Research Papers:
Long noncoding RNA growth arrest specific transcript 5 acts as a tumour suppressor in colorectal cancer by inhibiting interleukin10 and vascular endothelial growth factor expression
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Yuan Li1,2,3, Yan Li1,2, Shengkai Huang1,2, Kun He4, Mei Zhao1,2, Hong Lin1,2, Dongdong Li1,2, Jiaming Qian4, Caihong Zhou5, Yuhua Chen3, Changzhi Huang1,2
1State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China
2Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China
3Department of Developmental Biology, China Medical University, Shenyang, 110122, China
4Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
5Department 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: [email protected]
Yuhua Chen, email: [email protected]
Jiaming Qian, email: [email protected]
Caihong Zhou, email: [email protected]
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.