NSUN2-mediated mRNA m5C Modification Regulates the Progression of Hepatocellular Carcinoma.
10.1016/j.gpb.2022.09.007
- Author:
Dan SONG
1
;
Ke AN
2
;
Wenlong ZHAI
3
;
Luyao FENG
4
;
Yingjie XU
4
;
Ran SUN
4
;
Yueqin WANG
4
;
Yun-Gui YANG
5
;
Quancheng KAN
6
;
Xin TIAN
7
Author Information
1. Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China.
2. Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China.
3. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Digestive Organ Transplantation of Henan Province, Zhengzhou University, Zhengzhou 450052, China.
4. Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China.
5. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China.
6. Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. Electronic address: kanqc@zzu.edu.cn.
7. Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. Electronic address: tianx@zzu.edu.cn.
- Publication Type:Journal Article
- Keywords:
5-methylcytosine;
Hepatocellular carcinoma;
NSUN2;
Ras pathway;
Sorafenib
- MeSH:
Humans;
ADAM Proteins;
Apoptosis Regulatory Proteins;
Carcinoma, Hepatocellular/metabolism*;
Liver Neoplasms/metabolism*;
Membrane Proteins;
Methyltransferases/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
Repressor Proteins;
RNA, Messenger/metabolism*;
Sorafenib;
RNA Methylation/genetics*
- From:
Genomics, Proteomics & Bioinformatics
2023;21(4):823-833
- CountryChina
- Language:English
-
Abstract:
RNA modifications affect many biological processes and physiological diseases. The 5-methylcytosine (m5C) modification regulates the progression of multiple tumors. However, its characteristics and functions in hepatocellular carcinoma (HCC) remain largely unknown. Here, we found that HCC tissues had a higher m5C methylation level than the adjacent normal tissues. Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways, such as the Ras and PI3K-Akt pathways. The m5C methyltransferase NSUN2 was highly expressed in HCC tissues. Interestingly, the expression of many genes was positively correlated with the expression of NSUN2, including GRB2, RNF115, AATF, ADAM15, RTN3, and HDGF. Real-time PCR assays further revealed that the expression of the mRNAs of GRB2, RNF115, and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway. Moreover, knocking down NSUN2 caused cell cycle arrest. Taken together, our study demonstrates the vital role of NSUN2 in the progression of HCC.
