LINC02159 promotes non-small cell lung cancer progression via ALYREF/YAP1 signaling

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cancer development and progression, and as promising biomarkers for the diagnosis and prognosis of cancer. In this study, we identified a new lncRNA (LINC02159) that was upregulated in the tumor tissues and serum of non-small cell lung cancer (NSCLC) patients. We demonstrated that knockdown of LINC02159 inhibited NSCLC cell proliferation, migration, and invasion, but induced cell apoptosis and cell cycle arrest in vitro and retarded tumor growth in vivo, while overexpression of LINC02159 led to the opposite effect. We discovered that LINC02159 was highly correlated with cancer growth and metastasis-related pathways by using transcriptomic analysis and that YAP1 was a potential target gene of LINC02159. Mechanistically, LINC02159 bound to the Aly/REF export factor (ALYREF) to enhance the stability of YAP1 messenger RNA (mRNA) via m5C modification, which led to the overexpression of YAP1 and the activation of the Hippo and β-catenin signaling pathways in NSCLC cells. Rescue experiments showed that LINC01259 promoted NSCLC progression in a YAP1- and ALYREF-dependent manner. In conclusion, LINC02159 plays an oncogenic role in NSCLC progression by regulating ALYREF/YAP1 signaling, and it has the potential to be utilized as a diagnostic marker and therapeutic target for NSCLC.

NOP2 facilitates EZH2-mediated epithelial–mesenchymal transition by enhancing EZH2 mRNA stability via m5C methylation in lung cancer progression

“…ALYREF, an important m5C reader, has been proven to maintain mRNA stability [ 20 – 22 ]. To verify whether ALYREF is a functional m5C reader in lung cancer cells, we performed RIP assay with ALYREF antibody in H1650 and H1299 cells, and the RT-qPCR results showed that ALYREF could bind to EZH2 mRNA, suggesting that ALYREF might be the m5C reader (Fig.…”

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

“…LncRNAs not only regulate gene expression and participate in signal transduction pathways but also regulate epigenetic, transcriptional, and post-transcriptional modifications [ 45 ]. LncRNA expression is closely related to a variety of biological functions, including cell survival, cancer progression and metastasis [ 46 , 47 ]. Recent studies have shown that abnormal expression levels of lncRNAs are closely related to the pathology and prognosis of glioma [ 48 ].…”

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)

“…In vitro and in vivo studies have identifiedthe RNA methyltransferase NSUN2 as primarily enzyme catalyzing m5C production in mRNAs, with m5C specifically recognized by the mRNA export adaptor ALYREF [ 46 ]. Recent research has linked ALYREF to the development of various tumors, including bladder cancer [ 47 , 48 ], breast cancer [ 49 ], neuroblastoma [ 50 ], hepatocellular carcinoma [ 51 , 52 ], glioblastoma [ 53 ], and non-small cell lung cancer [ 54 ]. These findings underscore the gene’s critical role in human cancer.…”