title: miR-20a-directed regulation of BID is associated with the TRAIL sensitivity in colorectal cancer.
abstract: MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in cancer processes. Although miR-20a has been reported to be altered in a range of cancers, the role of miR-20a in colorectal cancer is not fully characterized, and the relationship between miR-20a dysregulation and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity is not defined. In the present study, we demonstrated significant upregulation of miR-20a in the serum of colorectal cancer patients, tumor tissues and cell lines by quantitative RT-PCR analysis. Furthermore, we found that the TRAIL-induced apoptosis was associated with the expression level of miR-20a in colorectal cancer. The knockdown of miR-20a by inhibitors increased the antitumor effect of TRAIL via caspase-8 dependent pathway. BID, which is a pro-apoptotic member of the Bcl-2 family, was found to be directly regulated by miR-20a in SW480 cells. The knockdown of miR-20a inhibited the translocation of tBID to the mitochondria, which induced the mitochondrial pathway of apoptosis. Notably, we found that the knockdown of miR-20a also reversed the resistance of TRAIL in established TRAIL-resistant SW480 cells by tBID-mitochondria pathway. Therefore, our results suggest that miR-20a acts as a tumor promoter in colorectal cancer, and the understanding of the miR-20a might be a potential therapeutic target for colorectal cancer.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors.forename: Guanli
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Yefeng
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors.forename: Chungen
authors.initials: C
authors.lastname: Xing
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D053221:TNF-Related Apoptosis-Inducing Ligand