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
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
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LINC01123是c-Myc激活的长非编码RNA，通过miR-199a-5p/c-Myc轴促进非小细胞肺癌的增殖和有氧糖酵解
DOI：
10.1186/s13045-019-0773-y
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发表时间：
2019-09-05
影响因子：
28.5
通讯作者：
Huang, Gang
中科院分区：
文献类型：
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作者：
Hua, Qian;Jin, Mingming;Huang, Gang
长链非编码rna （lncRNAs）与非小细胞肺癌（NSCLC）有关，但其在介导有氧糖酵解中的特定作用的潜在分子机制尚不清楚。方法采用新一代RNA测序技术，鉴定高18f -氟脱氧葡萄糖（FDG）摄取的NSCLC组织与邻近正常肺组织之间的差异表达RNA。采用实时荧光定量PCR和原位杂交（ISH）法检测LINC01123在NSCLC组织中的表达。通过体外和体内功能实验确定LINC01123在细胞生长和有氧糖酵解能力中的生物学作用。此外，通过生物信息学分析、双荧光素酶报告基因试验和染色质免疫沉淀（ChIP）试验探索了LINC01123的转录。RNA免疫沉淀（RIP）和荧光素酶分析证实了LINC01123和c-Myc之间预测的竞争性内源性RNA （ceRNA）机制。结果通过RNA-seq分析，共鉴定出364个差异表达基因，其中LINC01123是过表达最多的lncrna之一。在扩大的NSCLC队列中进一步验证证实，LINC01123在92对NSCLC组织中上调，并与较差的生存率相关。功能实验显示，LINC01123促进NSCLC细胞增殖和有氧糖酵解。机制研究表明，LINC01123是c-Myc的直接转录靶点。同时，LINC01123通过海绵miR-199a-5p增加c-Myc mRNA的表达。此外，救援实验表明，LINC01123作为癌基因依赖于miR-199a-5p和c-Myc发挥作用。结论由于LINC01123在NSCLC中表达上调，与预后相关，并通过与c-Myc的正反馈回路控制增殖和有氧糖酵解，有望成为NSCLC的潜在生物标志物和治疗靶点。
BackgroundLong 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.MethodsNext-generation RNA sequencing assay was performed to identify the differentially expressed RNAs between NSCLC tissues with high18F-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.ResultsThree 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.ConclusionSince 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.