MicroRNA-22-3p and MicroRNA-149-5p Inhibit Human Hepatocellular Carcinoma Cell Growth and Metastasis Properties by Regulating Methylenetetrahydrofolate Reductase

Abstract

microRNAs are small endogenous noncoding RNAs that have emerged as key negative regulators that target gene expression through RISC. Our previous study showed that the methylenetetrahydrofolate reductase gene (MTHFR) plays a key role in one carbon metabolism, which is downregulated by miR-22-3p and miR-149-5p, and that it could exert a potential anti-cancer effect. Whether miR-22-3p/miR-149-5p can regulate MTHFR to exert anti-cancer effects has become the focus of our research. Normal (HL-7702 cells) and cancerous (QGY-7703/HepG2 cells) human hepatocellular cells were transfected with 100 nM hsa-miR-22-3p/hsa-miR-149-5p mimic or controls. After 24, 48, and 72 h, cell proliferation ability was tested using CCK-8. The changes in MTHFR expression at both the transcriptional and translational levels were determined by RT-qPCR and Western blotting, respectively. Cancerous cell invasion and migration ability were confirmed by means of a transwell assay. We found that ectopic miR-22-3p/miR-149-5p inhibits hepatocellular carcinoma cell proliferation but does not inhibit normal human hepatocyte proliferation. The transfection of ectopic miR-22-3p/miR-149-5p downregulated the MTHFR expression in QGY-7703 and HepG2 but not in HL-7702. QGY-7703 and HepG2 migration and invasion were inhibited by ectopic miR-22-3p/miR-149-5p. Additionally, we found that ectopic miR-22-3p/miR-149-5p significantly increased the expression of TP53INP1 and PDCD4 in QGY-7703. The results of the study suggest that miRNA-22-3p and miRNA-149-5p inhibit tumor growth and metastasis properties may be by regulating MTHFR and that they exert anticancer effects in hepatocellular carcinoma cells.

Roles of Exosomes in Chronic Rhinosinusitis: A Systematic Review

“…The potential therapeutic role of miR-22-3p was widely investigated and confirmed in the regulation of angiogenesis by targeting VE-cadherin [ 35 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ].VE-cadherin is a component of adherents of vascular endothelial cells, which controls vascular permeability and inhibits unrestrained vascular growth [ 96 ]. The decreased expression of VE-cadherin is associated with endothelial paracellular permeability, which is observed in CRSwNP [ 97 ].…”

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

“…Studies conducted in various cancer types, including thyroid cancer, reported that miR-324-5p is generally up-regulated [40]. Several authors investigated the biological role of miR-22-3p, and described it as a tumor suppressor miRNA [41][42][43]. In cervical squamous cell carcinoma, miR-22-3p downregulation has been associated with metastatic tumor progression [44]; the biological functions of miR-22-3p in the context of RAS-mutant thyroid tumors has not been investigated.…”