Previous studies demonstrated microRNA-185 (miR-185) as a tumor suppressive microRNA (miRNA) in various types of cancer. The current study aimed to verify this finding in hepatocellular carcinoma (HCC) and explored the downstream channel of miR-185-5p. We detected miR-185-5p and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) mRNA and protein levels by reverse transcription-quantitative PCR (RT-qPCR) and western blotting in HCC tissues and cell lines. Luciferase reporter assay proved the direct relationship between miR-185-5p and ROCK2. Cell migration and invasion were assessed via Transwell assay. miR-185-5p level was reduced in HCC tissues and cell lines. miR-185-5p overexpression impeded migration and invasion of HCC cells. Moreover, miR-185-5p directly targeted ROCK2 which was repressed by miR-185-5p in HCC. In addition, ROCK2 contributed to cell metastasis of HCC. In summary, miR-185-5p inhibited cell metastasis of HCC by suppressing ROCK2. The novel miR-185/ROCK2 axis shows potential in improving the therapies of HCC and enhancing HCC survival.

Background/Aims: The purpose of this study is to explore the expression characteristics of lncRNA NEAT1 in hepatocellular carcinoma (HCC) and the molecular mechanism of its regulation on sorafenib resistance. Materials and Methods: This experimental study was performed from June 2013 to June 2019. The level of NEAT1 was determined using RT-PCR in HCC and matched adjacent tissues from 79 HCC patients in Linyi central hospital. The patients were divided into two groups to compare their prognosis based on the median NEAT1 expressions as a cutoff value. HCC cell line HepG2 negative control (HepG2-NC), sorafenib-resistant HepG2 cells (HepG2-SR) were transfected with or without NEAT1 siRNA, followed by subsequent molecular analysis, to determine the function of NEAT1 on sorafenib resistance in HCC cells. The cell transcripts were determined by RNA-sequencing analysis. The binding site of the NEAT1 and microRNA-149-5p (miR-149-5p) was verified by luciferase assay. Results: We found that NEAT1 was significantly increased in HCC tissues. Furthermore, NEAT1 expressions were significantly associated with HCC prognosis and chemoresistance patterns against sorafenib. Subsequently, the sorafenib-resistant HCC cell lines, together with the controls, were used to determine the regulatory effect of NEAT1 on HCC cells' progression and sorafenib resistance. NEAT1 targets the miR-149-5p, and therefore, decrease the activity of sorafenib against HCC cells. NEAT1 functions were demonstrated to be triggered by the regulation of miR-149-5p/AKT1 axis. Conclusions: NEAT1/miR-149-5p/AKT1 pathway-based therapy might be a potential clinical application for HCC patients.

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Objectives: To assess the predictive function of miR-21 rs1292037 A>G polymorphism in survival and ischemia-reperfusion injury (IRI) in hepatocellular carcinoma (HCC) patients.

To find the effect of Paris saponin VII (PS VII)-mediated PI3K/AKT/MAPK signaling pathway on the sensitivity of ADR-resistant HepG2 cell (HepG2/ADR) cells to ADR.The proliferation inhibitory rates were detected by using MTT assay. Flow cytometry was employed to examine the intracellular accumulation of ADR. The expressions of drug-resistant genes (P-gp, MRP and BCRP) were detected by qRT-PCR, cell apoptosis by Annexin-V-FITC/PI staining, and the expressions of drug-resistance-related proteins, apoptosis-related proteins, and PI3K/AKT/MAPK pathway-related proteins were determined by Western blotting. HepG2/ADR and HepG2 cells treated with PS VII (0.88, 1.32, 1.98, and 2.97 μM) for 48 hours showed increased proliferation inhibitory rate in a dose-dependent manner. HepG2/ADR cells treated PS VII (0.88, 1.32, 1.98 μM) for 48 hours showed decreased IC50 of ADR. Compared with HepG2/ADR cells treated with ADR (5 nM), those treated with PS VII (≤1.98 μM) and ADR (5 nM) showed enhanced ADR accumulation, decreased drug-resistant gene expressions, increased cell apoptosis with unregulated Bax and cleaved caspase-3 and downregulated Bcl-2, as well as the inhibition of PI3K/AKT/MAPK pathway. Moreover, the combination of ADR (5 nM), PS VII (1.98 μM), and LY294002 (PI3K/AKT inhibitor, 20 μM)/SB203580 (P38 inhibitor, 20 μM) for 48 hours could further decreased the HepG2/ADR cell viability, but induced cell apoptosis, accompanying with the decreased expressions of drug-resistant genes. PS VII could downregulate the expressions of drug-resistance genes, increase intracellular accumulation of ADR, promote cell apoptosis, and enhance the sensitivity of HepG2/ADR cells to ADR via