miR‑642 serves as a tumor suppressor in hepatocellular carcinoma by regulating SEMA4C and p38 MAPK signaling pathway

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and high risk. Study of the role and mechanism of miRNAs are a hot spot of research providing new treatment ideas in malignant tumors. The effect of miR-642a on HCC progression and the underlying molecular mechanism were investigated. Expression of miR-642a and SEMA4C was measured by western blot analysis and RT-PCR. miR-642a expression was elevated while SEMA4C expression was attenuated in HCC tissues and cells. Results of luciferase reporter and western blot analyses show that miR-642a modulated SEMA4C expression by binding to its 3'UTR. Moreover, miR-642a negatively regulated SEMA4C expression. HCC cell migration and invasion was tested by Transwell assays. The findings revealed that the number of migrated and invaded cells were reduced by miR-642a mimic and raised by miR-642a inhibitor, indicating that miR-642a showed a suppression effect on HCC cell migration and invasion. Additionally, the migration and invasion of HCC cells were inhibited by SEMA4C siRNA, and SEMA4C reversed miR-642a effect on HCC migration and invasion. Furthermore, p38 MAPK signaling pathway was proven to be inhibited by miR-642a mimic, whereas facilitated by miR-642a inhibitor and SEMA4C siRNA could overturn the promotion effect of miR-642a inhibitor. Briefly, miR-642a targeted SEMA4C to repress HCC cell migration and invasion through p38 MAPK signaling pathway providing a new strategy for treatment of HCC patients.

Circ_0091579 exerts an oncogenic role in hepatocellular carcinoma via mediating miR-136-5p/TRIM27

“…Based on the expression pattern of miR-136-5p in HCC, its interacted mRNAs should exhibit high expression in HCC. Through bioinformatics prediction and literature review, we focused on six candidate mRNAs, including PAX6 [ 29 ], SEMA4C [ 30 ], ROCK1 [ 31 ], FZD4 [ 32 ], TRIM27 [ 20 ], and ABCC12 [ 33 ]. MiR-136-5p overexpression reduced the levels of FZD4, TRIM27, and ABCC12 in both HCC cell lines ( Supplementary Fig.…”

MicroRNA Expression Signatures in Clear Cell Renal Cell Carcinoma: High-Throughput Searching for Key miRNA Markers in Patients from the Volga-Ural Region of Eurasian Continent

“…miRNA-642 downregulation reduced the cell viability in bladder cancer cell lines, with different cisplatin sensitivity [ 27 ]. It was described recently that miRNA-642 could act as a tumor suppressor through regulating p38 MAPK signaling pathway in hepatocellular carcinoma [ 28 ]. In addition, miRNA-642 served as a tumor suppressor in prostate cancer.…”

Extracellular vesicle miRNAs in breast milk of obese mothers

“…Especially, women with obesity are at increased risk of breast cancers, therefore, differentially expressed miRNAs of bEVs in mothers with obesity could be the molecules that either help us to predict breast cancer occurrence or trigger cancer development. In fact, previous studies demonstrated that downregulated miRNAs in bEV of mothers with obesity, such as miR-630 and miR-642 , suppress cancers ( 61 , 62 ). miR-548j-3p , upregulated in mothers with obesity, plays a role as a metastasis promoter in breast cancer ( 63 ).…”