Zahra Ghaemi - Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IraN
Bahram M.Soltani - Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IraN
Seyed Javad Mowla - Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IraN

The HER signaling pathway is one of the major pathways associated with various cancers, including breast cancer. The pathway contains four cell surface receptors: ErbB1/ EGFR, ErbB2/HER2, ErbB3, and ErbB4. ErbB4, as one of the HER receptors, activates several intracellular pathways via their capability to interact with numerous signal transducers and influences the variety of cellular processes.Some of the varied functions of ERBB4 could be mediated by a microRNA embedded within the gene. MicroRNAs act as post-transcriptional regulators of gene expression and their dysregulation affect signaling pathways in carcinogenesis. The objective of this study was to introduce a novel miRNA as a possible regulator of HER signaling pathway. Methods RNAfold and Mfold online tools were employed to search for possible microRNA hairpin structures within the gene. Conservation status of the ERBB4-miR1 and its precursor sequence was examined using blat search for human genome and other organisms in UCSC database. For miRNA expression analysis, Sequence Read Archive (SRA) was evaluated in different human cell lines and tissue. CID-miRNA was used for prediction of Drosha processing sites. The genomic fragment containing ERBB4-premir1 was cloned into PEGFP-C1 vector and the human cell lines were transfected with the vector. To evaluate endogenous and exogenous expression level of ERBB4-miR1 in human cell lines and breast tumors, RT-qPCR method was used.Results and Discussion Predicted miRNA expression was evaluated in different breast cell lines and tumors to verify its endogenous expression. Furthermore, Overexpression of ERBB4-premir1 vector in human cell lines resulted in production of mature exogenous ERBB4-miR1 that represents the successful processing of predicted miRNA precursor. The results along with bioinformatics data introduce ERBB4-miR1 as a novel miRNA encoded within the ERBB4 gene. Hence, deregulation of ERBB4-miR1 might play a pivotal role in malignancies through its effect on HER signaling pathway but more experimental validation of methods are needed to uncover ERBB4-mir1 role in HER signaling pathway regulation and breast cancer.

ERBB4, microRNA discovery, HER signaling, Breast Cancer