J Cancer 2021; 12(1):89-98. doi:10.7150/jca.47526

Research Paper

Inhibition of SPATS2 Suppresses Proliferation and Invasion of Hepatocellular Carcinoma Cells through TRIM44-STAT3 Signaling Pathway

Lirong Chen1*, Chenhe Yi2*, Wenshuai Li1*, Yujen Tseng1, Jun Zhang1✉, Jie Liu1✉

1. Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, PR China.
2. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, PR China.
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Chen L, Yi C, Li W, Tseng Y, Zhang J, Liu J. Inhibition of SPATS2 Suppresses Proliferation and Invasion of Hepatocellular Carcinoma Cells through TRIM44-STAT3 Signaling Pathway. J Cancer 2021; 12(1):89-98. doi:10.7150/jca.47526. Available from https://www.jcancer.org/v12p0089.htm

File import instruction

Abstract

Hepatocellular carcinoma (HCC) is a major global health burden and its treatment options are limited. Spermatogenesis associated serine rich 2(SPATS2), a recent defined oncogene, was found to be a prognostic biomarker in HCC. However, the explicit mechanism underlying SPATS2 was urged to be elucidated. In vitro, knockdown of SPATS2 hampered the proliferation, invasion and migration of HCC cells. Moreover, phosphorylation of signal transducer and activator of transcription 3 (STAT3) and its downstream oncogenes were dramatically suppressed by SPATS2 knockdown. In addition, tripartite motif containing 44 (TRIM44) was found to be positively associated with SPATS2 in TCGA and declined after SPATS2 knockdown in HCC cells. Overexpression of TRIM44 rescued the effect of SPATS2 silencing on p-STAT3 and its downstream oncogenes. In vivo, SPATS2 silencing was confirmed to impede HCC tumor development in nude mice. In our own cohort containing 112 HCC patients, high SPATS2 protein level is indicative of an unfavorable clinicopathological feature and poor prognosis and could serve as an independent risk factor. Collectively, the present study is the first to propose the mechanism of significance of SPATS2-TRIM44-p-STAT3 in HCC and provide a new theoretical basis for targeted therapy.

Keywords: SPATS2, TRIM44, STAT3, Hepatocellular carcinoma