SREBP-1 has a prognostic role and contributes to invasion and metastasis in human hepatocellular carcinoma.

Chao Li,Yingmin Yao,Wei Yang,Qingguang Liu,Kangsheng Tu,Junli Zhang,Xin Zheng

doi:10.3390/ijms15057124

Abstract

Sterol regulatory element-binding protein 1 (SREBP-1) is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC), is still unclear. In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor-adjacent tissues (p < 0.05). SREBP-1 was expressed at significantly higher levels in patients with large tumor size, high histological grade and advanced tumor-node-metastasis (TNM) stage (p < 0.05). The positive expression of SREBP-1 correlated with a worse 3-year overall and disease-free survival of HCC patients (p < 0.05). Additionally, SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p < 0.05). In vitro studies revealed that downregulation of SREBP-1 inhibited cell proliferation and induced apoptosis in both HepG2 and MHCC97L cells (p < 0.05). Furthermore, wound healing and transwell assays showed that SREBP-1 knockdown prominently inhibited cell migration and invasion in both HepG2 and MHCC97L cells (p < 0.05). These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell growth and metastasis.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with about750,000 patients newly diagnosed each year [1]
Values are depicted as mean ± SD; (B) and (D) Quantification of apoptotic cell population by flow cytometry; Sterol regulatory element-binding protein 1 (SREBP-1) knockdown in (B) HepG2 and (D) MHCC97L cells exhibited a larger subset of apoptotic cells compared with control cells. n = 3
We demonstrated that sterol regulatory element binding proteins (SREBPs)-1 was significantly upregulated in HCC tissues compared with normal tumor-adjacent tissues, and elevated SREBP-1 expression was significantly associated with large tumor size (>5 cm), high Edmonson-Steiner classification and advanced TNM stage

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with about750,000 patients newly diagnosed each year [1]. Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with about. HCC is a global health problem [2]. In Asian countries, especially China, hepatitis B and C virus infection are the main risk factors for HCC development [3]. Various treatments including hepatectomy and liver transplantation are applied in clinical practice, the prognosis for HCC patients is still not ideal. Recent studies showed that nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is associated with an increased risk of HCC [4]. These reports suggest that abnormal lipid metabolism may play an essential role in the oncogenesis of HCC. The sterol regulatory element binding proteins (SREBPs) were originally identified in nuclear extracts in Hela cells

Results

Discussion

Conclusion