MicroRNAs Role in Breast Cancer: Theranostic Application in Saudi Arabia

Abstract

Breast cancer is an aggressive silent disease, representing 11.7% of the diagnosed cancer worldwide, and it is also a leading cause of death in Saudi Arabia. Consequently, microRNAs have emerged recently as potential biomarkers to diagnose and monitor such cases at the molecular level, which tends to be problematic during diagnosis. MicroRNAs are highly conserved non- coding oligonucleotide RNA. Over the last two decades, studies have determined the functional significance of these small RNAs and their impact on cellular development and the interaction between microRNAs and messenger RNAs, which affect numerous molecular pathways and physiological functions. Moreover, many disorders, including breast cancer, are associated with the dysregulation of microRNA. Sparingly, many microRNAs can suppress cancer cell proliferation, apoptosis, angiogenesis, invasion, metastasis, and vice versa. Remarkably, microRNAs can be harvested from patients' biofluids to predict disease progression that considered a non-invasive method. Nevertheless, MicroRNAs are currently utilized as anti- cancer therapies combined with other drug therapies or even as a single agents' treatment. Therefore, this review will focus on microRNAs' role in breast cancer as an indicator of disease progression. In addition, this review summarizes the current knowledge of drug sensitivity and methods in detecting microRNA and their application to improve patient care and identifies the current gaps in this field.

Keywords: Saudi Arabia; anticancer therapy; breast cancer metastasis; chemotherapy resistance; circulating biomarkers; miRNA; molecular pathways.

Figure 1

MiRNA biogenesis. miRNA genes or spliced introns are transcribed by polymerase II (Pol- II) as primary miRNA (pri-miRNA). The pri-miRNA is subsequently cleaved by Drosha along with DGCR8 proteins to generate the pre-miRNAs. The pre-miRNAs are then exported to the cytoplasm by Exportin-5 (XPO5) and cleaved again by DICER1 to form a short double- stranded miRNA. Together with Argonaute (AGO), this double-stranded miRNA is unwound into a mature miRNA (single strand) and loaded as a guide for the miRNA-induced silencing complex (miRISC) to target the UTRs or CDSs of the mRNA. Based on the mature RNA sequences, miRISC could repress mRNA expression. The mature miRNA can export from the cell and reaches the bloodstream as lipoproteins, exomes, microvesicles, and apoptotic bodies. Which can be used as a marker for cancer-based on their expression levels, UP or DW (down)—created with BioRender.com.

Figure 2

miRNA therapeutics and delivery methods. (A) showing the chemically modified oligonucleotide to sustain RNA stability. Such as, adding 2’-O-methyl group, linking the 2′-O atom and the 4′-C, or adding sulfur to phosphate group (phosphorothioate). (B) Methods that are used to increases RNA delivery (miRNA or RNAi). Using adenovirus, liposomes vehicles and synthetic polyethylenimine. Created with BioRender.com.

Figure 3

RNAi mechanisms. After transfecting the double strand RNA, it is cleaved by DICER to form a smaller double-stranded miRNA. Then loaded as a guide for the miRNA-induced silencing complex (miRISC) to target the mRNA. Created with BioRender.com.