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KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be i...

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Autores principales: Liu, Zhao-chen, Li, Lu-Hao, Li, Ding-Yang, Gao, Zhi-Qiang, Chen, Dong, Song, Bin, Jiang, Bing-Hua, Dang, Xiao-wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732450/
https://www.ncbi.nlm.nih.gov/pubmed/36505780
http://dx.doi.org/10.3389/fonc.2022.1060574
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author Liu, Zhao-chen
Li, Lu-Hao
Li, Ding-Yang
Gao, Zhi-Qiang
Chen, Dong
Song, Bin
Jiang, Bing-Hua
Dang, Xiao-wei
author_facet Liu, Zhao-chen
Li, Lu-Hao
Li, Ding-Yang
Gao, Zhi-Qiang
Chen, Dong
Song, Bin
Jiang, Bing-Hua
Dang, Xiao-wei
author_sort Liu, Zhao-chen
collection PubMed
description Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be implicated in the pathogenesis of multiple cancers. However, how KIAA1429 functions in alternative splicing is not fully reported. In the current study, multi-omics sequencing data were used to analyze and decipher the molecular functions and the underlying mechanisms of KIAA1429 in HCC samples. RNA sequencing data (RNA-seq) analysis demonstrated that in HCCLM3 cells, alternative splicing (AS) profiles were mediated by KIAA1429. Regulated AS genes (RASGs) by KIAA1429 were enriched in cell cycle and apoptosis-associated pathways. Furthermore, by integrating the RNA immunoprecipitation and sequencing data (RIP-seq) of KIAA1429, we found that KIAA1429-bound transcripts were highly overlapping with RASGs, indicating that KIAA1429 could globally regulate the alternative splicing perhaps by binding to their transcripts in HCCLM3 cells. The overlapping RASGs were also clustered in cell cycle and apoptosis-associated pathways. In particular, we validated the regulated AS events of three genes using clinical specimens from HCC patients, including the exon 6 of BPTF gene and a marker gene of HCC. In summary, our results shed light on the regulatory functions of KIAA1429 in the splicing process of pre-mRNA and provide theoretical basis for the targeted therapy of HCC.
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spelling pubmed-97324502022-12-10 KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma Liu, Zhao-chen Li, Lu-Hao Li, Ding-Yang Gao, Zhi-Qiang Chen, Dong Song, Bin Jiang, Bing-Hua Dang, Xiao-wei Front Oncol Oncology Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be implicated in the pathogenesis of multiple cancers. However, how KIAA1429 functions in alternative splicing is not fully reported. In the current study, multi-omics sequencing data were used to analyze and decipher the molecular functions and the underlying mechanisms of KIAA1429 in HCC samples. RNA sequencing data (RNA-seq) analysis demonstrated that in HCCLM3 cells, alternative splicing (AS) profiles were mediated by KIAA1429. Regulated AS genes (RASGs) by KIAA1429 were enriched in cell cycle and apoptosis-associated pathways. Furthermore, by integrating the RNA immunoprecipitation and sequencing data (RIP-seq) of KIAA1429, we found that KIAA1429-bound transcripts were highly overlapping with RASGs, indicating that KIAA1429 could globally regulate the alternative splicing perhaps by binding to their transcripts in HCCLM3 cells. The overlapping RASGs were also clustered in cell cycle and apoptosis-associated pathways. In particular, we validated the regulated AS events of three genes using clinical specimens from HCC patients, including the exon 6 of BPTF gene and a marker gene of HCC. In summary, our results shed light on the regulatory functions of KIAA1429 in the splicing process of pre-mRNA and provide theoretical basis for the targeted therapy of HCC. Frontiers Media S.A. 2022-11-25 /pmc/articles/PMC9732450/ /pubmed/36505780 http://dx.doi.org/10.3389/fonc.2022.1060574 Text en Copyright © 2022 Liu, Li, Li, Gao, Chen, Song, Jiang and Dang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Liu, Zhao-chen
Li, Lu-Hao
Li, Ding-Yang
Gao, Zhi-Qiang
Chen, Dong
Song, Bin
Jiang, Bing-Hua
Dang, Xiao-wei
KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma
title KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma
title_full KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma
title_fullStr KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma
title_full_unstemmed KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma
title_short KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma
title_sort kiaa1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732450/
https://www.ncbi.nlm.nih.gov/pubmed/36505780
http://dx.doi.org/10.3389/fonc.2022.1060574
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