Linc-AATBC对膀胱癌细胞自噬、凋亡的重要调控作用及分子机制研究

项目名称： Linc-AATBC对膀胱癌细胞自噬、凋亡的重要调控作用及分子机制研究

项目编号： No.81472388

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 谢文练

作者单位： 中山大学

项目金额： 80万元

中文摘要： 长链基因间非编码RNA在肿瘤中起着癌基因/抑癌基因功能，自噬与凋亡在肿瘤进展中亦有重要作用。我们预实验发现linc-AATBC在膀胱癌中高表达，沉默linc-AATBC能使膀胱癌细胞自噬活性增强、凋亡增加，Akt-TSC1/2-Rheb-mTOR通路的关键因子Akt、mTOR活性降低；应用3-MA抑制自噬后，沉默linc-AATBC所导致的肿瘤细胞凋亡减少，提示linc-AATBC通过抑制自噬减少肿瘤细胞的凋亡。既往文献及生物信息学分析提示：miR-7在恶性肿瘤中起抑癌基因功能，PI3K催化亚基PIK3CD的3'UTR与linc-AATBC均有多个miR-7结合位点。基于以上基础，本项目将研究：linc-AATBC在膀胱癌中通过吸附性清除miR-7，增加PIK3CD表达，激活Akt-TSC1/2-Rheb-mTOR通路，然后通过抑制自噬减少肿瘤细胞凋亡，在膀胱癌中发挥癌基因功能的分子机制。

中文关键词： 长链基因间非编码RNA；膀胱癌；自噬；凋亡

英文摘要： Long intergenic non-coding RNAs (lincRNAs) act as oncogenes or tumor suppressor genes in human cancer. Autophagy and apoptosis also play important roles in tumor progression. In our preliminary study, we found linc-AATBC was overexpressed in bladder cancer. After silence of linc-AATBC, the autophagic activity of bladder cancer cells was enhanced, apoptotic cells were increased and the lower activity of Akt and mTOR was detected, which are key factors in Akt-TSC1/2-Rheb-mTOR pathway. After suppression of autophagy by 3-MA, apoptotic cells resulted from the silencing of linc-AATBC were decreased. It suggested that linc-AATBC could decrease the apoptosis of cancer cells by inhibiting autophagy. Previous studies suggested that miR-7 acts as a tumor suppressor gene. Bioinformatic analysis illustrated linc-AATBC and the 3'UTR of PIK3CD, which is a catalytic subunit of PI3K, share several miR-7 binding sites. Based on the above basis, we aim to study the role of linc-AATBC in bladder cancer and the molecular mechanisms including that linc-AATBC increases the expression of PIK3CD by absorptively removing miR-7, activates the Akt-TSC1/2-Rheb-mTOR pathway and decreases the apoptosis of cancer cells via suppressing autophagy.

英文关键词： lincRNA;bladder cancer;autophagy;apoptosis