment. Tumor cells can secrete exosomes to promote the generation of activated CAFs, meanwhile exosomes secreted by CAFs help promote tumor progression. The aberrant expression of miRNAs in exosomes is involved in the interaction between tumor cells and CAFs, which provides the possibility for the application of exosomal miRNAs in the diagnosis and treatment of PDAC. The current article reviews the mechanism of exosomal miRNAs in the crosstalk between PDAC cells and CAFs in the tumor microenvironment, in order to improve the understanding of TME regulation and provide evidence for designing diagnostic and therapeutic targets against exosome miRNA in human PDAC.

Potential molecular mechanism in self-renewal is associated with miRNA dysregulation in sacral chordoma – A next-generation RNA sequencing study

BackgroundChordoma, the most frequent malignant primary spinal neoplasm, characterized by a high rate of recurrence, is an orphan disease where the clarification of the molecular oncogenesis would be crucial to developing new, effective therapies. Dysregulated expression of non-coding RNAs, especially microRNAs (miRNA) has a significant role in cancer development. MethodsNext-generation RNA sequencing (NGS) was used for the combinatorial analysis of mRNA-miRNA gene expression profiles in sacral chordoma and nucleus pulposus samples. Advanced bioinformatics workflow was applied to the data to predict miRNA-mRNA regulatory networks with altered activity in chordoma. ResultsA large set of significantly dysregulated miRNAs in chordoma and their differentially expressed target genes have been identified. Several molecular pathways related to tumorigenesis and the modulation of the immune system are predicted to be dysregulated due to aberrant miRNA expression in chordoma. We identified a gene set including key regulators of the Hippo pathway, which is targeted by differently expressed miRNAs, and validated their altered expression by RT-qPCR. These newly identified miRNA/RNA interactions are predicted to have a role in the self-renewal process of chordoma stem cells, which might sustain the high rate of recurrence for this tumor. ConclusionsOur results can significantly contribute to the designation of possible targets for the development of anti-chordoma therapies.

Multiomics to investigate the mechanisms contributing to repression of PTPRC and SOCS2 in pediatric T-ALL: Focus on miR-363-3p and promoter methylation.

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous and aggressive malignancy arising from T-cell precursors. MiRNAs are implicated in negative regulation of gene expression and when aberrantly expressed contribute to various cancer types, including T-ALL. Previously we demonstrated the oncogenic potential of miR-363-3p overexpression in a subgroup of T-ALL patients. Here, using combined proteomic and transcriptomic approaches, we show that miR-363-3p enhances cell growth of T-ALL in vitro via inhibition of PTPRC and SOCS2, which are implicated in repression of the JAK-STAT pathway. We propose that overexpression of miR-363-3p is a novel mechanism potentially contributing to overactivation of JAK-STAT pathway. Additionally, by combining the transcriptomic and methylation data of T-ALL patients, we show that promoter methylation may also contribute to downregulation of SOCS2 expression and thus potentially to JAK-STAT activation. In conclusion, we highlight aberrant miRNA expression and aberrant promoter methylation as mechanisms, alternative to mutations of JAK-STAT-related genes, which might lead to the upregulation of JAK-dependent signaling in T-ALL.

PLGA microspheres carrying miR-20a-5p improved intestinal epithelial barrier function in patients with Crohn’s disease through STAT3-mediated inhibition of Th17 differentiation

BackgroundRecent studies have shown that microRNAs (miRNAs) are aberrantly expressed in patients with Crohn's disease (CD). This suggests that the aberrant expression of miRNAs may contribute to the development of CD. Currently, the specific miRNAs involved in CD development have not been clearly identified. Therefore, we aimed to identify CD-associated miRNAs and explore their functions. MethodsmiRNA microarray analysis was performed to screen for differentially expressed miRNAs in colon tissues from normal controls (NC) and CD patients. The identified miRNAs were validated using quantitative real-time PCR (qPCR). The therapeutic roles of miR-20a-5p mimics via the delivery of poly(lactic-co-glycolic acid) microspheres (PLGA MSs) were further investigated in IL-10−/− mice with spontaneous chronic colitis that were used as a model of CD. The target genes of miR-20a-5p and the associated signaling pathways were identified through bioinformatic analysis and experimental verification of the interactions between the targets predicted by the algorithms and dysregulated mRNAs. ResultsThe analysis showed that miR-20a-5p was the most significantly downregulated miRNA in patients with CD. Treatment with PLGA MSs carrying miR-20a-5p significantly ameliorated the colitis, decreased mucosal inflammation, and improved epithelial barrier function. Bioinformatic analysis and experimental studies showed that miR-20a-5p inhibition enhanced Th17 differentiation and improved intestinal epithelial barrier function by targeting STAT3. ConclusionsDownregulation of miR-20a-5p improved the intestinal epithelial barrier function and prevented CD development through the STAT3/IL-17 signaling pathway. Therefore, the delivery of miR-20a-5p by PLGA MSs may serve as a potential therapeutic strategy for CD treatment.

