piRNAs and PIWI-like proteins in cancer and their future as biomarkers and therapy targets in breast cancer

Abstract

Globally, breast cancer (BC) is the most common type of cancer, with 2.296.840 new cases in 2020 with almost 700.000 related deaths. Due to the high burden this represents, it is imperative to expand horizons to be able to find novel biomarkers and therapeutic targets that can be used to improve prognosis, treatment, and survival of breast cancer patients. In recent years, numerous studies have been conducted looking for the association between piRNAs (PIWI – interacting RNAs) and the development, pathogenesis, metastasis, and progression of different types of cancer, including BC. PiRNAs are small molecules (24-31 nucleotides) that interact with the PIWI-protein complex (PIWI-like proteins - HIWI/HILI in humans) performing regulatory functions by inducing transcriptional, post-transcriptional, translational, and post-translational epigenetic changes, which has been observed to contribute to cancer development through modifications in cell proliferation, transposon silencing, genome rearrangement, epigenetic regulation, protein regulation, and stem cell maintenance. In breast cancer, a strong association has been found between the expression of some piRNAs, PIWI-like proteins and tumor development. If a specific piRNA could be associated with a distinct type of cancer, it could then be used as an early biomarker which would allow for a better prognosis. Findings surrounding these molecular mechanisms could also spark interest in studies focusing on the modification of the expression of piRNAs in cancer cells. In this article, we intend to review in a straightforward manner the current information about piRNAs/PIWI-like proteins focusing on their expression in BC.