Research Papers:
Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells
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Abstract
Zhi-Yan Hu1,2,3,*, Xiao-Yan Wang1,2,3,*, Wen-bin Guo4,5,6,*, Lin-Ying Xie1,2,3, Yu-qi Huang4, Yan-Ping Liu1,2,3, Li-Wei Xiao1,2,3, Sheng-Nan Li1,2,3, Hui-Fang Zhu1,2,3, Zu-Guo Li 1,2,3, Heping Kan4
1Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China
2Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
3Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Southern Medical University, Guangzhou, China
4Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
5Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
6Department 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: [email protected]
Zu-Guo Li, e-mail: [email protected]
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.
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