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

被引:10
|
作者
Xu, Yanan [1 ,2 ]
Ke, Shanjia [1 ,2 ]
Lu, Shounan [1 ,2 ]
Wang, Chaoqun [1 ,2 ]
Li, Zihao [1 ,2 ]
Feng, Zhigang [1 ,2 ,3 ]
Yu, Hongjun [1 ,2 ]
Bai, Miaoyu [1 ,2 ]
Qian, Baolin [1 ,2 ]
Yin, Bing [1 ,2 ]
Li, Xinglong [1 ,2 ]
Hua, Yongliang [1 ,4 ]
Jiang, Hongchi [1 ,2 ]
Ma, Yong [1 ,2 ]
机构
[1] Harbin Med Univ, Key Lab Hepatosplen Surg, Minist Educ, Affiliated Hosp 1, Harbin, Peoples R China
[2] Harbin Med Univ, Dept Minimal Invas Hepat Surg, Affiliated Hosp 1, Harbin, Peoples R China
[3] Inner Mongolia Minzu Univ, Dept Gen Surg 1, Affiliated Hosp, Tongliao, Peoples R China
[4] Harbin Med Univ, Dept Pediat Surg, Affiliated Hosp 1, Harbin, Peoples R China
基金
中国博士后科学基金; 黑龙江省自然科学基金;
关键词
TRANSCRIPTION FACTOR; GENE-EXPRESSION; CANCER; METHYLATION; SF2/ASF;
D O I
10.1038/s41389-023-00447-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:11
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