Downregulation of miR-193a-3p is involved in the pathogenesis of hepatocellular carcinoma by targeting CCND1

Abstract

Background Hepatocellular carcinoma (HCC) is the second-highest cause of malignancy-related death worldwide, and many physiological and pathological processes, including cancer, are regulated by microRNAs (miRNAs). miR-193a-3p is an anti-oncogene that plays an important part in health and disease biology by interacting with specific targets and signals. Methods In vitro assays were performed to explore the influences of miR-193a-3p on the propagation and apoptosis of HCC cells. The sequencing data for HCC were obtained from The Cancer Genome Atlas (TCGA), and the expression levels of miR-193a-3p in HCC and non-HCC tissues were calculated. The differential expression of miR-193a-3p in HCC was presented as standardized mean difference (SMD) with 95% confidence intervals (CIs) in Stata SE. The impact of miR-193a-3p on the prognoses of HCC patients was determined by survival analysis. The potential targets of miR-193a-3p were then predicted using miRWalk 2.0 and subjected to enrichment analyses, including Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Protein-Protein Interaction (PPI) network analysis. The interaction between miR-193a-3p and one predicted target, Cyclin D1 (CCND1), was verified by dual luciferase reporter assays and Pearson correlation analysis. Results MiR-193a-3p inhibited the propagation and facilitated the apoptosis of HCC cells in vitro. The pooled SMD indicated that miR-193a-3p had a low level of expression in HCC (SMD: −0.88, 95% CI [−2.36 −0.59]). Also, HCC patients with a higher level of miR-193a-3p expression tended to have a favorable overall survival (OS: HR = 0.7, 95% CI [0.43–1.13], P = 0.14). For the KEGG pathway analysis, the most related pathway was “proteoglycans in cancer”, while the most enriched GO term was “protein binding”. The dual luciferase reporter assays demonstrated the direct interaction between miR-193a-3p and CCND1, and the Pearson correlation analysis suggested that miR-193a-3p was negatively correlated with CCND1 in HCC tissues (R = − 0.154, P = 0.002). Conclusion miR-193a-3p could suppress proliferation and promote apoptosis by targeting CCND1 in HCC cells. Further, miR-193a-3p can be used as a promising biomarker for the diagnosis and treatment of HCC in the future.

Upregulation of microRNA miR-141-3p and its prospective targets in endometrial carcinoma: a comprehensive study

“…We conducted a comprehensive evaluation of the data from the three resources (in-house RT-qPCR, miRNA-seq and miRNA chips) by performing an integrated analysis using Stata software version 15.1 (TX, USA) to calculate the standard mean difference (SMD) and to draw a summary receiver operating characteristic (sROC) curve [27][28][29]. Continuous variables were assessed by SMD with a 95% confidence interval (95%CI), and heterogeneity was evaluated by the chi-squared-based Q-test and the I 2 statistics value.…”

miR-193a-3p Promotes the Invasion, Migration, and Mesenchymal Transition in Glioma through Regulating BTRC

“…Takahashi et al reported that miR-193a-3p is specifically downregulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer [ 36 ]. miR-193a-3p could suppress proliferation and promote apoptosis by targeting cyclin D1 in hepatocellular carcinoma cells [ 37 ]. LncRNA of UCA1 functions as an oncogene in NSCLC, acting mechanistically by upregulating ERBB4 in part through the sponging of tumor suppressor miR-193a-3p [ 38 ].…”

Restoration of miR-193a expression is tumor-suppressive in MYC amplified Group 3 medulloblastoma

“…MicroRNAs, which are natural inhibitors of multiple genes, are attractive therapeutic molecules provided they are exclusively tumor-suppressive or oncogenic. MiR-193a has been reported to be tumor-suppressive in multiple cancers by downregulating several oncogenic targets [45][46][47][48]. Hence it is potentially a good therapeutic small molecule.…”