MicroRNA-500a Promotes the Progression of Hepatocellular Carcinoma by Post-Transcriptionally Targeting BID

Abstract

Background/Aims: Hepatocellular carcinoma (HCC) is one of the most common human malignant diseases in the world, and the mechanisms underlying HCC carcinogenesis and progression need further investigation. MicroRNAs play important roles in the development of cancer, and miR-500a is suggested to be deregulated in some types of cancer. However, the underlying molecular mechanisms of miR-500a in HCC remain unknown. Methods: The expression of miR-500a in HCC was analyzed in The Cancer Genome Atlas (TCGA) database and examined in 33 pairs of HCC tissues and matched nontumor tissues. The correlation between miR-500a expression and prognosis of HCC patients was analyzed from the survival data in TCGA. The mechanism of miR-500a upregulation in HCC was detected using chromatin immunoprecipitation-quantitative real-time PCR. The roles of miR-500a in HCC development were examined using a cell counting kit-8 assay in vitro and growth of transplanted tumors in nude mice in vivo. Apoptosis of HCC was detected using Annexin V/propidium iodide staining. The expression of BH3-interacting death agonist (BID) protein was examined using western blot analysis. Results: miR-500a expression was upregulated in HCC tissues, and high miR-500a expression was significantly correlated with the poor prognosis of HCC patients. Histone modifications in the promoter region of miR-500a may be responsible for its increased expression. Inhibition of miR-500a in HCC cell lines significantly promoted apoptosis, as well as inhibiting the proliferation of HCC cells and growth of transplanted tumors in nude mice. miR-500a directly targeted the 3′ untranslated region of BID mRNA, and inhibition of miR-500a-promoted apoptosis was almost completely abolished by the administration of ABT-199 via the BID-mitochondria pathway. Conclusion: Our results suggest that histone modifications in the promoter region of miR-500a may be responsible for the increased expression of miR-500a in HCC, which promotes cancer progression by targeting BID, indicating that miR-500a may be a potential prognostic predictor and therapeutic target for HCC patients.

lncRNA NEAT1 regulates gastric carcinoma cell proliferation, invasion and apoptosis via the miR‑500a‑3p/XBP‑1 axis

“…The results indicated that the lncRNA NEAT1 might suppress the development of gastric cancer by promoting gastric cancer cell apoptosis. Previous studies have identified miR-500a-3p as a potential prognostic predictor in certain types of cancer, including hepatocellular carcinoma and glioblastoma, and have reported an association between miR-500a and TNM stage in lung cancer and conjunctival malignant melanoma (32)(33)(34)(35). Other studies have reported that XBP-1 is closely associated with clinical outcome (36,37).…”

FXR1 promotes the malignant biological behavior of glioma cells via stabilizing MIR17HG

“…Aberrant expression of TAL1 in later stages of T-cell development is associated with the development of T-cell acute lymphoblastic leukemia (T-ALL) [22]. By binding to the 3’UTR of mRNAs, miRNAs can either suppress the expression of downstream target genes at transcriptional level or degration target mRNA [23, 24]. Using bioinformatic software Targetscan (http://www.targetscan.org/), we predicted TAL1 as a presumed target of miR-346 and miR-425-5p, which indicates that miR-346 and miR-425-5p may be functional in glioma through binding to TAL1.…”

The oncogenic role of microRNA‑500a in colorectal cancer

“…The function of miR-500a has been studied in hepatocellular carcinoma (HCC) (15), and it has been determined that miR-500a promotes the progression of HCC by post-transcriptionally targeting the BH3 interacting domain death agonist gene. In addition, miR-500a expression is upregulated in HCC tissues, and high miR-500a expression is significantly correlated with poor prognosis of patients with HCC (15). However, the function of miR-500a in CRC remains unknown.…”