The inhibitory effects of COL1A2 on colorectal cancer cell proliferation, migration, and invasion

J Cancer. 2018 Jul 30;9(16):2953-2962. doi: 10.7150/jca.25542. eCollection 2018.

Abstract

Purpose: Collagen type I alpha 2 chain (COL1A2) has been shown to participate in the development of various human malignancies. However, the role of COL1A2 in human colorectal cancer (CRC) remains unknown. This study investigated the expression pattern of COL1A2 in primary CRC tissues as well as the correlation of COL1A2 expression with clinicopathological features and prognosis of CRC. The function of COL1A2 in CRC cell proliferation, migration, and invasion as well as the possible mechanisms were also examined. Methods: Real-time PCR and immunohistochemical analysis were performed to determine the expression of COL1A2 in primary cancer tissues and adjacent normal tissues from CRC patients. A COL1A2-expressing lentiviral vector was transfected into CRC cells, and cell counting kit-8 and Transwell assays were used to explore the effects of COL1A2 on CRC cell proliferation, migration, and invasion. Microarray-based mRNA expression profile screening was performed to reveal the possible signaling pathways involved in COL1A2-regulated cell behaviors. Results: COL1A2 was significantly downregulated in primary CRC tissues. The mRNA levels of COL1A2 in CRC tissues were correlated with tumor differentiation, invasion, and lymph node metastasis. Overexpression of COL1A2 inhibited proliferation, migration, and invasion of CRC cell lines (SW480 and SW620). The microarray analysis showed that COL1A2 overexpression regulated numerous oncogenes and cancer-related signaling pathways. Among them, altered expression of ten representative cancer-related genes in these pathways were further confirmed by western blotting. Conclusions: Our study identified COL1A2 as a novel tumor suppressor in CRC and provided a potential therapeutic approach to treat CRC.

Keywords: Collagen type I alpha 2 chain; colorectal cancer; invasion; microarray; migration; proliferation.