Various LncRNA Mechanisms in Gene Regulation Involving miRNAs or RNA-Binding Proteins in Non-Small-Cell Lung Cancer: Main Signaling Pathways and Networks

Abstract

Long non-coding RNAs (lncRNAs) are crucial players in the pathogenesis of non-small-cell lung cancer (NSCLC). A competing binding of lncRNAs and mRNAs with microRNAs (miRNAs) is one of the most common mechanisms of gene regulation by lncRNAs in NSCLC, which has been extensively researched in the last two decades. However, alternative mechanisms that do not depend on miRNAs have also been reported. Among them, the most intriguing mechanism is mediated by RNA-binding proteins (RBPs) such as IGF2BP1/2/3, YTHDF1, HuR, and FBL, which increase the stability of target mRNAs. IGF2BP2 and YTHDF1 may also be involved in m6A modification of lncRNAs or target mRNAs. Some lncRNAs, such as DLGAP1-AS2, MALAT1, MNX1-AS1, and SNHG12, are involved in several mechanisms depending on the target: lncRNA/miRNA/mRNA interactome and through RBP. The target protein sets selected here were then analyzed using the DAVID database to identify the pathways overrepresented by KEGG, Wikipathways, and the Reactome pathway. Using the STRING website, we assessed interactions between the target proteins and built networks. Our analysis revealed that the JAK-STAT and Hippo signaling pathways, cytokine pathways, the VEGFA-VEGFR2 pathway, mechanisms of cell cycle regulation, and neovascularization are the most relevant to the effect of lncRNA on NSCLC.

Research Progress of Long Non-Coding RNA in Tumor Drug Resistance: A New Paradigm

“…Increased YAP expression results in drug resistance and metastasis. 50 LncRNA FENDRR (The FOXF1 Adjacent Noncoding Developmental Regulatory RNA) shows low expression in NSCLC and inhibits tumor growth. FENDRR enhancement inhibited chemotherapy resistance of A549/DDP cells to DDP.…”

HAMP predicts a pivotal role in modulating the malignant behaviors of non-small cell lung cancer cells

“…An accumulating body of data hints at the potential of lncRNAs to function as modulators in nearly every cellular process and are intricately intertwined with physiological shifts within organisms and a spectrum of disorders, encompassing malignancies [ 12 – 14 ]. The study of lung cancer-related lncRNAs is still an emerging field, and only a few lncRNAs, such as the lncRNA MALAT1 [ 15 ], the lncRNA UCA1 [ 16 ], the lncRNA HNF1A-AS1 [ 17 ], and the lncRNA PVT1 [ 18 ], have been proven to exert biological function and clinical significance. Understanding the functional roles and operational mechanisms of these lncRNAs within the context of NSCLC progression may provide insight into pioneering therapeutic approaches and the detection of plausible diagnostic and prognostic indicators.…”