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 language | English |
|---|---|
| Article number | 786 |
| Journal | Cancers |
| Volume | 11 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2019 |
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Keywords
- COL1A1
- EMT
- Hepatocellular carcinoma
- Metastasis
- Stemnessk
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Collagen 1A1 (COL1A1) is a reliable biomarker and putative therapeutic target for hepatocellular carcinogenesis and metastasis. / Ma, Hon Ping; Chang, Hang Lung; Bamodu, Oluwaseun Adebayo; Yadav, Vijesh Kumar; Huang, Ting Yi; Wu, Alexander T.H.; Yeh, Chi Tai; Tsai, Shin Han; Lee, Wei Hwa.
In: Cancers, Vol. 11, No. 6, 786, 01.06.2019.Research output: Contribution to journal › Article
}
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 -