The crosstalk between long non-coding RNAs and PI3K in cancer

Abstract

Long non-coding RNAs (lncRNAs) are able to positively or negatively regulate other genes expression in cis or in trans. Their effect can be achieved through RNA-protein, RNA-DNA, or RNA-RNA interactions. They can recruit transcription factors and act as scaffolds or guides for chromatin-modifying enzymes. PI3K kinases transform external stimuli to intracellular signals regulating cell growth, differentiation, proliferation, survival, intracellular trafficking, cytoskeletal changes, cell migration and motility, and metabolism. PI3K is activated in cancer and affects several aspects of oncogenesis. LncRNAs and PI3K have been shown to be interconnected in several different cancer subtypes enhancing aberrant cell proliferation, epithelial-to-mesenchymal transition, migration and invasion, and also cancer cell metabolism. In this review, we have assembled recent data describing the interaction between lncRNAs and PI3K and the results of such interaction.

Targeting PI3K in cancer: mechanisms and advances in clinical trials

“…In physiologic conditions, PI3K is normally activated by a variety of extracellular stimuli, such as growth factors, cytokines, and hormones [13]. Upon activation, PI3K catalyzes the phosphorylation of PtdIns(4,5) P2(PIP2) to produce PtdIns (3,4,5) P3(PIP3), a second messenger that binds and recruits a subset of pleckstrin-homology (PH), FYVE, Phox (PX), C1, C2 or other lipid-binding domains of downstream targets to the cell membrane. A variety of signaling proteins, such as kinases AKT and PDK1 can bind to the lipid products of PI3K and thereby localize to the cell membrane to activate cell growth and cell survival pathways [14].…”

“…In the last decade or so, ncRNAs have emerged as important regulators of a wide range of genes and PI3K/ AKT/mTOR pathway [5,6]. ncRNAs function as both upstream mediators and downstream effectors to affect PI3K pathway activities.…”

“…MicroRNA (miRNA) and long non-coding RNA (lncRNA), the two most studied classes of non-coding RNA (ncRNA), are crucial regulators of gene expression [4]. These two types of ncRNA and PI3K/AKT/mTOR pathway are in tight conjunction during oncogenesis [5,6]. The PI3K/AKT/mTOR pathway has been found to be dysregulated almost in all human cancers, such as breast cancer, colorectal cancer, and hematologic malignancies, which emphasizes the value of targeting this pathway as a potential therapeutic direction in the treatment of cancer [7].…”

Long Noncoding RNA Taurine-Upregulated Gene1 (TUG1) Promotes Tumor Growth and Metastasis Through TUG1/Mir-129-5p/Astrocyte-Elevated Gene-1 (AEG-1) Axis in Malignant Melanoma

“…They seem to be mRNAs in structure, but do not encode proteins [ 5 ]. LncRNAs have been considered to exert essential functions in tumorigenesis and procession of a few malignant tumors [ 6 ]. Taurine-upregulated gene1 (TUG1) is a transcript upregulated by taurine [ 7 ].…”

Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications

“…Specifically, evidence to date demonstrates that lncRNAs are frequently aberrantly expressed in human cancers in which they may serve as oncogenes or tumor suppressors[ 73 , 74 ]. These lncRNAs can mediate several cancer-associated processes, including epigenetic regulation, the DNA damage response, cell cycle control, and miRNA silencing[ 75 ]. Furthermore, dysregulated lncRNAs can disrupt multiple cellular oncogenic pathways by exerting oncogenic and/or tumor suppressive functions.…”