lincRNA-RP11-564C4.6/microRNA-195回路调控肝癌转移的机制和意义

miRNA和lncRNA参与肿瘤的发生发展。miR-195在肝癌中普遍下调。前期研究我们发现miR-195抑制肝癌的转移；同时我们筛选出一个lncRNA——linc-R5是miR-195的潜在靶基因；我们进一步发现linc-R5在肝癌组织中表达上调，敲低linc-R5能有效抑制肝癌细胞的生长和迁移。更有意思的是，抑制linc-R5能提高miR-195的表达水平。这些结果提示linc-R5和 miR-195存在相互调节作用，并调控了肝癌的转移。我们拟以此基础开展：进一步鉴定linc-R5为miR-195的直接靶标；鉴定linc-R5对miR-195的调控作用及机制；验证linc-R5对肝癌侵袭转移的调控作用；构建linc-R5与miR-195间的信号通路，阐明该回路调控肝癌转移的机制。研究结果将加深人们对lncRNA和miRNA调控网络及其对肝癌转移作用的认识，为肝癌治疗提供新思路。

miRNA and lncRNA have been demonstrated to participate in tumor progression. miR-195 is downregulated frequently in hepatocellular carcinoma (HCC). In the pilot study, we found that miR-195 suppressed the metastasis of HCC; meanwhile, we predicted and verified one lncRNA, lincRNA-RP11-564C4.6 (linc-R5), as a potential target of miR-195. We further found that linc-R5 was upregulated in HCC tissues and knockdown of linc-R5 inhibited the growth and migration of HCC cells. Interestingly, silencing of linc-R5 enhanced the expression of miR-195 in HCC cells. With these findings as background, we plan: 1. to further identify linc-R5 as a direct target of miR-195. 2. to verify the regulation of miR-195 by linc-R5. 3. to verify the regulation and mechanism of linc-R5 on metastasis of HCC cells via evaluating growth, migration and invasion ability in vitro and metastasis in vivo. 4. to integrate pathways between linc-R5 and miR-195, and further to investigate the mechanism underlying the regulation of linc-R5/miR-195 regulatory loop in HCC metastasis. These results will expand our knowledge on the implication of miRNA and lncRNA in the metastasis of HCC, and provide novel targets for HCC therapy.