circ_HMGCS1 modulates hepatocellular carcinoma chemoresistance via miR‐338‐5p/IL‐7 pathway

Author:

Zhang Siyu12,Ma Jun1,Yu Tingdong1,Song Zhengrui1,Lau Wan Yee3,Zha Yong1ORCID

Affiliation:

1. Department of Hepatobiliary and Pancreatic Surgery The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital Kunming China

2. Department of Medical Oncology Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center Affiliated Cancer Hospital of University of Electronic Science and Technology of China Chengdu China

3. Faculty of Medicine The Chinese University of Hong Kong Hong Kong SAR China

Abstract

AbstractHepatocellular cancer is one of the most serious types of cancer in the world, with high incidence and mortality rates. Most HCC patients with long‐term chemotherapy develop chemoresistance, leading to a poor prognosis. However, the underlying mechanism of circRNAs in HCC chemoresistance remains unclear. Our research found that circ_0072391(circ_HMGCS1) expression was significantly upregulated in cisplatin‐resistant HCC cells. The silence of circ_HMGCS1 attenuated the cisplatin resistance in HCC. Results showed that circ_HMGCS1 regulated the expression of miR‐338‐5p via acting as microRNA sponges. Further study confirmed that miR‐338‐5p regulated the expression of IL‐7. IL‐7 could remodel the immune system by improving T‐cell function and antagonising the immunosuppressive network. IL‐7 is an ideal target used to enhance the function of the immune system. circ_HMGCS1 exerts its oncogenic function through the miR‐338‐5p/IL‐7 pathway. Inhibition of circ_HMGCS1/miR‐338‐5p/IL‐7 could effectively attenuate the chemoresistance of HCC. IL‐7 might be a promising immunotherapy target for HCC cancer treatment.

Publisher

Wiley

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