Integrated High-Throughput Bioinformatics (Microarray, RNA-Seq, and RNA Interaction) and qRT-PCR Investigation of BMPR1B Axis as a Potential Diagnostic Biomarker of Isfahan Breast Cancer.

Background: According to the bioinformatics analyses and previous studies, bone morphogenetic protein receptor type 1B (BMPR1B) dysregulation could remarkably affect breast cancer (BC) status as a potential biomarker and tumor suppressor. Therefore, the analysis of the expression level of BMPR1B and other relevant biological factors such as microRNAs, long non-coding RNAs, downstream proteins in the relevant signaling pathways, and finding the accurate biological mechanism of BMPR1B could be helpful for a better understanding of BC pathogenicity and discovering the new treatment methods and drugs.

Materials and methods: R Studio software (4.0.2) was used for microarray data analyses. GSE31448 dataset was downloaded by GEOquery package and analyzed by limma package. STRING and miRWalk online databases and Cytoscape software were used for interaction analyses. Quantitative measurement of BMPR1B expression level was performed by qRT-PCR experiment.

Result: Microarray and real-time PCR analysis revealed that BMPR1B has a significant downregulation in the transforming growth factor (TGF)-beta and bone morphogenic protein (BMP) signaling pathways in BC samples. BMPR1B is a potential diagnostic biomarker, regulated by hsa-miR-181a-5p. Also, BMPR1B regulates the function of BMP2, BMP6, SMAD4, SMAD5, and SMAD6 proteins.

Discussion: BMPR1B have a significant role in the development of BC by regulating the potential proteins' function, playing the diagnostic biomarker role, and regulation of TGF-beta and BMP signaling pathways. The high amount of BMPR1B protein helps in increasing the survival rate of the patients.