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

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 proli feration 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.

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

“…LncRNAs expressed in tumor cells may affect not only the tumor cells but also tumor-directed immune responses. For example, the tumor-suppressive growth arrest-specific transcript 5 (GAS5) lncRNA was reported to be associated with the expression of VEGF-A and IL-10 in the tumor cells (49). VEGF-A is a well-known proangiogenic molecule produced by the tumor cells.…”

Discovering novel long non-coding RNA predictors of anticancer drug sensitivity beyond protein-coding genes

“…(growth arrest-specific 5) lncRNA acts as a tumor suppressor with various proposed mechanisms of action, including, cell cycle control Mazar et al 2016;Luo et al 2017), proliferation (Kino et al 2010;Li et al 2017b) and regulation of epithelial to mesenchymal transition (EMT) program (Zhuang et al 2015). Considering the multi-faceted mechanisms by which GAS5 functions as a tumor suppressor, it is plausible that its expression may be predictive of response to multiple drugs.…”

Long non‐coding RNAs in cancer: Another layer of complexity

“…It was also demonstrated that the expression and secretion of IL‐10 and VEGF‐A were increased by knockdown of GAS5 , via NF‐κB and ERK1/2 pathways. Furthermore, neutralization of IL‐10 and VEGF‐A reduces tumor proliferation caused by GAS5 knockdown …”

“…Furthermore, neutralization of IL-10 and VEGF-A reduces tumor proliferation caused by GAS5 knockdown. 148…”