MicroRNA-190b Targets RFWD3 in ER Positive Breast Cancer

Abstract

Background: In the year 2020 breast cancer was the most common form of cancer. Roughly 70% of breast cancers are estrogen receptor positive. MicroRNA-190b has previously been reported to be up-regulated in estrogen receptor positive breast cancers. Our group has previously demonstrated that microRNA-190b is hypomethylated in ER+ breast cancers, potentially leading to its upregulation. Results: In this study, using data from the Cancer Genome Atlas, we confirm that microRNA-190b is overexpressed in breast cancer via differential expression analysis and show that high expression of microRNA-190b results in more favorable outcomes in Luminal A patients (HR=0.29, 95% CI 0.12-0.71, P value=0.0063). MicroRNA190b target analysis, using immunoprecipitation of biotin labelled microRNA-190b, followed by RNA sequencing, identified RFWD3 as one of microRNA-190b’s regulatory targets in estrogen receptor positive breast cancer. Survival analysis of RFWD3 showed that elevated levels result in poorer overall survival in Luminal A breast cancer patients (HR = 2.22, 95% CI 1.33-3.71, P = 0.002). Gene ontology analysis of our sequencing results indicate that miR-190b may have a role in breast cancer development and/or tumorigenesis and that it may be a suitable tool in characterization between the estrogen receptor positive subtypes, Luminal A and Luminal B.Conclusions: We show that miR-190b targets RFWD3 in ER+ breast cancers leading to lower RFWD3 protein expression. Low levels of RFWD3 are associated with better outcomes in Luminal A breast cancer patients but not in Luminal B patients.