Abstract
OBJECTIVE: To investigate the expression level of HNRNP A1 in colorectal cancer (CRC) and its prognostic implications. METHODS: We investigated HNRNP A1 expression level in CRC using HPA, TIMER, and GEPIA databases and analyzed its association with Ki-67 and VEGFA expressions. Kaplan-Meier Plotter database was used to analyze the correlation of HNRNP A1 mRNA levels with the survival rates of CRC patients. Pathway enrichment analysis was performed for predicting the biological roles of HNRNP A1 in CRC progression. Immunohistochemistry and Western blotting were used to examine the protein levels of HNRNP A1 in CRC versus adjacent tissues, and TIMER was used for assessing its expression in the infiltrating immune cells. In RKO/Caco2 cells, the effects of lentivirus-mediated knockdown of HNRNP A1 on cell proliferation and migration were observed, and the inhibitory effect of VPC-80051 (a HNRNP A1 inhibitor) on cell proliferation was evaluated to assess its potential as a therapeutic agent. RESULTS: HNRNP A1 was significantly overexpressed in CRC tissues and correlated with a poor prognosis of the patients. HNRNP A1 expression level was correlated with the infiltrating immune cells in CRC microenvironment and positively correlated with MKI67 and VEGFA expressions in CRC. A high HNRNP A1 expression predicted a in survival and progression-free survival of CRC patients and was involved in multiple biological processes related with CRC progression. In RKO/Caco2 cells, HNRNP A1 knockdown significantly suppressed cell proliferation and migration, and treatment with VPC-80051 also effectively inhibited CRC cell proliferation. Immunohistochemical study demonstrated a close correlation of HNRNP A1 overexpression with tumor stage of CRC. CONCLUSION: HNRNP A1 is overexpressed in CRC tissues to modulate cell proliferation and migration and is correlated with a poorer prognosis. VPC-80051 can effectively inhibit CRC cell proliferation, suggesting the potential of HNRNP A1 as a therapeutic target for CRC.