DNA Methylation-regulated miR-193a-3p Dictates Resistance of Hepatocellular Carcinoma to 5-Fluorouracil via Repression of SRSF2 Expression

Abstract

Background: Chemoresistance prevents effective therapy of hepatocellular carcinoma (HCC). Results: Genomic and mechanistic studies suggested the role of miR-193a-3p via SRSF2 mediates up-regulation of the proapoptotic splicing form of caspase 2 in HCC 5-FU resistance. Conclusion:We identify a novel molecular mechanism underlying 5-FU resistance in HCC. Significance: These molecular events identified provide a set of prognostic markers for future rational 5-FU therapy in HCC.

miR-193a-3p Functions as a Tumor Suppressor in Lung Cancer by Down-regulating ERBB4

“…These results suggest that miR-193a-3p may be involved in the pathogenesis of lung cancer as a tumor suppressor. Indeed, miR193a-3p has been reported in many studies to be down-regulated in cancers (31,33,38,52,54,55). On the other hand, it is well known that a single miRNA can target multiple genes, whereas multiple miRNAs can target a single gene.…”

Detection of Circulating miRNA Levels in Schizophrenia

“…The down-regulation of these genes by miRNAs may disturb neuronal function, leading in turn to dysfunction of the neural circuits. Interestingly, both the upstream regions of miR-130b and miR-193a-3p genes contain a CpG island, which can be regulated by DNA methylation and histone modification (40,41). These two miRNAs may contribute to the pathogenesis of schizophrenia via epigenetic pathways, although additional studies are needed to clarify the precise mechanism by which miR-130b and miR-193a-3p may play a crucial role in developing schizophrenia.…”

Methylxanthines Increase Expression of the Splicing Factor SRSF2 by Regulating Multiple Post-transcriptional Mechanisms

“…Only two of these have been previously validated: miR-183-5p in stress response (47) and miR-193a-3p in cancer drug resistance (48). We now show that caffeine can regulate a subset of miRs, including miR-183-5p, which targets A1 and possibly all GD members (Fig.…”

“…MicroRNA-mediated translation repression has recently been suggested as a mechanism for SRSF2 regulation in amygdala during acute stress (miR-183-5p) (47) and in hepatocellular carcinoma during the acquisition of drug resistance (miR-193a-5p) (48).…”