Collagen 1A1 (COL1A1) is a reliable biomarker and putative therapeutic target for hepatocellular carcinogenesis and metastasis

Hon Ping Ma, Hang Lung Chang, Oluwaseun Adebayo Bamodu, Vijesh Kumar Yadav, Ting Yi Huang, Alexander T.H. Wu, Chi Tai Yeh, Shin Han Tsai, Wei Hwa Lee

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Increasing evidence shows that hepatocellular carcinoma (HCC) is a principal cause of cancer-related mortality globally, especially among Asian and African populations. Collagen type I α1 (COL1A1) is the major component of type I collagen. While aberrant expression of COL1A1 and COL1A2 is implicated in numerous cancers, the differential role of COL1A1 in malignant, premalignant and normal tissues remains unclear, and its clinical significance in HCC has not been elucidated. In this study, using bioinformatics analysis of publicly-available HCC microarray data from Gene Expression Omnibus (GEO) and RNAseq data from The Cancer Genome Atlas (TCGA) database, we determined that COL1A1 is significantly upregulated in HCC tumor tissues in comparison to normal tissues. Our analysis also revealed that COL1A1 confers survival advantage and enhanced oncogenicity on HCC cells. Interestingly, the siRNA-mediated silencing of COL1A1 expression (siCOLIA1) suppressed HCC cells clonogenicity, motility, invasiveness and tumorsphere formation. Concomitantly, siCOL1A1 abrogated Slug-dependent epithelial-to-mesenchymal transition (EMT) and HCC stemness gene-signature, by attenuating expression of stemness markers SOX2, OCT4 and CD133. The present study provides some mechanistic insight into COL1A1 activity in HCC and highlights its putative role as an important diagnostic biomarker and potential therapeutic target in early development and metastasis of HCC.

Original languageEnglish
Article number786
JournalCancers
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

Fingerprint

Hepatocellular Carcinoma
Carcinogenesis
Collagen
Biomarkers
Neoplasm Metastasis
Therapeutics
Collagen Type I
Neoplasms
Gastropoda
Epithelial-Mesenchymal Transition
Atlases
Computational Biology
Transcriptome
Small Interfering RNA
Cell Movement
Genome
Databases
Gene Expression
Mortality
Population

Keywords

  • COL1A1
  • EMT
  • Hepatocellular carcinoma
  • Metastasis
  • Stemnessk

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{eaafffa28e5945dbbc77a8646e6e346f,
title = "Collagen 1A1 (COL1A1) is a reliable biomarker and putative therapeutic target for hepatocellular carcinogenesis and metastasis",
abstract = "Increasing evidence shows that hepatocellular carcinoma (HCC) is a principal cause of cancer-related mortality globally, especially among Asian and African populations. Collagen type I α1 (COL1A1) is the major component of type I collagen. While aberrant expression of COL1A1 and COL1A2 is implicated in numerous cancers, the differential role of COL1A1 in malignant, premalignant and normal tissues remains unclear, and its clinical significance in HCC has not been elucidated. In this study, using bioinformatics analysis of publicly-available HCC microarray data from Gene Expression Omnibus (GEO) and RNAseq data from The Cancer Genome Atlas (TCGA) database, we determined that COL1A1 is significantly upregulated in HCC tumor tissues in comparison to normal tissues. Our analysis also revealed that COL1A1 confers survival advantage and enhanced oncogenicity on HCC cells. Interestingly, the siRNA-mediated silencing of COL1A1 expression (siCOLIA1) suppressed HCC cells clonogenicity, motility, invasiveness and tumorsphere formation. Concomitantly, siCOL1A1 abrogated Slug-dependent epithelial-to-mesenchymal transition (EMT) and HCC stemness gene-signature, by attenuating expression of stemness markers SOX2, OCT4 and CD133. The present study provides some mechanistic insight into COL1A1 activity in HCC and highlights its putative role as an important diagnostic biomarker and potential therapeutic target in early development and metastasis of HCC.",
keywords = "COL1A1, EMT, Hepatocellular carcinoma, Metastasis, Stemnessk",
author = "Ma, {Hon Ping} and Chang, {Hang Lung} and Bamodu, {Oluwaseun Adebayo} and Yadav, {Vijesh Kumar} and Huang, {Ting Yi} and Wu, {Alexander T.H.} and Yeh, {Chi Tai} and Tsai, {Shin Han} and Lee, {Wei Hwa}",
year = "2019",
month = "6",
day = "1",
doi = "10.3390/cancers11060786",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",

