HLTF promotes hepatocellular carcinoma progression by enhancing SRSF1 stability and activating ERK/MAPK pathway

Yanan Xu; Shanjia Ke; Shounan Lu; Chaoqun Wang; Zihao Li; Zhigang Feng; Hongjun Yu; Miaoyu Bai; Baolin Qian; Bing Yin; Xinglong Li; Yongliang Hua; Hongchi Jiang; Yong Ma

doi:10.1038/s41389-023-00447-5

HLTF promotes hepatocellular carcinoma progression by enhancing SRSF1 stability and activating ERK/MAPK pathway

Oncogenesis. 2023 Jan 20;12(1):2. doi: 10.1038/s41389-023-00447-5.

Authors

Yanan Xu^#^{1

2}, Shanjia Ke^#^{1

2}, Shounan Lu^#^{1

2}, Chaoqun Wang^{1

2}, Zihao Li^{1

2}, Zhigang Feng^{1

2

3}, Hongjun Yu^{1

2}, Miaoyu Bai^{1

2}, Baolin Qian^{1

2}, Bing Yin^{1

2}, Xinglong Li^{1

2}, Yongliang Hua^{1

4}, Hongchi Jiang^{5

6}, Yong Ma^{7

8}

Affiliations

¹ Key Laboratory of Hepatosplenic Surgery, Ministry of Education, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Department of Minimal Invasive Hepatic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
³ The First Department of General Surgery, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, China.
⁴ Department of Pediatric Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁵ Key Laboratory of Hepatosplenic Surgery, Ministry of Education, the First Affiliated Hospital of Harbin Medical University, Harbin, China. jianghc2013@163.com.
⁶ Department of Minimal Invasive Hepatic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China. jianghc2013@163.com.
⁷ Key Laboratory of Hepatosplenic Surgery, Ministry of Education, the First Affiliated Hospital of Harbin Medical University, Harbin, China. mayong@ems.hrbmu.edu.cn.
⁸ Department of Minimal Invasive Hepatic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China. mayong@ems.hrbmu.edu.cn.

^# Contributed equally.

Abstract

Helicase-like transcription factor (HLTF) has been found to be involved in the progression of several tumors, but the role of HLTF in hepatocellular carcinoma (HCC) progression has not been studied. Here, our study explored the underlying mechanism of HLTF in HCC progression for the first time. Database analysis and clinical sample examination indicated that HLTF was upregulated in HCC tissues and was related to poor clinicopathological features in patients. Upregulation of HLTF accelerated the growth and metastasis of HCC cells both in vitro and in vivo. Bioinformatics analysis and subsequent experiments revealed that ERK/MAPK signaling pathway activation was vital to HLTF-mediated proliferation and metastasis in HCC cells. Moreover, HLTF was demonstrated to interact with SRSF1 and contribute to its protein stability to activate the ERK/MAPK signaling pathway and enhance HCC growth and metastasis. In addition, miR-511-5p was expressed at a low level in HCC tissues, was negatively correlated HLTF, and regulated HLTF expression. Our study shows that HLTF plays an oncogenic role in HCC progression and provides a novel biomarker and therapeutic target for the diagnosis and treatment of HCC.