RHO GTPase-Related Long Noncoding RNAs in Human Cancers

SIMPLE SUMMARY: Whilst mutations in genes encoding RHO GTPase proteins are rare in different type of cancers, altered expression of several RHO GTPases has been reported in a variety of human malignancies. As key regulators of gene expression, lncRNAs coordinate a wide range of molecular processes, including post-translational regulation through miRNA sponging. The purpose of the present study was to address the current state of knowledge about the lncRNAs involved in the regulation of the expression of the RHO GTPases including RHOA, RHOB, RHOC, RAC1, and CDC42, with a specific focus on the regulatory mechanism of lncRNAs as the molecular sponges of miRNAs. Considering the critical roles of lncRNAs in malignancies, lncRNA-based therapeutics are representing promising approaches in cancer treatment through novel technologies. In this regard, well-characterized examples of lncRNAs associated with tumorigenicity present experimental frameworks for future studies in this rapidly evolving field. ABSTRACT: RHO GTPases are critical signal transducers that regulate cell adhesion, polarity, and migration through multiple signaling pathways. While all these cellular processes are crucial for the maintenance of normal cell homeostasis, disturbances in RHO GTPase-associated signaling pathways contribute to different human diseases, including many malignancies. Several members of the RHO GTPase family are frequently upregulated in human tumors. Abnormal gene regulation confirms the pivotal role of lncRNAs as critical gene regulators, and thus, they could potentially act as oncogenes or tumor suppressors. lncRNAs most likely act as sponges for miRNAs, which are known to be dysregulated in various cancers. In this regard, the significant role of miRNAs targeting RHO GTPases supports the view that the aberrant expression of lncRNAs may reciprocally change the intensity of RHO GTPase-associated signaling pathways. In this review article, we summarize recent advances in lncRNA research, with a specific focus on their sponge effects on RHO GTPase-targeting miRNAs to crucially mediate gene expression in different cancer cell types and tissues. We will focus in particular on five members of the RHO GTPase family, including RHOA, RHOB, RHOC, RAC1, and CDC42, to illustrate the role of lncRNAs in cancer progression. A deeper understanding of the widespread dysregulation of lncRNAs is of fundamental importance for confirmation of their contribution to RHO GTPase-dependent carcinogenesis.