MicroRNA-506 suppresses invasiveness and metastasis of human hepatocellular carcinoma cells by targeting IL8.

MicroRNAs (miRNAs) have been reported to be involved in tumor metastasis. In this study, we investigated the function of miR-506 in the metastasis of human hepatocellular carcinoma (HCC). We found that miR-506 is significantly downregulated in the primary tissue of metastatic HCC and in highly metastatic HCC cell lines. Overexpression of miR-506 suppressed HCC cell migration, invasion, and metastasis both in vitro and in vivo. Furthermore, miR-506 was found to specifically target the 3' untranslated region (3'-UTR) of interleukin 8 (IL8) mRNA. Spearman's correlation analysis revealed that miR-506 expression inversely correlated with IL8 mRNA and protein expression in HCC tissue samples. IL8 treatment reversed miR-506-induced suppression of HCC cell migration and invasiveness. Thus, miR-506 acts as a tumor suppressor that may inhibit the migration, invasiveness, and metastasis of HCC cells by targeting IL8.

Overexpression of RAS-Association Domain Family 6 (RASSF6) Inhibits Proliferation and Tumorigenesis in Hepatocellular Carcinoma Cells.

Ras-association domain family 6 (RASSF6), a member of the RASSF family, is frequently downregulated in various types of cancer. However, the roles of RASSF6 in human hepatocellular carcinoma (HCC) are still unclear. In this study, we investigated the biological functions and related molecular mechanisms in HCC. Our results found that RASSF6 is expressed in low amounts in HCC tissues and cell lines. Overexpression of RASSF6 obviously inhibited the proliferation, invasion, and EMT process in HCC cells. Furthermore, overexpression of RASFF6 greatly downregulated the protein levels of phosphorylated focal adhesion kinase (FAK), MMP-2, and MMP-9 in HepG2 cells. Last, overexpression of RASFF6 significantly attenuated tumor growth in Balb/c nude mice. In conclusion, the present study revealed that RASFF6 can inhibit the proliferation, invasion, and migration of HCC cells both in vivo and in vitro. These inhibitory effects are through suppressing FAK phosphorylation, leading to decreased MMP-2/9 expression. RASFF6 is therefore a potential therapeutic target for treating HCC.

[Expression of CD90/EpCAM/CD24 in hepatocellular carcinoma cell lines at various stages of differentiation].

OBJECTIVE: To confirm the malignant phenotype of hepatocarcinoma cell (HCC) lines at various stages of differentiation (MHCC97L, MHCC97H and HCCLM3) and to explore their expression levels of cancer stem cell (CSC) markers. METHODS: The invasive and proliferative properties of each HCC line were assessed by transwell assay and the Cell Counting Kit-8 (CCK-8) colorimetric assay. Sensitivity to chemotherapy was assessed by treatment with oxaliplatin and determination of the half inhibitory concentration (IC50). The expression of CD90, EpCAM and CD24 was measured by flow cytometry. RESULTS: The number of cells that migrated through the invasion assay membrane were significantly different between the three HCC lines: HCCLM3 (30.57 +/- 8.95) more than MHCC97H (21.33 +/- 4.17) more than HCC97L (9.33 +/- 3.85), P less than 0.01. The IC50 was significantly different between the three HCC lines: HCCLM3 (36.57 +/- 6.95) mumol/L more than MHCC97H (26.35+/-3.88) mumol/L more than MHCC97L (17.68 +/- 3.25) mumol/L. The CSC marker with the highest expression on all three HCC lines was CD90 (HCCLM3: 0.92% +/- 0.21%, MHCC97H: 1.98% +/- 0.23%, and MHCC97L: 2.55% +/- 0.34%), followed by EpCAM (2.11% +/- 0.32%, 3.23% +/- 0.18%, and 4.38% +/-0.49%, respectively), and CD24 as the lowest (0.68% +/- 0.37%, 1.22% +/- 0.26%, and 1.36% +/- 0.24%, respectively). CONCLUSION: Higher expression of CSC markers on HCC lines is associated with a stronger invasive ability and higher sensitivity to chemotherapy.