MicroRNA - Volume 12, Issue 2, 2023

Diagnosis and management of prostatic cancer (PCa) cases mainly rely on levels of prostatic- specific antigen (PSA) levels. In the majority of cases, rising of PCa is usually responsible for elevated PSA. However, a wide variety of prostatic abnormalities, such as benign prostatic hyperplasia and infection or inflammation of the prostatic glands, may also impact prostate levels. Due to the low specificity and sensitivity of the PSA test, elevated PSA levels can lead to unnecessary prostate biopsies or surgical interventions, constituting this diagnostic modality a controversial screening test. Therefore, the discovery of new non-invasive biomarkers, such as urinary miRNAs, could shed light on the optimal management and follow-up of patients with prostatic lesions. This study aims to evaluate the utility of urinary miRNAs as a new PCa prognostic biomarker, discovering its current limitations and proposing methods to overwhelm current challenges.

Background: Squamous cell carcinoma (SCC) is a non-melanoma skin cancer with several risk factors including age and sun exposure. The degree of histological differentiation is considered an independent predictor of recurrence, metastasis, and survival. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in regulating gene expression, culminating in the initiation and progression of multiple tumors. The aim of this study was to determine changes in miRNA expression as a result of the mode of differentiation in SCC. Methods: We analyzed 29 SCC samples that were separated by mode of differentiation into well (n=4), moderate (n=20) and poor (n=5). Of the 29 samples, five had matched normal tissues, which were used as controls. Total RNA was extracted using the RNeasy FFPE kit, and miRNAs were quantified using Qiagen MiRCURY LNA miRNA PCR Assays. Ten miRNAs (hsa-miR-21, hsa-miR-146b-3p, hsa-miR-155-5p, hsa-miR-451a, hsa-miR-196-5p, hsa-miR-221-5p, hsa-miR-375, hsa-miR-205-5p, hsa-let-7d-5p and hsa-miR-491-5p) that have been previously differentiated in cancer, were quantified. A fold regulation above 1 indicated upregulation and below 1, downregulation. Results: Hierarchical clustering showed that the miRNA expression profile in the moderately differentiated group was similar to the well-differentiated group. The miRNA with the greatest upregulation in the moderate group was hsa-miR-375, while in the well group, hsa-miR-491-5p showed the greatest downregulation. Conclusion: In conclusion, this study observed that the well and moderate groups had similar microRNA expression patterns compared to the poorly differentiated group. MicroRNA expression profiling may be used to better understand the factors underpinning mode of differentiation in SCC.

MicroRNAs (miRNAs) are short non-coding RNAs that repress or degrade mRNA targets to downregulate genes. In cancer occurrence, the expression of miRNAs is altered. Depending on the involvement of a certain miRNA in the pathogenetic growth of a tumor, It may be up or downregulated. The “oncogenic” action of miRNAs corresponds with upregulation, which leads to tumor proliferation and spread meanwhile the miRNAs that have been downregulated bring tumorsuppressive outcomes. Oncogenes and tumor suppressor genes are among the genes whose expression is under their control, demonstrating that classifying them solely as oncogenes or tumor suppressor genes alone is not only hindering but also incorrect. Apart from basic tumors, miRNAs may be found in nearly all human fluids and can be used for cancer diagnosis as well as clinical outcome prognostics and better response to treatment strategies. The overall variance of these tiny noncoding RNAs influences patient-specific pharmacokinetics and pharmacodynamics of anti-cancer medicines, driving a growing demand for personalized medicine. By now, microRNAs from tumor biopsies or blood are being widely investigated as substantial biomarkers for cancer in time diagnosis, prognosis, and, progression. With the rise of COVID-19, this paper also attempts to study recent research on miRNAs involved with deaths in lung cancer COVID patients. With the discovery of single nucleotide polymorphisms, personalized treatment via microRNAs has lately become a reality. The present review article describes the highlights of recent knowledge of miRNAs in various cancers, with a focus on miRNA translational applications as innovative potential diagnostic and prognostic indicators that expand person-to-person therapy options.

Non-alcoholic fatty liver disease (NAFLD), a metabolic-related disorder, is the most common cause of chronic liver disease which, if left untreated, can progress from simple steatosis to advanced fibrosis and eventually cirrhosis or hepatocellular carcinoma, which is the leading cause of hepatic damage globally. Currently available diagnostic modalities for NAFLD and hepatocellular carcinoma are mostly invasive and of limited precision. A liver biopsy is the most widely used diagnostic tool for hepatic disease. But due to its invasive procedure, it is not practicable for mass screening. Thus, noninvasive biomarkers are needed to diagnose NAFLD and HCC, monitor disease progression, and determine treatment response. Various studies indicated that serum miRNAs could serve as noninvasive biomarkers for both NAFLD and HCC diagnosis because of their association with different histological features of the disease. Although microRNAs are promising and clinically useful biomarkers for hepatic diseases, larger standardization procedures and studies are still required.

