Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells

// Zhi-Yan Hu 1, 2, 3, * , Xiao-Yan Wang 1, 2, 3, * , Wen-bin Guo 4, 5, 6, * , Lin-Ying Xie 1, 2, 3 , Yu-qi Huang 4 , Yan-Ping Liu 1, 2, 3 , Li-Wei Xiao 1, 2, 3 , Sheng-Nan Li 1, 2, 3 , Hui-Fang Zhu 1, 2, 3 , Zu-Guo Li 1, 2, 3 , Heping Kan 4 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China 3 Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Southern Medical University, Guangzhou, China 4 Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China 5 Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 6 Department of Urology, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, China * These authors contributed equally to this work Correspondence to: Heping Kan, e-mail: khp5513@126.com Zu-Guo Li, e-mail: Lizg@smu.edu.cn Keywords: long non-coding RNA, MALAT-1, AKAP-9, SRSF1, colorectal cancer Received: September 24, 2015      Accepted: January 23, 2016      Published: February 13, 2016 ABSTRACT Our earlier findings indicate that the long non-coding RNA MALAT1 promotes colorectal cancer (CRC) cell proliferation, invasion and metastasis in vitro and in vivo by increasing expression of AKAP-9. In the present study, we investigated the molecular mechanism by which MALAT1 enhances AKAP9 expression in CRC SW480 cells. We found that MALAT1 interacts with both SRPK1 and SRSF1. MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation. Following MALAT1 knockdown, overexpression of SRPK1 was sufficient to restore SRSF1 phosphorylation and AKAP-9 expression to a level that promoted cell proliferation, invasion and migration in vitro . Conversely, SRPK1 knockdown after overexpression of MALAT1 in SW480 cells diminished SRSF1 phosphorylation and AKAP-9 expression and suppressed cell proliferation, invasion and migration in vitro . These findings suggest MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in CRC cells. These results reveal a novel molecular mechanism by which MALAT1 regulates AKAP-9 expression in CRC cells.