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Oncotarget. 2017 Feb 21;8(8):13690-13702. doi: 10.18632/oncotarget.14625.

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.

Li Y1,2,3, Li Y1,2, Huang S1,2, He K4, Zhao M1,2, Lin H1,2, Li D1,2, Qian J4, Zhou C5, Chen Y3, Huang C1,2.

Author information

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.

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.

KEYWORDS:

GAS5; VEGF; colorectal cancer; interleukin-10; long non-coding RNA

PMID:
28099146
PMCID:
PMC5355130
DOI:
10.18632/oncotarget.14625
[Indexed for MEDLINE]
Free PMC Article

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