Competitive Endogenous Role of the LINC00511/miR-185-3p Axis and miR-301a-3p From Liquid Biopsy as Molecular Markers for Breast Cancer Diagnosis

1. Introduction 1.1. Background: Breast cancer is one of the leading causes of death for women globally, according to the world health organization (WHO), the number of cancer cases expected in 2025 will be 19.3 million cases. In Egypt, cancer is an increasing problem and especially breast cancer [1].

Breast cancer is the most common female malignant tumor and a major threat to women's health and its development is considerably aggressive local invasion, early metastases, and multidrug resistance to chemotherapy [2, 3]. Therefore, developments of minimally-invasive markers for early detection of breast cancer are of great interest.

The cancer genome Atlas (TCGA) revealed that many of the mutations and copy number changes found in cancer do not overlap with protein coding genes [4], but are frequently located in non-coding DNA-including non-coding RNA genes [5]. MicroRNAs (miRNAs) were among the first non-coding RNAs to be investigated cancer, and their roles as therapeutic targets or biomarkers in cancer [6].

MiRNAs are short, single-stranded RNA sequences (usually 19-23 nucleotides) that control gene expression in a variety of physiological and developmental process, thus having a critical role in posttranscriptional regulation of gene expression in a broad range of biological systems [7, 8]. MiRNAs mediate the repression of target mRNA by base pairing to complementary sequence in the 3'-UTR, causing transcript destabilization, translational repression or both [9]. It has been reported that miRNAs also modulate gene expression by binding to other regions, including protein-coding exons [10], and can even induce gene expression in mammalian cells [11].

Cell-free circulating miRNAs usually exist bound to ribonucleoprotien complexes or high-density lipoprotein or they are released from cells in lipid vesicles, micro-vesicles, exosomes or apoptotic bodies [12-15].Thus, circulating miRNAs may reflect homeostatic response of the organism, as well as signs of disease progression. Owing to their stability and resistance to endogenous RNAse activity, these miRNAs have been proposed as diagnostic and prognostic biomarkers for diseases, including cancer [16].