Journal Article

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

Xu, Jing, Wang, Maoye, Zhang, Xiaoxin, Zhang, Xu, Gu, Jianmei, Zhang, Jiahui, Yang, Qiurong, Yu, Dan, Li, Yixin, Chen, Yanke

2023

Overview

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 m 5 C 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: ALYREF / Apoptosis / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cancer therapies / Carcinoma, Non-Small-Cell Lung - pathology / Cell cycle / Cell Line, Tumor / Cell migration / Cell Movement - genetics / Cell proliferation / Cell Proliferation - genetics / Development and progression / Gene expression / Gene Expression Regulation, Neoplastic / Health aspects / Humans / Immunotherapy / Kinases / LncRNA / Lung cancer / Lung cancer, Non-small cell / Lung cancer, Small cell / Lung Neoplasms - pathology / m5C modification / Mass spectrometry / Medical prognosis / Metastases / Metastasis / mRNA stability / Non-coding RNA / Non-small cell lung carcinoma / NSCLC / Nuclear Proteins - genetics / Oncology / Penicillin / Plasmids / Progression / Proteins / RNA / RNA modification / RNA, Long Noncoding - metabolism / RNA-Binding Proteins - metabolism / Scientific imaging / Signal Transduction / Small cell lung carcinoma / Statistical analysis / Therapeutic targets / Transcription Factors - genetics / Transcription Factors - metabolism / Transcriptomics / Tumors / YAP1 / Yes-associated protein / β-Catenin