MicroRNAs (miRNAs) are a family of short (~20-23 nucleotides), endogenous, evolutionary conserved, single-stranded RNA molecules that regulate gene expression in a sequence-specific manner (1). Dysregulated miRNA expression is involved in the initiation and progression of certain types of cancer (2, 4). The expression of microRNA‑616 (miR-616) has been shown to be upregulated in androgen-independent prostate cancer (2, 3), and a few other cancers. Ye et al. reported that miR-616-3p inhibited cell growth and mammosphere formation of breast cancer cells by suppressing GLI1 (4), while Yuan reported that miR-616-3p promoted breast cancer cell migration and invasion by targeting TIMP2 and regulating MMP signalling (5). Additional studies are warranted to further investigate the role of miR-616 in breast cancers.
We hypothesize that miR-616 can function either as oncogene or tumour suppressor in the different subtypes of human breast cancers. Preliminary data from the Gupta Group shows that: expression of miR-616 was reduced in paired tumour and adjacent normal tissues in breast cancer. Furthermore, increased expression of miR-616 is associated with poor outcome in Luminal A subtype (ER+, PR+, HER-) and good outcome in the HER2-enriched subtype of breast cancer.
The main aim of this project is to functionally characterize the role of miR-616 in different subtypes of breast cancer. The objectives of the project are:
Objective 1: Generate a panel of breast cancer cell lines [ER-positive, HER2-enriched and TNBC cells] with gain-of-function and loss-of-function of miR-616.
Objective 2: Determine the effects of miR-616 on cell growth, migration and invasion of ER-positive, HER2-enriched and TNBC cells.
The results will provide rationale for developing strategies to modulate miR-616 expression to counteract tumour growth and to improve responsiveness to standard therapies in breast cancer. In addition, if miR-616 is elucidated to act as an oncogene it could act as a potential biomarker for breast cancer.
