THE ROLE OF TUG LONG NON-CODING RNA IN BREAST CANCER AND TYPE 2 DIABETES: A SYSTEMATIC REVIEW OF MOLECULAR MECHANISMS, REGULATORY NETWORKS, AND CLINICAL IMPLICATIONS

Abstract

Long non-coding RNAs (lncRNAs) are essential members of the human transcriptome that regulate all forms of gene expression during the body's normal and disease situations. The regulatory role of taurine upregulated gene 1 (TUG1) in gene expression has been established during tumor formation and the regulation of metabolism. In this review, we critically integrate findings from experimental models, patient-based studies, and bioinformatics analyses to clarify how TUG1 regulates molecular networks common to breast cancer and type 2 diabetes mellitus. Relevant information was extracted from PubMed, Scopus, and Web of Science databases following the PRISMA 2020 guidelines for systematic review. Relevant studies were considered to contain the expression of TUG1, regulation of TUG1, functional predictions, pathway(s) of signal transduction, and clinical aspects. Evidence from in vitro and in silico studies was combined and presented descriptively. TUG1 is known to regulate gene expression through epigenetic modifications, regulation of transcription, and post-transcriptional control processes, which involve specific microRNAs and their corresponding target genes. TUG1-associated gene networks involve main signaling pathways of cancer and metabolic diseases, including PI3K/AKT, MAPK, insulin signaling, inflammation, and cell cycle. Studies have shown that changes in TUG1 expression correlate with tumor progression, negative clinical impacts, insulin resistance, and chronic inflammation/ inflammatory processes. The studies reviewed here suggest that TUG1 operates at the crossroads of metabolic and cancer signaling pathways and, therefore, could be considered as a variable for the translational studies, and might be used as a marker and target for cancer diagnosis or therapy.