ascl2 knockdown results in tumor growth arrest by mirna-302b-related inhibition of colon cancer progenitor cellsascl2击倒导致肿瘤生长逮捕microrna的- 302 b -抑制结肠癌祖细胞有关.pdfVIP

Ascl2 Knockdown Results in Tumor Growth Arrest by miRNA-302b-Related Inhibition of Colon Cancer Progenitor Cells 1 1 1 1 1 1 1 Rong Zhu , Yongtao Yang , Yin Tian , Jianying Bai , Xin Zhang , Xiaohuan Li , Zhihong Peng , 1 1 1 1 1 2 2 Yonghong He , Lei Chen , Qiong Pan , Dianchun Fang , Wensheng Chen , Chen Qian , Xiuwu Bian , Rongquan Wang1* 1 Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China, 2 Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China Abstract Background: Achaete scute-like 2 (Ascl2), a basic helix-loop-helix (bHLH) transcription factor, controls the fate of intestinal stem cells. However, the role of Ascl2 in colon cancer progenitor cells remains unknown. The cell line HT-29 (47.5–95% of CD133+ population) and LS174T (0.45% of CD133+ population) were chosen for functional evaluation of Ascl2 in colon cancer progenitor cells after gene knockdown by RNA interference. Methodology/Principal Findings: Immunohistochemistry demonstrated that Ascl2 was significantly increased in colorectal adenocarcinomas. Downregulation of Ascl2 using RNA interference in cultured colonic adenocarcinoma HT-29 and LS174T cells reduced cellular proliferation, colony-forming ability, invasion and migration in vitro, and resulted in the growth arrest of tumor xenografts in vivo. The Ascl2 protein level in CD133+ HT-29 cells was significantly higher than in CD1332 HT-29 cells. Ascl2 blockade via shRNA interference in HT-29 cells (shRNA-Ascl2/H