Long noncoding RNA HClnc1 promotes proliferation and migration of liver cancer cells by targeting RBBP5/KAT2B complex to enhance ODC1 transcription.
10.12122/j.issn.1673-4254.2025.09.11
- Author:
Zhihui FENG
1
;
Wenyue LI
2
;
Mingxiu ZHANG
1
;
Peipei WANG
3
;
Yangyang SHUAI
3
;
Hong ZHANG
1
Author Information
1. College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
2. Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
3. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
- Publication Type:Journal Article
- Keywords:
HClnc1;
KAT2B;
ODC1;
RBBP5;
hepatocellular carcinoma;
long noncoding RNA
- MeSH:
Humans;
Cell Proliferation;
RNA, Long Noncoding/genetics*;
Cell Movement;
Liver Neoplasms/metabolism*;
Cell Line, Tumor;
Carcinoma, Hepatocellular/genetics*;
Promoter Regions, Genetic;
Gene Expression Regulation, Neoplastic
- From:
Journal of Southern Medical University
2025;45(9):1919-1926
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the role of long noncoding RNA (lncRNA) HClnc1 in regulating proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells and the regulatory mechanism.
METHODS:HClnc1 expression levels in liver cancer tissues were analyzed using data from the TCGA database. BrdU incorporation, plate cloning, and transwell assays were employed to examine the effects of HClnc1 silencing/overexpression and/or ODC1 silencing on proliferation, invasion, and migration of liver cancer cells. The effects of HClnc1 silencing on ODC1 protein and mRNA expression in the liver cancer cells were analyzed using qRT-PCR and Western blotting. The activity of ODC1 promoter was analyzed using a dual luciferase reporter gene assay. Pull-down experiment, mass spectrometry analysis, and chromatin immunoprecipitation (ChIP) assay were used for identification of HClnc1-binding proteins and their interactions. Protein interactions with the ODC1 promoter region and their binding efficiencies were investigated using RNA interference and ChIP analysis.
RESULTS:HClnc1 was significantly overexpressed in HCC tissues. In liver cancer cells, HClnc1 silencing significantly inhibited cell proliferation, invasion, and migration, while HClnc1 overexpression promoted these behaviors. ODC1 silencing also suppressed malignant behaviors of liver cancer cells, and counteracted the effects of HClnc1 overexpression. Interference of HClnc1 obviously inhibited ODC1 promoter activity. RBBP5 and KAT2B proteins were identified to bind simultaneously with HClnc1. HClnc1 overexpression upregulated ODC1 protein expression, while interference of RBBP5 or KAT2B downregulated ODC1 protein expression and blocked HClnc1-induced upregulation of ODC1 protein. Both RBBP5 and KAT2B could directly bind to ODC1 promoter region; knocking out KAT2B or RBBP5 reduced the binding efficiency, while knocking out HClnc1 reduced the binding of both RBBP5 and KAT2B to ODC1 promoter region.
CONCLUSIONS:By targeting the RBBP5/KAT2B epigenetic modification complex, HClnc1 increases ODC1 promoter activity to enhance ODC1 transcription and promote the proliferation and migration of liver cancer cells.
