Long non-coding RNA growth arrest specific transcript 5 acts as a tumour suppressor in colorectal cancer by inhibiting interleukin-10 and vascular endothelial growth factor expression

// Yuan Li 1, 2, 3 , Yan Li 1, 2 , Shengkai Huang 1, 2 , Kun He 4 , Mei Zhao 1, 2 , Hong Lin 1, 2 , Dongdong Li 1, 2 , Jiaming Qian 4 , Caihong Zhou 5 , Yuhua Chen 3 , Changzhi Huang 1, 2 1 State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China 2 Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China 3 Department of Developmental Biology, China Medical University, Shenyang, 110122, China 4 Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China 5 Department of Education, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China Correspondence to: Changzhi Huang, email: huangpumc@163.com Yuhua Chen, email: yhchen@mail.cmu.edu.cn Jiaming Qian, email: qianjiaming1957@126.com Caihong Zhou, email: caihongzhou2006@126.com Keywords: colorectal cancer, long non-coding RNA, GAS5, interleukin-10, VEGF Received: July 16, 2016 Accepted: January 06, 2017 Published: January 13, 2017 ABSTRACT Long non-coding RNAs (lncRNAs) are highly involved in diverse biological processes of human malignancies. The expression profile and underlying mechanism of lncRNA growth arrest specific transcript 5 (GAS5) in colorectal cancer (CRC) is poorly understood. In this study, we found that GAS5 was commonly downregulated in CRC tissues, serum of CRC patients and CRC cell lines. Knockdown of GAS5 promoted CRC cell proliferation and colony formation, whereas overexpression of GAS5 produced the opposite result. We further demonstrated that knockdown of GAS5 increased the expression and secretion of interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF-A) via NF-κB and Erk1/2 pathways. Neutralization of IL-10 and VEGF-A reduced tumour proliferation caused by GAS5 knockdown. Moreover, GAS5 expression showed a statistically significant correlation with the mRNA levels of IL-10 and VEGF-A in CRC tissues. We further illustrated that GAS5 was markedly downregulated and negatively correlated with the cytokine expression in a mouse model of colitis-associated cancer (CAC). These results delineate a novel mechanism of lncRNA GAS5 in suppressing colorectal carcinogenesis. The cytokines IL-10 and VEGF-A inhibited by GAS5 may provide targets for lncRNA-based therapies for CRC.