Lin28/let-7 axis in breast cancer

Let-7 microRNAs are tumor suppressor microRNAs, and their reduced expression frequently occurs in various types of cancers, including breast cancer. A notable correlation exists between decreased let-7 microRNA levels and the overexpression of Lin28A and Lin28B, particularly in breast cancer cases with poor prognoses. Dysregulation of Wnt signaling significantly contributes to the upregulation of Lin28A and Lin28B in breast cancer. Both Lin28A and Lin28B operate from different cellular compartments to inhibit the biogenesis of let-7 microRNAs, which are essential for the post-transcriptional regulation of genes involved in key cellular functions such as proliferation, differentiation, and apoptosis. Decreased expression of let-7 microRNAs leads to the overexpression of oncogenes such as K-ras, C-myc, and SOX-2 in breast cancer. Overexpression of Lin28A associated with reduced let-7 microRNA levels is observed in estrogen receptor positive, estrogen receptor negative, and human epidermal growth factor receptor 2 positive breast cancers, whereas Lin28B overexpression with reduced let-7 microRNA levels occurs specifically in triple negative breast cancer. This review aims to dissect the molecular interplay between Lin28A, Lin28B, and let-7 microRNAs, elucidating their roles in breast carcinogenesis, metastasis, and the development of resistance to conventional treatments like radiation and chemotherapy. Additionally, the review addresses potential therapeutic avenues offered by let-7 microRNAs or their mimics, as well as Lin28A and Lin28B inhibitors, in the treatment of breast cancer.