RNA-Binding Motif Protein 38 as a Potential Biomarker and Therapeutic Target in Cancer

Abstract

RNA-binding proteins (RBPs) act as a key factor in gene regulation by governing RNA metabolism. They contribute to the expression and functions of most RNAs by binding to them and forming complexes. RNA-binding motif protein 38 (RBM38), a member of the RBP family, alters the stability and translation of targeted mRNAs to affect various biological processes, such as cell proliferation, cell cycle arrest, and myogenic differentiation. RBM38 contains a highly conserved RNA recognition motif (RRM) consisting of two subunits, RNP1 and RNP2, which specifically bind to RNAs. Recent studies have revealed that RBM38 regulates the mRNA stability of several tumor-related genes, such as p53 , mdm2 , p63 , p73 , p21 , and c-Myc , by binding to their 3′ untranslated regions (3′ UTRs); thus, RBM38 modulates targeted gene expression and affects the biological processes of tumors. In addition, abnormal RBM38 expression in some malignant tumors and its correlation with prognosis have been documented in many studies, indicating its value for potential clinical applications. In this review, we present an overview of RBM38, specifically highlighting its relationship with tumor manifestation and development. A brief overview of the potential use of RBM38 in cancer therapy is also included to provide ideas for further research on RBM38.

RNF26 Promotes Pancreatic Cancer Proliferation by Enhancing RBM38 Degradation

“…11 RBM38, which contains a conserved RNA-binding motif, is involved in modulating the stability and translation of mRNA in cells. 12 To date, a number of studies have reported that RBM38 suppresses tumor growth or progression by regulating the mRNA stability of tumor-associated genes, such as c-Myc, 13 PTEN, 14 p53, 15 MDM2, 16 and p57. 8 Interestingly, there are several regulatory loops modulating tumor progression in cells; for example, c-Myc is found to transcriptionally regulate the expression of RBM38 and form c-Myc-RBM38 complexes in breast cancer cells.…”

“…Posttranscriptional regulation of mRNA is important for maintaining the homeostasis of cells 11 . RBM38, which contains a conserved RNA-binding motif, is involved in modulating the stability and translation of mRNA in cells 12 . To date, a number of studies have reported that RBM38 suppresses tumor growth or progression by regulating the mRNA stability of tumor-associated genes, such as c-Myc, 13 PTEN, 14 p53, 15 MDM2, 16 and p57 8 .…”

RNA binding Motif protein-38 regulates myocardial hypertrophy in LXR-α-dependent lipogenesis pathway

“…Consequently, its knock-out in mice has shown an elevation of p53 in various cells and tissues such as embryonic fibroblasts, thymus, and spleen, which contributed to their enhanced penetrance to tumors [ 27 ]. RBM38 binds to various genes such as p53, p21, GDF15, mdm2, HuR, and c-myc through their 3ʹUTR AU-rich elements [ 29 ]. RBM38 has also been reported as a critical splice factor of the cardiac, which plays a role in governing heart sarcomerogenesis by regulating the alternative protein isorforms expressions [ 12 ].…”

Research progress on RNA−binding proteins in breast cancer

“…Studies have shown that ectopic expression of RBM38 can inhibit the proliferation of breast cancer cells, while knockdown of RBM38 exhibits an opposite effect in vivo and in vitro ( 52 ). When RBM38 is overexpressed, it inhibits the migration and invasion of breast cancer cells by inducing cell cycle arrest and inhibiting mutant p53-induced epithelial-mesenchymal transition (EMT) ( 5 ). EMT is triggered by individual extracellular signals, including extracellular matrix components, such as collagen and hyaluronic acid, and soluble growth factors, like transforming growth factor–β (TGF-β), fibroblast growth factor (FGF), and epidermal growth factor (EGF).…”