MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma.

Some microRNAs (miRNAs) have been implicated in hepatocellular carcinoma (HCC) development and progression. However, the roles and mechanisms of several miRNAs in HCC remain poorly understood. Here, we report that miR-379-5p, which is down-regulated in HCC tissues and cell lines, is associated with advanced TNM stage and metastasis in HCC. The ectopic overexpression of miR-379-5p inhibited HCC cell migration, invasion, epithelial-to-mesenchymal transition (EMT) and metastasis both in vitro and in vivo. Conversely, miR-379 knockdown increased migration, invasion and EMT in HCC cells. Moreover, miR-379-5p exerted this function by directly targeting focal adhesion kinase (FAK) 3'-UTR and repressing FAK expression, thus leading to suppression of AKT signaling. Furthermore, the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression. In clinical samples of HCC, miR-379-5p negatively correlated with FAK, which was up-regulated in HCC. Taken together, our findings highlight the important role of miR-379-5p in regulating the EMT and metastasis of HCC by targeting FAK/AKT signaling, suggesting that miR-379-5p may represent a novel potential therapeutic target and prognostic marker for HCC.

Down-regulation of Gli-1 inhibits hepatocellular carcinoma cell migration and invasion.

Glioma-associated oncogene homolog-1 (Gli-1) is considered a marker of Hedgehog pathway activation and is associated with the progression of several cancers. We have previously reported that Gli-1 was correlated with invasion and metastasis in hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of Gli-1 in HCC invasion are unclear. In this study, we found that small interfering RNA mediated down-regulation of Gli-1 expression significantly suppressed adhesion, motility, migration, and invasion of both SMMC-7721 and SK-Hep1 cells. Furthermore, down-regulation of Gli-1 significantly reduced expressions and activities of both matrix metalloproteinase (MMP)-2 and MMP-9. In addition, we found that down-regulation of Gli-1 resulted in up-regulation of E-cadherin and concomitant down-regulation of Snail and Vimentin, consistent with inhibition of epithelial-mesenchymal transition (EMT). Taken together, our results suggest that down-regulation of Gli-1 suppresses HCC cell migration and invasion likely through inhibiting expressions and activations of MMP-2, 9 and blocking EMT.

Excision repair cross complementation group 1 polymorphisms and lung cancer risk: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 (ERCC1) enzyme and lung cancer risk in diverse populations but with conflicting results. By pooling the relatively small samples in each study, it is possible to perform a meta-analysis of the evidence by rigorous methods.</p><p><b>METHODS</b>Embase, Ovid, Medline and Chinese National Knowledge Infrastructure were searched. Additional studies were identified from references in original studies or review articles. Articles meeting the inclusion criteria were reviewed systematically, and the reported data were aggregated using the statistical techniques of meta-analysis.</p><p><b>RESULTS</b>We found 3810 cases with lung cancer and 4332 controls from seven eligible studies. T19007C polymorphism showed no significant effect on lung cancer risk (C allele vs. T allele: odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.80 - 1.04; CC vs. TT: OR = 0.76, 95%CI = 0.56 - 1.02; CC vs. (CT + TT): OR = 0.96, 95%CI = 0.84 - 1.10). Similarly, there was no significant main effects for T19007C polymorphism on lung cancer risk when stratified analyses by ethnicity (Chinese or Caucasian). No significant association was found between C8092A polymorphism (3060 patients and 2729 controls) and the risk of lung cancer (A allele vs. C allele: OR = 1.03, 95%CI = 0.95 - 1.11; AA vs. CC: OR = 1.08, 95%CI = 0.88 - 1.33; AA vs. (AC + CC): OR = 1.08, 95%CI = 0.88 - 1.31).</p><p><b>CONCLUSION</b>We found little evidence of an association between the T1900C or C8092A polymorphisms of ERCC 1 and the risk of lung cancer in Caucasian or Han Chinese people.</p>

Octreotide inhibits growth of colonic cancer SW480 cells by modulating the Wnt/P-catenin pathway.

Somatostatin can suppress the growth of various tumor cells including colonic cancer. Activated Wnt/ beta-catenin signaling pathway plays a critical role in tumorgenesis and development of colorectal cancer. However, the effect of somatostatin on Wnt/beta-catenin signaling pathway remains unknown. Thus, we investigated the effect of octreotide on Wnt/beta-catenin signaling pathway in human colonic cancer cell SW480. The results of 3-(4,5-imethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and flow cytometric assays showed that octreotide inhibited growth, induced apoptosis and arrested the G1 cell cycle of SW480 cells in a dose-dependent manner. We demonstrated that octreotide significally up-regulated and down-regulated 13 genes and 17 genes in Wnt/beta-catenin signaling using microarray, respectively. Furthermore, as evidenced by western blot, beta-catenin protein level decreased, whereas phosphorylated beta-catenin protein level increased under octreotide. The present study reveals that octreotide can inhibit human colonic cancer cell growth through inhibition of Wnt/beta-catenin signaling pathway.