COL1A1 and Colorectal Cancer

COL1A1 mRNA is upregulated in CRC tissues and cells

COL1A1 was identified to be significantly upregulated in CRC tissues compared with adjacent tissues based on the Oncomine microarray dataset, which is a web-based data-mining platform. In the Oncomine database, all the CRC chip results were upregulated.

Figure 1. Expression levels of COL1A1 mRNA in CRC tissues and cell lines.
(International Journal of Oncology 2018)

Inhibition of COL1A1 suppresses proliferation

The cell proliferation assay demonstrated that inhibition of COL1A1 significantly decreased the proliferation of Caco2 and SW480 cells.

Bioinformatics analysis of NEK2 expression level and function.

NIMA related kinase 2 (NEK2) was upregulated in CRC tissues compared with adjacent tissues based on the Oncomine microarray dataset. These results suggested that NEK2 may serve a role in tumor proliferation and metastasis, but that it does not promote metastasis by dissolving matrix components.

These antibodies cetuximab and panitumumab for the treatment of advanced CRC. These antibodies target human EGFR. Initially, these targeted drugs were used in all patients with CRC, but it was later noted that only KRAS^WT patients respond well to treatment, whereas in KRAS^MUT patients the application of antibodies may be not only ineffective, but also harmful. Since the proportion of KRAS^MUT patients is ~40%, it is important to explore novel drug targets for CRC. A total of 294 commonly upregulated genes outside of the KRAS pathway were identified in the study. These genes serve as a pool of potential uniformly effective therapy targets for CRC. The result of GO and KEGG analyses demonstrated that the DEGs were enriched for genes involved in cell proliferation, signal transduction and tumor pathways. COL1A1 was significantly upregulated in CRC tissue compared with adjacent tissue. No significant association was identified between COL1A1 expression and age, sex or tumor size following analysis of the clinicopathological data of patients with CRC. However, the expression was significantly associated with serosal infiltration, lymph node metastasis and hematogenous metastasis. COL1A1 was demonstrated to promote CRC cell migration in vitro. Thus, researcher hypothesized that COL1A1 may be involved in the proliferation, invasion and metastasis of CRCs. The drug target, NEK2, as a hub gene is also of interest. siRNAs are not widely used in clinical treatment currently; thus, drugs targeting NEK2 may be more practical at present. NEK2 may serve a role in CRC proliferation and metastasis, but may not promote metastasis by dissolving matrix components. In conclusion, COL1A1 and NEK2 as therapeutic gene targets may result in improved therapeutic outcomes in KRAS^WT and KRAS^MUT patients with CRC.