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Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma
Authors:Haoran Peng  Masaharu Ishida  Ling Li  Atsushi Saito  Atsushi Kamiya  James P. Hamilton  Rongdang Fu  Alexandru V. Olaru  Fangmei An  Irinel Popescu  Razvan Iacob  Simona Dima  Sorin T. Alexandrescu  Razvan Grigorie  Anca Nastase  Ioana Berindan-Neagoe  Ciprian Tomuleasa  Florin Graur  Florin Zaharia  Michael S. Torbenson  Esteban Mezey  Minqiang Lu  Florin M. Selaru
Abstract:The complex regulation of tumor suppressive gene and its pseudogenes play key roles in the pathogenesis of hepatocellular cancer (HCC). However, the roles played by pseudogenes in the pathogenesis of HCC are still incompletely elucidated. This study identifies the putative tumor suppressor INTS6 and its pseudogene INTS6P1 in HCC through the whole genome microarray expression. Furthermore, the functional studies – include growth curves, cell death, migration assays and in vivo studies – verify the tumor suppressive roles of INTS6 and INTS6P1 in HCC. Finally, the mechanistic experiments indicate that INTS6 and INTS6P1 are reciprocally regulated through competition for oncomiR-17-5p. Taken together, these findings demonstrate INTS6P1 and INTS6 exert the tumor suppressive roles through competing for oncomiR-17-5p. Our investigation of this regulatory circuit reveals novel insights into the underlying mechanisms of hepatocarcinogenesis.
Keywords:hepatocellular carcinoma   pseudogene   tumor suppressor   competitive endogenous RNA   INTS6
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