Expression and interaction of RNA binding protein HuR with multidrug transporters (P-GP, MRP1, and ABCG2) in chemoresistant breast and colorectal cancer cells.

BACKGROUND: Chemoresistance poses a significant challenge in cancer treatment. Over expression of efflux pumps is one of the primary mechanisms that confer chemoresistance. P-GP, MRP1, and ABCG2, which are important ABC efflux pumps, collectively facilitate the transportation of a wide range of chemotherapeutic drugs out of cells. HuR is known to regulate the expression of various oncogenes through several ways, such as enhancing mRNA trafficking, facilitating mRNA stabilization, and protein translation. This study aimed to investigate the expression pattern of HuR as well as the co-expression pattern of ABC transporters (P-GP, MRP1, and ABCG2) with HuR in chemoresistant breast and colorectal cancer tissues to gain insights into the mechanisms of chemoresistance. METHODS: Immunofluorescence imaging as well as bioinformatic tools were used in this study to understand the expression and co-expression patterns of HuR protein and P-GP, MRP1, and ABCG2 in paired case-control chemoresistant samples. RESULTS: A substantial difference was observed in the level of HuR expression between chemoresistant and control tissues obtained from breast and colorectal cancer patients. The mean relative HuR expression in breast and colorectal chemoresistant tissues was 19.2 and 5.29 times greater, respectively, compared to control tissues. Linear regression analysis revealed that the expression of the ABC efflux transporters (P-GP, MRP1, and ABCG2) is proportional to HuR protein expression in chemoresistant breast and colorectal cancer tissues. Molecular docking analyses between RNA recognition motif (RRM) of the HuR protein and AU-rich elements (ARE) from the 3'UTR of P-GP, MRP1, and ABCG2 mRNA suggested stable binding of HuR to the 3'UTR of the three ABC transporters. CONCLUSION: The observed overexpression of HuR in chemoresistant tissues suggests its association with chemoresistance mechanisms. Besides, HuR might facilitate posttranscriptional mRNA stabilization of P-GP, MRP1, and ABCG2, which makes it a potential therapeutic target to improve treatment outcomes in chemoresistant patients.