RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy
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Hui Wang1,*, Yanan Wang1,*, Liu Qian1,*, Xue Wang1, Hailiang Gu2, Xiaoqiang Dong2, Shiqian Huang1, Min Jin1, Hailiang Ge1, Congfeng Xu1, Yanyun Zhang1
1Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China
2Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
*These authors have contributed equally to this work
Yanyun Zhang, email: [email protected]
Congfeng Xu, email: [email protected]
Hailiang Ge, email: [email protected]
Keywords: RNF216, BECN1, autophagy, colorectal cancer
Received: January 29, 2016 Accepted: April 28, 2016 Published: May 18, 2016
Originally identified as an E3 ligase regulating toll-like receptor (TLR) signaling, ring finger protein 216 (RNF216) also plays an essential role in autophagy, which is fundamental to cellular homeostasis. Autophagy dysfunction leads to an array of pathological events, including tumor formation. In this study, we found that RNF216 was upregulated in human colorectal cancer (CRC) tissues and cell lines, and was associated with progression of CRC. RNF216 promoted CRC cell proliferation and migration in vitro and in vivo, largely by enhancing proteasomal degradation of BECN1, a key autophagy regulator and tumor suppressor. RNF216 restricted CRC cell autophagy through BECN1 inhibition under nutritional starvation conditions. RNF216 knockdown increased the autophagy, limiting CRC cell proliferation and migration. Moreover, BECN1 knockdown or autophagy inhibition restored proliferation and migration of RNF216-knockdown CRC cells. Collectively, our results suggested that RNF216 promoted CRC cell proliferation and migration by negatively regulating BECN1-dependent autophagy. This makes RNF216 as a potential biomarker and novel therapeutic target for inhibiting CRC development and progression.
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