title: Induced MiR-1249 expression by aberrant activation of Hedegehog signaling pathway in hepatocellular carcinoma.
abstract: Aberrant activations of Hedegehog (Hh) signaling were found in hepatocellular carcinoma (HCC) and some other cancer types. However, the details have not been completely understood and the underlying mechanism remains unclear. Here we reported that miR-1249 transcription in HCC cells was regulated through direct binding to the conserved sequences in miR-1249 promoter region by Gli1, which functions as a transcription factor and is a component in the Hh signaling pathway. Interestingly, expression of tumor suppressor PTCH1, which is another component of the Hh signaling pathway, was inhibited by miR-1249 through targeting its 3'-untranslated region. Down-regulation of PTCH1 further enhanced the downstream effects mediated by Gli1. In consistent with these findings, miR-1249 expression level was correlated with degree of prognosis (p=0.005) in HCC patients. Taken together, our results suggested the existence of a positive feedback loop comprised of Gli1, miR-1249 and PTCH1. During the process of HCC progression, this positive feedback loop could be continuously activated to enhance tumor cell growth, migration and invasion.
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yibiao
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yunxiuxiu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yanshan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ruomei
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Guangdong General Hospital, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Pearl Laboratory Animal Sci. & Tech. Co., Ltd., Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot, PR China; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Hepatoscience Inc., Sunnyvale, CA 94085, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot, PR China.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Yu
authors.affiliation: Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot, PR China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Bai
authors.affiliation: Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot, PR China.
authors.forename: Guangpeng
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: chent_sysu@163.com.
authors.forename: Rufu
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Hepato-Pancreato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: ct0498@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D000072081:Patched-1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D035683:MicroRNAs; C000606236:PTCH1 protein, human; D000072081:Patched-1 Receptor
keywords: Hedegehog signaling pathway; Hepatocellular carcinoma; MiR-1249