Literature DB >> 27993818

Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR Activation.

Pushkar Malakar1, Asaf Shilo1, Adi Mogilevsky1, Ilan Stein2, Eli Pikarsky2, Yuval Nevo3, Hadar Benyamini3, Sharona Elgavish3, Xinying Zong4, Kannanganattu V Prasanth4, Rotem Karni5.   

Abstract

Several long noncoding RNAs (lncRNA) are abrogated in cancer but their precise contributions to oncogenesis are still emerging. Here we report that the lncRNA MALAT1 is upregulated in hepatocellular carcinoma and acts as a proto-oncogene through Wnt pathway activation and induction of the oncogenic splicing factor SRSF1. Induction of SRSF1 by MALAT1 modulates SRSF1 splicing targets, enhancing the production of antiapoptotic splicing isoforms and activating the mTOR pathway by modulating the alternative splicing of S6K1. Inhibition of SRSF1 expression or mTOR activity abolishes the oncogenic properties of MALAT1, suggesting that SRSF1 induction and mTOR activation are essential for MALAT1-induced transformation. Our results reveal a mechanism by which lncRNA MALAT1 acts as a proto-oncogene in hepatocellular carcinoma, modulating oncogenic alternative splicing through SRSF1 upregulation. Cancer Res; 77(5); 1155-67. ©2016 AACR. ©2016 American Association for Cancer Research.

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Year:  2016        PMID： 27993818      PMCID： PMC5334181          DOI： 10.1158/0008-5472.CAN-16-1508

Source DB:  PubMed          Journal:  Cancer Res        ISSN： 0008-5472            Impact factor:   12.701


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