Being an integral part of the eukaryotic transcriptome, miRNAs are regarded as vital regulators of diverse developmental and physiological processes. Clearly, miRNA activity is kept in check by various regulatory mechanisms that control their biogenesis and decay pathways. With the increasing technical depth of RNA profiling technologies, novel insights have unravelled the spatial diversity exhibited by miRNAs inside a cell. Compartmentalization of miRNAs adds complexity to the regulatory circuits of miRNA expression, thereby providing superior control over the miRNA function. This review provides a bird’s eye view of miRNAs expressed in different subcellular locations, thus affecting the gene regulatory pathways therein. Occurrence of miRNAs in diverse intracellular locales also reveals various unconventional roles played by miRNAs in different cellular organelles and expands the scope of miRNA functions beyond their traditionally known repressive activities.

MicroRNAs are critical epigenetic regulators that can be used as diagnostic, prognostic, and therapeutic biomarkers for the treatment of various diseases, including gastrointestinal cancers, among a variety of cellular and molecular biomarkers. MiRNAs have also shown oncogenic or tumor suppressor roles in tumor tissue and other cell types. Studies showed that the dysregulation of miR-28 is involved in cell growth and metastasis of gastrointestinal cancers. MiR-28 plays a key role in controlling the physiological processes of cancer cells including growth and proliferation, migration, invasion, apoptosis, and metastasis. Therefore, miR-28 expression patterns can be used to distinguish patient subgroups. Based on the previous studies, miR-28 expression can be a suitable biomarker to detect tumor size and predict histological grade metastasis. In this review, we summarize the inhibitory effects of miR-28 as a metastasis suppressor in gastrointestinal cancers. miR-28 plays a role as a tumor suppressor in gastrointestinal cancers by regulating cancer cell growth, cell differentiation, angiogenesis, and metastasis. As a result, using it as a prognostic, diagnostic, and therapeutic biomarker in the treatment of gastrointestinal cancers can be a way to solve the problems in this field.

Background: Unbiased microRNA profiling of renal tissue and urinary extracellular vesicles (uEVs) from diabetic nephropathy (DN) subjects may unravel novel targets with diagnostic and therapeutic potential. Here we used the miRNA profile of uEVs and renal biopsies from DN subjects available on the GEO database. Methods: The miR expression profiles of kidney tissue (GSE51674) and urinary exosomes (GSE48318) from DN and control subjects were obtained by GEO2R tools from Gene Expression Omnibus (GEO) databases. Differentially expressed miRNAs in DN samples, relative to controls, were identified using a bioinformatic pipeline. Targets of miRs commonly regulated in both sample types were predicted by miRWalk, followed by functional gene enrichment analysis. Gene targets were identified by MiRTarBase, TargetScan and MiRDB. Results: Eight miRs, including let-7c, miR-10a, miR-10b and miR-181c, were significantly regulated in kidney tissue and uEVs in DN subjects versus controls. The top 10 significant pathways targeted by these miRs included TRAIL, EGFR, Proteoglycan syndecan, VEGF and Integrin Pathway. Gene target analysis by miRwalk upon validation using ShinyGO 70 targets with significant miRNA-mRNA interaction. Conclusion: In silico analysis showed that miRs targeting TRAIL and EGFR signaling are predominately regulated in uEVs and renal tissue of DN subjects. After wet-lab validation, the identified miRstarget pairs may be explored for their diagnostic and/or therapeutic potential in diabetic nephropathy.

Background: Chronic kidney disease of unknown etiology (CKDu) is reported among male paddy farmers in the dry zone of Sri Lanka. The exact cause of this disease remains undetermined. Genetic susceptibility is identified as a major risk factor for CKDu Objectives: In this study, small urinary RNAs were characterized in CKDu patients, healthy endemic and non-endemic controls. Differently expressed urinary miRNAs and their associated pathways were identified in the study population. Methods: Healthy and diseased male volunteers (n = 9) were recruited from Girandurukotte (endemic) and Mawanella (non-endemic) districts. Urinary small RNAs were purified and sequenced using Illumina MiSeqTM. The sequence trace files were assembled and analyzed. Differentially ex-pressed miRNAs among these three groups were identified and pathway analysis was conducted. Results: The urine samples contained 130,623 sequence reads identified as non-coding RNAs, PIWI-interacting RNAs (piRNA), and miRNAs. Approximately four percent of the total small RNA reads represented miRNA, and 29% represented piRNA. A total of 409 miRNA species were ex-pressed in urine. Interestingly, both diseased and endemic controls population showed significantly low expression of miRNA and piRNA. Regardless of the health status, the endemic population ex-pressed significantly low levels of miR-10a, miR-21, miR-148a, and miR-30a which have been linked with several environmental toxins Conclusion: Significant downregulation of miRNA and piRNA expression in both diseased and healthy endemic samples indicates an epigenetic regulation of CKDu involving genetic and environmental interaction. Further studies of specific miRNA species are required to develop a miRNA panel to identify individuals susceptible to CKDu.