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
Authors: Jianjun Liu
Li Zhao
Mingming Jin
Fei Xu
Baoming Mi
Gang Huang
Tian Li
Qian Hua
Journal: Journal of hematology & oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: LINC01123; Long non-coding RNAs; aerobic glycolysis; c-Myc; non-small cell lung cancer.
Affiliations: Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China., Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China., Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University (Wuxi 4th People's Hospital), Wuxi, 214062, Jiangsu, China., Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China. ., Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China. .

Abstract:  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 18F-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. 

Retracted: No

PubPeer comments:
  Figure 7, similar colonies under different conditions , 
 #1 Thanks for pointing the error! As you have pointed, in Figure 7B, the forth colony seems quite similar with the fifth colony, which probably due to our mistake during figure assembly. The corrected Figure 7B is attached below. We sincerely apologize for this unintentional error made before manuscript submission.  ,