Lv Wenjie, Wang Lei, Lu Jianhua, Mu Jiasheng, Liu Yingbin, Dong Ping
Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
Chem Biol Drug Des. 2015 Oct;86(4):656-62. doi: 10.1111/cbdd.12533. Epub 2015 May 11.
Human gallbladder cancer is a rare malignancy disease but having poor prognosis over the world. Previous studies have put forward that PTEN is a tumour suppressor in regulating many cellular processes, similar activities have been observed for its mammal homologue TPTE2. In this study, we attempted to unravel the underlying mechanistic basis of the role of TPTE2 and its pseudogene TPTE2P1 in gallbladder cancer. We employed lentivirus-mediated RNA interference as an efficient tool to silence endogenous TPTE2P1 transcription in the gallbladder cancer cell line GBC-SD/M. The effects of TPTE2P1 on cell migration and invasion were determined by transwell assays. We figured that depletion of TPTE2P1 remarkably inhibited gallbladder cancer cell migration and invasion capacity in vitro and elevated the expression of β-catenin via epithelial-mesenchymal transition signalling. Our findings revealed the functional role of TPTE2P1 in human gallbladder cancer and suggested that TPTE2P1 could serve as a promising therapeutic target and a palliation option in human gallbladder cancer.
人类胆囊癌是一种罕见的恶性疾病,在全球范围内预后较差。先前的研究提出,PTEN是一种在调节许多细胞过程中起作用的肿瘤抑制因子,其哺乳动物同源物TPTE2也观察到了类似的活性。在本研究中,我们试图揭示TPTE2及其假基因TPTE2P1在胆囊癌中作用的潜在机制基础。我们采用慢病毒介导的RNA干扰作为一种有效工具,沉默胆囊癌细胞系GBC-SD/M中的内源性TPTE2P1转录。通过Transwell实验确定TPTE2P1对细胞迁移和侵袭的影响。我们发现,TPTE2P1的缺失显著抑制了胆囊癌细胞在体外的迁移和侵袭能力,并通过上皮-间质转化信号通路提高了β-连环蛋白的表达。我们的研究结果揭示了TPTE2P1在人类胆囊癌中的功能作用,并表明TPTE2P1有望成为人类胆囊癌的治疗靶点和缓解选择。