Int J Biol Sci 2022; 18(1):140-153. doi:10.7150/ijbs.65676 This issue

Research Paper

SLPI suppresses hepatocellular carcinoma progression via endoplasmic reticulum stress induced apoptosis

Jie Sun1*, Jinfan Li1*, Zhen Wu5, Yuwan Liang5, Rong Duan1, Mengsha Zheng1, Jing Wang4✉, Derun Kong2,3✉

1. Department of Pathology, Second Affiliated Hospital of Zhejiang University School of medicine, Jiefang Road 88, Hangzhou 310009, Zhejiang Province, China.
2. Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230032, China.
3. Department of Gastroenterology, Fuyang Hospital of Anhui Medical University, Huangshan Road 99, Fuyang, 236000, China.
4. Department of Ultrasound in Medicine, Second Affiliated Hospital of Zhejiang University School of medicine, Jiefang Road 88, Hangzhou 310009, Zhejiang Province, China.
5. Department of Hygiene Inspection and Quarantine, School of Public Health, Anhui Medical University, Meishan Road 81, Hefei 230022, Anhui Province, China.
*These authors contributed equally to this work.

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Citation:
Sun J, Li J, Wu Z, Liang Y, Duan R, Zheng M, Wang J, Kong D. SLPI suppresses hepatocellular carcinoma progression via endoplasmic reticulum stress induced apoptosis. Int J Biol Sci 2022; 18(1):140-153. doi:10.7150/ijbs.65676. Available from https://www.ijbs.com/v18p0140.htm

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Abstract

Graphic abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Secretory leukocyte protease inhibitor (SLPI) has been reported to function as a regulatory factor in several cancers. However, its biological functions and underlying mechanisms in HCC remain to be uncovered. Here, we aimed to explore the effect of SLPI in HCC. In our study, we found that the mRNA and protein expression levels of SLPI were significantly down-regulated in HCC tissues and hepatoma cell lines and low level of SLPI predicted worse survival in our HCC cohorts. In term of function, silencing of SLPI markedly promoted whereas overexpression SLPI suppressed proliferation, migration and invasion capabilities of HCC cells in vitro, and ectopic expression of SLPI inhibited the tumorigenicity of HCC cells in vivo. Mechanistic studies demonstrated that SLPI played a protective role in HCC progression via activating endoplasmic reticulum stress (ER stress)-mediated apoptosis of hepatoma cells, which could be regulated by MAPK signaling pathways. In summary, our findings highlight that SLPI could serve as a potential prognostic biomarker and putative tumor suppressor by enhancing ER stress-induced apoptosis in HCC cells mediated by MAPK signaling pathways, which provides new insights into promising therapeutic targets for HCC treatment.

Keywords: SLPI, Secretory leukocyte protease inhibitor, Hepatocellular carcinoma, Endoplasmic reticulum stress, Apoptosis, MAPK.