https://scholars.lib.ntu.edu.tw/handle/123456789/588082
Title: | Upregulation of microRNA-137 expression by Slug promotes tumor invasion and metastasis of non-small cell lung cancer cells through suppression of TFAP2C | Authors: | Chang, Tzu-Hua Tsai M.-F. Gow, Chien-Hung SHANG-GIN WU Liu, Yi-Nan YIH-LEONG CHANG SUNG-LIANG YU HSING-CHEN TSAI Lin, Shih-Wen Chen, Yen-Wei Kuo, Po-Yen PAN-CHYR YANG JIN-YUAN SHIH |
Keywords: | Epithelial-mesenchymal transition (EMT); Non-small cell lung cancer (NSCLC); Slug; TFAP2C; miR-137 | Issue Date: | 2017 | Journal Volume: | 402 | Source: | Cancer letters | Abstract: | The epithelial-mesenchymal transition (EMT) regulator, Slug, plays multifaceted roles in controlling lung cancer progression, but its downstream targets and mechanisms in promoting lung cancer progression have not been well defined. In particular, the miRNAs downstream of Slug in non-small cell lung cancer (NSCLC) remain undetermined. Here, we report that miR-137 is downstream of the EMT regulator, Slug, in lung cancer cells. Slug binds directly to the E-box of the miR-137 promoter and up-regulates its expression in lung cancer cells. Knockdown of miR-137 abolished Slug-induced cancer invasion and migration, whereas upregulation of miR-137 was found to trigger lung cancer cell invasion and progression by direct suppressing TFAP2C (transcription factor AP-2 gamma). Clinical data showed that lung adenocarcinoma patients with low-level expression of Slug and miR-137 but high-level expression of TFAP2C experienced significantly better survival. miR-137 is a Slug-induced miRNA that relays the pro-metastatic effects of Slug by targeting TFAP2C. Our findings add new components to the Slug-mediated regulatory network in lung cancer, and suggest that Slug, miR-137, and TFAP2C may be useful prognostic markers in lung adenocarcinoma. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/588082 | ISSN: | 03043835 | DOI: | 10.1016/j.canlet.2017.06.002 | SDG/Keyword: | messenger RNA; microRNA; microRNA 137; transcription factor AP 2; transcription factor AP 2 gamma; transcription factor Slug; unclassified drug; 3' untranslated region; antineoplastic agent; cisplatin; microRNA; MIRN137 microRNA, human; protein binding; SNAI1 protein, human; TFAP2C protein, human; transcription factor AP 2; transcription factor Snail; tumor marker; 3' untranslated region; animal experiment; animal model; animal tissue; Article; cell invasion; controlled study; down regulation; epithelial mesenchymal transition; gene expression regulation; human; human cell; human tissue; lung adenocarcinoma; lung cancer cell line; lung metastasis; mouse; non small cell lung cancer; nonhuman; overall survival; priority journal; promoter region; protein RNA binding; TFAP2C gene; tumor invasion; upregulation; adenocarcinoma; animal; binding site; cell motion; drug effects; gene expression regulation; genetic transfection; genetics; Kaplan Meier method; lung tumor; male; metabolism; mortality; non small cell lung cancer; nonobese diabetic mouse; pathology; RNA interference; SCID mouse; secondary; signal transduction; time factor; tumor cell line; tumor invasion; upregulation; 3' Untranslated Regions; Adenocarcinoma; Animals; Antineoplastic Agents; Binding Sites; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cisplatin; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Mice, Inbred NOD; Mice, SCID; MicroRNAs; Neoplasm Invasiveness; Promoter Regions, Genetic; Protein Binding; RNA Interference; Signal Transduction; Snail Family Transcription Factors; Time Factors; Transcription Factor AP-2; Transfection; Up-Regulation |
Appears in Collections: | 醫學系 |
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