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Open Access 01-12-2022 | Hepatocellular Carcinoma | Primary research

STK25 enhances hepatocellular carcinoma progression through the STRN/AMPK/ACC1 pathway

Authors: Yichao Zhang, Junhui Xu, Zhendong Qiu, Yongjun Guan, XiaoYi Zhang, Xin Zhang, Dongqi Chai, Chen Chen, Qinyong Hu, Weixing Wang

Published in: Cancer Cell International | Issue 1/2022

Abstract

Background

Serine/threonine protein kinase 25 (STK25) plays an important role in regulating glucose and insulin homeostasis and in ectopic lipid accumulation. It directly affects the progression and prognosis of nonalcoholic fatty liver disease (NAFLD). However, the effects of STK25 on lipid metabolism in hepatocellular carcinoma (HCC) remain unexplored. The aim of this study was to investigate the role of STK25 in HCC and to elucidate the underlying mechanisms.

Methods

Immunohistochemistry was used to measure the expression of STK25 in hepatic tissues of HCC patients, and public datasets were used as supplementary material for predicting the expression of STK25 and the prognosis of patients with HCC. The interaction between STK25 and striatin (STRN) was determined by the STRING database, immunohistochemistry and western blot analyses. The involved signaling pathway was detected by the KEGG database and western blot. Moreover, the biological behaviors of the HCC cells were detected by wound healing assays, Transwell invasion assays and oil red O staining. Finally, it was verified again by xenograft model.

Results

STK25 is highly expressed in HCC patients and is associated with poor prognosis. STK25 knockdown inhibited the HCC cell invasion and proliferation, promotes apoptosis. Consistently, STK25 knockdown inhibited tumor growth in xenograft mouse model. Besides, STK25 deficiency decreased lipid synthesis, energy reserve, epithelial-mesenchymal transition (EMT) by down-regulating lipid metabolism signaling pathway. STRN could reverse the change of lipid metabolism.

Conclusions

Our results demonstrated that STK25 interacted with STRN to regulates the energy reserve and EMT via lipid metabolism reprogramming. Accordingly, high expression of STK25 may be associated with HCC patients and poor prognosis, which implicates STK25 could be a potential target for lipid metabolism in cancer therapy.

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Title: STK25 enhances hepatocellular carcinoma progression through the STRN/AMPK/ACC1 pathway
Authors: Yichao Zhang
Junhui Xu
Zhendong Qiu
Yongjun Guan
XiaoYi Zhang
Xin Zhang
Dongqi Chai
Chen Chen
Qinyong Hu
Weixing Wang
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-021-02421-w

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