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.