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

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

doi:10.1186/s12935-021-02421-w

Abstract

BackgroundSerine/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.MethodsImmunohistochemistry 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.ResultsSTK25 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.ConclusionsOur 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.

Highlights

Serine/threonine protein kinase 25 (STK25) plays an important role in regulating glucose and insulin homeostasis and in ectopic lipid accumulation
To confirm the difference in STK25 expression in the hepatocellular carcinoma (HCC) tissues, we examined the tumor specimens and paracancerous tissues of 29 patients
The correlation between key genes of lipid metabolism and prognosis of HCC patients was predicted by GEPIA, we found that ACC1 and ATP citrate lyase (ACLY) are related to the prognosis of patients (Fig. 4b, c)

Summary

Introduction

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). The mortality rate of liver cancer increased by 4.6% from 2005 to 2015 [1]. Hepatocellular carcinoma (HCC) accounts for more than 80% of primary liver cancers. Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in most developed countries and has become the main risk factor for HCC [3, 4]. The mechanisms of how NAFLD develops into HCC remain unclear. It is of great clinical significance to explore how the liver transforms from benign steatosis to liver cancer and achieve early interventions

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