title: MicroRNA-135b regulates apoptosis and chemoresistance in colorectal cancer by targeting large tumor suppressor kinase 2.
abstract: Colorectal cancer remains the third most common cause of death from cancer worldwide. MicroRNA emerges as a good area of research for current cancer therapy. Here, we identified miR-135b to be a contributor to anti-apoptosis and chemoresistance in colorectal cancer. We observed high levels of miR-135b in colorectal cancer cell lines and clinical tissues, compared to colorectal epithelium cell line and noncancerous tissues. Furthermore, enforced expression of miR-135b attenuated doxorubicin-induced apoptosis in colorectal cells. (Doxorubicin alone can trigger significant apoptosis). In elucidating the molecular mechanism by which miR-135b participate in the regulation of apoptosis and chemoresistance in colorectal cancer, we discovered that large tumor suppressor kinase 2 (LATS2) is a direct target of miR-135b. The role of miR-135b was confirmed in colorectal tumor xenograft models. The growth of established tumors was suppressed by an inhibition of miR-135b expression and enhanced apoptosis was further assessed by TUNEL assay. Taken together, our results reveal that miR-135b and LATS2 axis may be a novel therapeutic target for colorectal cancer.
authors.affiliation: Department of Gastroenterology, Beijing Military General Hospital Beijing 100700, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: He
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University Qingdao 266021, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Beijing Military General Hospital Beijing 100700, China.
authors.forename: Jiheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology & Hepatology, University of California Davis, UC Davis Medical Center Sacramento, CA 95817.
authors.forename: Victoria Yee-Wa
authors.initials: VY
authors.lastname: Yung
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles Los Angeles, CA 90095.
authors.forename: Emily
authors.initials: E
authors.lastname: Hsu
authors.affiliation: Department of Gastroenterology, Beijing Military General Hospital Beijing 100700, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Beijing Military General Hospital Beijing 100700, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Kang
authors.affiliation: Department of Coloproctology, The People's Hospital of Renqiu City Renqiu 062550, China.
authors.forename: Junbiao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Coloproctology, The People's Hospital of Renqiu City Renqiu 062550, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, Beijing Military General Hospital Beijing 100700, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute Beijing, 100142, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute Beijing, 100142, China.
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Beijing Military General Hospital Beijing 100700, China.
authors.forename: Jianqiu
authors.initials: J
authors.lastname: Sheng
keywords: LATS2; chemoresistance; colorectal cancer; miR-135b