PCDetection: PolyA-CRISPR/Cas12a-based miRNA detection without PAM restriction

MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate gene expression. The aberrant expression of miRNAs is related to many diseases. MiRNAs can serve as potential biomarkers for the prognosis and diagnosis of cancers and other human diseases. However, the short sequence and high sequence similarity of miRNAs impede detection. Herein, we propose a method to integrate polyA-tailing and CRISPR/Cas12a to amplify and detect all miRNAs with high specificity and sensitivity. PolyA-tailing enables efficient amplification of RNA and introduces a universal PAM sequence for Cas12a to unlock its PAM restriction. The CRISPR-Cas system guarantees the specific recognition of nucleic acid sequences with a single base mismatch. A limit of detection (LOD) as low as 50 fM was achieved. The practical application ability of polyA-CRISPR/Cas12a-based miRNA detection was validated by miRNA analyses in multiple cancer cell samples. With the increasing stability of RNA samples, low cost, excellent specificity, and sensitivity, this method demonstrates great potential to scale up to parallel diagnostic sets for miRNA-related disease.

Deciphering the Molecular Mechanism of Incurable Muscle Disease by a Novel Method for the Interpretation of miRNA Dysregulation.

It is now well-established that microRNA dysregulation is a hallmark of human diseases, and that aberrant expression of miRNA is not randomly associated with human pathologies but plays a causal role in the pathological process. Investigations of the molecular mechanism that links miRNA dysregulation to pathophysiology can therefore further the understanding of human diseases. The biological effect of miRNA is thought to be mediated principally by miRNA target genes. Consequently, the target genes of dysregulated miRNA serve as a proxy for the biological interpretation of miRNA dysregulation, which is performed by target gene pathway enrichment analysis. However, this method unfortunately often fails to provide testable hypotheses concerning disease mechanisms. In this paper, we describe a method for the interpretation of miRNA dysregulation, which is based on miRNA host genes rather than target genes. Using this approach, we have recently identified the perturbations of lipid metabolism, and cholesterol in particular, in Duchenne muscular dystrophy (DMD). The host gene-based interpretation of miRNA dysregulation therefore represents an attractive alternative method for the biological interpretation of miRNA dysregulation.

The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review.

Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.

Micro-RNA in Cholangiocarcinoma: Implications for Diagnosis, Prognosis, and Therapy

Bile-duct cancers (BDC) are a group of solid tumors arising from the biliary tree. Despite their classification as rare cancers, the incidence of BDC is increasing worldwide. Poor prognosis is a common feature of this type of cancer and is mainly determined by the following factors: late diagnosis, lack of effective therapeutic approaches, and resistance to conventional treatments. In the past few years, next-generation sequencing technologies has allowed us to study the genome, exome, and transcriptome of BDC deeper, revealing a previously underestimated class of RNA: the noncoding RNA (ncRNA). MicroRNAs (miRNAs) are small ncRNAs that play an important regulatory role in gene expression. The aberrant expression of miRNAs and their pivotal role as oncogenes or tumor suppressors in biliary carcinogenesis has been widely described in BDC. Due to their ability to regulate multiple gene networks, miRNAs are involved in all cancer hallmarks, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing/accessing vasculature, activating invasion and metastasis, reprogramming cellular metabolism, and avoiding immune destruction. Their use as diagnostic, prognostic, and predictive biomarkers has been widely explored in several human cancers, including BDC. Furthermore, miRNA-based therapeutic strategies are currently the subject of numerous clinical trials that are providing evidence of their efficacy as potent anticancer agents. In this review, we will provide a detailed update of miRNAs affecting BDC, discussing their regulatory function in processes underlying the molecular pathology of BDC. Finally, an overview of their potential use as biomarkers or therapeutic tools in BDC will be further addressed.

MiRNAs in Cardiac Myxoma: New Pathologic Findings for Potential Therapeutic Opportunities.

MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, contributing to all major cellular processes. The importance of miRNAs in cardiac development, heart function, and valvular heart disease has been shown in recent years, and aberrant expression of miRNA has been reported in various malignancies, such as gastric cancer and breast cancer. Different from other fields of investigation, the role of miRNAs in cardiac tumors still remains difficult to interpret due to the scarcity publications and a lack of narrative focus on this topic. In this article, we summarize the available evidence on miRNAs and cardiac myxomas and propose new pathways for future research. miRNAs play a part in modifying the expression of cardiac transcription factors (miR-335-5p), increasing cell cycle trigger factors (miR-126-3p), interfering with ceramide synthesis (miR-320a), inducing apoptosis (miR-634 and miR-122), suppressing production of interleukins (miR-217), and reducing cell proliferation (miR-218). As such, they have complex and interconnected roles. At present, the study of the complete mechanistic control of miRNA remains a crucial issue, as proper understanding of signaling pathways is essential for the forecasting of therapeutic implications. Other types of cardiac tumors still lack adequate investigation with regard to miRNA. Further research should aim at investigating the causal relationship between different miRNAs and cell overgrowth, considering both myxoma and other histological types of cardiac tumors. We hope that this review will help in understanding this fascinating molecular approach.

A Cell-Anchored and Self-Calibrated DNA Nanoplatform for in Situ Imaging and Quantification of Endogenous MicroRNA in Live Cells: Introducing Two Controls to Normalize the Sensing Signals

A Cell-Anchored and Self-Calibrated DNA Nanoplatform for in Situ Imaging and Quantification of Endogenous MicroRNA in Live Cells: Introducing Two Controls to Normalize the Sensing Signals

MicroRNA-129-1-3p Represses the Progression of Triple-Negative Breast Cancer by Targeting the GRIN2D Gene

The aberrant expression of miRNA is strongly linked to numerous stages of triple-negative breast cancer (TNBC) progression, and it plays an indispensable role in the process from tumor onset and progress to invasion and metastasis. In this study, we first transfected miR-129-1-3p mimics and inhibitor into MDA-MB-231 TNBC cells, respectively. Then, we assessed the pathological role of miR-129-1-3p in MDA-MB-231 cells. The results showed that miR-129-1-3p were successfully inserted into MDA-MB-231 cells. Besides, miR-129-1-3p could distinctively repress the growth, migration along with infiltration of MDA-MB-231 cells, which might be related to the inhibition of GRIN2D expression. Our results indicate that miR-129-1-3p was illustrated to serve as a tumor repressor via targeting GRIN2D in TNBC cells and highlight that the restoration of miR-129-1-3p might be a new treatment target for TNBC.

Diverse Roles and Targets of miRNA in the Pathogenesis of Testicular Germ Cell Tumour.

Simple SummaryTesticular germ cell tumour (TGCT) is the most common malignancy among young males in many parts of the world. Although it is highly remediable, treatments lead to long-term comorbidities, and therefore, it warrants a better prognosis. The presence of several risk loci in non-coding regions supports a functional role of miRNAs in TGCT development, and recent studies point to the emerging roles of miRNA and the complexity of miRNA-mediated gene regulation in TGCTs. miRNAs may act as oncogenes or tumour suppressors in TGCT by regulating targets involved in cell proliferation, apoptosis, and metastasis. Here, we summarise the gene regulation and function of miRNAs involved in TGCT pathogenesis.Testicular germ cell tumour (TGCT) is the most common cancer type among young adults in many parts of the world. Although the pathogenesis of TGCT is not well understood, the involvement of heritable components is evident, and the risk is polygenic. Genome-wide association studies have so far found 78 susceptibility loci for TGCT, and many of the loci are in non-coding regions indicating the involvement of non-coding RNAs in TGCT pathogenesis. MicroRNAs (miRNAs), a class of non-coding RNAs, have emerged as important gene regulators at the post-transcriptional level. They are crucial in controlling many cellular processes, such as proliferation, differentiation, and apoptosis, and an aberrant miRNA expression may contribute to the pathogenesis of several cancers, including TGCT. In support of this notion, several studies reported differential expression of miRNAs in TGCTs. We previously demonstrated that miRNAs were the most common group of small non-coding RNAs in TGCTs, and several functional studies of miRNAs in TGCTs suggest that they may act as either oncogene or tumour suppressors. Moreover, individual miRNA targets and downstream pathways in the context of TGCT development have been explored. In this review, we will focus on the diverse roles and targets of miRNAs in TGCT pathogenesis.