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IL- 17A inhibits autophagic activity of HCC cells by inhibiting the degradation of Bcl2

Author:
Li, Sheng, Lin, Zhenwen, Zheng, Wang, Zheng, Lisheng, Chen, Xi, Yan, Zixing, Cheng, Zhuqin, Yan, Haiyi, Zheng, Cui, Guo, Peng
Source:
Biochemical and biophysical research communications 2019 v.509 no.1 pp. 194-200
ISSN:
0006-291X
Subject:
autophagy, dissociation, hepatoma, interleukin-17, prognosis, protective effect, starvation, viability
Abstract:
Hepatocellular carcinoma (HCC) is associated with poor prognosis due to many unknowns about its inflammatory microenvironment. As a pivotal proinflammatory cytokine, IL-17A exerts a protective effect on the survival and function of HCC cells. It is widely accepted that IL-17A plays an important role in regulating autophagy. Bcl2, a key molecule promoting the survival of HCC cells, also plays an indispensable role as an autophagy regulator. The aim of this study was to investigate the role of Bcl2 in IL-17A-regulated autophagy of HCC cells. The results showed that IL-17A not only inhibited autophagic activity, but also increased Bcl2 levels in HCC cells under starvation. Besides, IL-17A could prevent the dissociation of autophagy protein Beclin1 from Bcl2-Beclin1 complex upon starvation. Overexpression of Beclin1 rescued the autophagy deficiency of HCC cells in presence of IL-17A. Moreover, RNAi-induced Bcl2 silencing impaired the function of IL-17A in inhibiting the activation of autophagy, subsequently reducing the viability and migration of HCC cells, while the inhibition of Beclin1 by spautin-1 could reduce autophagic activity to a certain degree, thus restoring the viability and migration of HCC cells. In summary, it was suggested that the inhibition of Bcl2 degradation may be an important mechanism by which IL-17A inhibits autophagy response, subsequently maintaining the survival in HCC cells.
Agid:
6263952