Journal Article

LINC01123, a c-Myc-activated long non-coding RNA, promotes proliferation and aerobic glycolysis of non-small cell lung cancer through miR-199a-5p/c-Myc axis

Liu, Jianjun, Li, Tian, Zhao, Li, Jin, Mingming, Mi, Baoming, Huang, Gang, Hua, Qian, Xu, Fei

2019

Overview

Background Long non-coding RNAs (lncRNAs) have been associated with non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms of their specific roles in mediating aerobic glycolysis have been poorly explored. Methods Next-generation RNA sequencing assay was performed to identify the differentially expressed RNAs between NSCLC tissues with high 18 F-fluorodeoxyglucose (FDG) uptake and their adjacent normal lung tissues. LINC01123 expression in NSCLC tissues was measured by real-time PCR and in situ hybridization (ISH) assay. The biological role of LINC01123 in cell growth and aerobic glycolysis capability was determined by performing functional experiments in vitro and in vivo. Further, the transcription of LINC01123 was explored by bioinformatics analysis, dual-luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay. RNA immunoprecipitation (RIP) and luciferase analyses were used to confirm the predicted competitive endogenous RNA (ceRNA) mechanisms between LINC01123 and c-Myc. Results Three hundred sixty-four differentially expressed genes were identified in RNA-seq assay, and LINC01123 was one of the most overexpressed lncRNAs. Further validation in expanded NSCLC cohorts confirmed that LINC01123 was upregulated in 92 paired NSCLC tissues and associated with poor survival. Functional assays showed that LINC01123 promoted NSCLC cell proliferation and aerobic glycolysis. Mechanistic investigations revealed that LINC01123 was a direct transcriptional target of c-Myc. Meanwhile, LINC01123 increased c-Myc mRNA expression by sponging miR-199a-5p. In addition, rescue experiments showed that LINC01123 functioned as an oncogene depending on miR-199a-5p and c-Myc. Conclusion Since LINC01123 is upregulated in NSCLC, correlates with prognosis, and controls proliferation and aerobic glycolysis by a positive feedback loop with c-Myc, it is expected to be a potential biomarker and therapeutic target for NSCLC.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: aerobic glycolysis / Animals / Bioinformatics / c-Myc / c-Myc protein / Cancer Research / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - metabolism / Carcinoma, Non-Small-Cell Lung - pathology / CAT scans / Cell growth / Cell Line, Tumor / Cell proliferation / Cell Proliferation - physiology / Chromatin / Cohort Studies / Computational biology / Diagnosis / Gene expression / Genes / Glucose metabolism / Glycolysis / Hematology / Heterografts / Humans / Hybridization / Immunoprecipitation / LINC01123 / Long non-coding RNAs / Luciferase / Lung cancer / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Male / Medical prognosis / Medical schools / Medicine / Medicine & Public Health / Messenger RNA / Mice / Mice, Inbred BALB C / Mice, Nude / MicroRNAs - genetics / MicroRNAs - metabolism / Molecular modelling / Myc protein / Non-coding RNA / Non-small cell lung cancer / Non-small cell lung carcinoma / Oncology / Positron emission tomography / Prognosis / Property and casualty insurance / Proto-Oncogene Proteins c-myc - genetics / Proto-Oncogene Proteins c-myc - metabolism / Risk factors / RNA / RNA sequencing / RNA, Long Noncoding - biosynthesis / RNA, Long Noncoding - genetics / RNA, Long Noncoding - metabolism / Signal Transduction / Small cell lung cancer / Therapeutic applications / Transcription