}

TY - JOUR

T1 - Collagen 1A1 (COL1A1) is a reliable biomarker and putative therapeutic target for hepatocellular carcinogenesis and metastasis

AU - Ma, Hon Ping

AU - Chang, Hang Lung

AU - Bamodu, Oluwaseun Adebayo

AU - Yadav, Vijesh Kumar

AU - Huang, Ting Yi

AU - Wu, Alexander T.H.

AU - Yeh, Chi Tai

AU - Tsai, Shin Han

AU - Lee, Wei Hwa

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Increasing evidence shows that hepatocellular carcinoma (HCC) is a principal cause of cancer-related mortality globally, especially among Asian and African populations. Collagen type I α1 (COL1A1) is the major component of type I collagen. While aberrant expression of COL1A1 and COL1A2 is implicated in numerous cancers, the differential role of COL1A1 in malignant, premalignant and normal tissues remains unclear, and its clinical significance in HCC has not been elucidated. In this study, using bioinformatics analysis of publicly-available HCC microarray data from Gene Expression Omnibus (GEO) and RNAseq data from The Cancer Genome Atlas (TCGA) database, we determined that COL1A1 is significantly upregulated in HCC tumor tissues in comparison to normal tissues. Our analysis also revealed that COL1A1 confers survival advantage and enhanced oncogenicity on HCC cells. Interestingly, the siRNA-mediated silencing of COL1A1 expression (siCOLIA1) suppressed HCC cells clonogenicity, motility, invasiveness and tumorsphere formation. Concomitantly, siCOL1A1 abrogated Slug-dependent epithelial-to-mesenchymal transition (EMT) and HCC stemness gene-signature, by attenuating expression of stemness markers SOX2, OCT4 and CD133. The present study provides some mechanistic insight into COL1A1 activity in HCC and highlights its putative role as an important diagnostic biomarker and potential therapeutic target in early development and metastasis of HCC.

AB - Increasing evidence shows that hepatocellular carcinoma (HCC) is a principal cause of cancer-related mortality globally, especially among Asian and African populations. Collagen type I α1 (COL1A1) is the major component of type I collagen. While aberrant expression of COL1A1 and COL1A2 is implicated in numerous cancers, the differential role of COL1A1 in malignant, premalignant and normal tissues remains unclear, and its clinical significance in HCC has not been elucidated. In this study, using bioinformatics analysis of publicly-available HCC microarray data from Gene Expression Omnibus (GEO) and RNAseq data from The Cancer Genome Atlas (TCGA) database, we determined that COL1A1 is significantly upregulated in HCC tumor tissues in comparison to normal tissues. Our analysis also revealed that COL1A1 confers survival advantage and enhanced oncogenicity on HCC cells. Interestingly, the siRNA-mediated silencing of COL1A1 expression (siCOLIA1) suppressed HCC cells clonogenicity, motility, invasiveness and tumorsphere formation. Concomitantly, siCOL1A1 abrogated Slug-dependent epithelial-to-mesenchymal transition (EMT) and HCC stemness gene-signature, by attenuating expression of stemness markers SOX2, OCT4 and CD133. The present study provides some mechanistic insight into COL1A1 activity in HCC and highlights its putative role as an important diagnostic biomarker and potential therapeutic target in early development and metastasis of HCC.

KW - COL1A1

KW - EMT

KW - Hepatocellular carcinoma

KW - Metastasis

KW - Stemnessk

UR - http://www.scopus.com/inward/record.url?scp=85070566371&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070566371&partnerID=8YFLogxK

U2 - 10.3390/cancers11060786

DO - 10.3390/cancers11060786

M3 - Article

AN - SCOPUS:85070566371

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 6

M1 - 786

ER -