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长链非编码RNA通过调控肺癌腺癌中-介导的表达抑制糖酵解和肿瘤进展。

Long Noncoding RNA Suppresses Glycolysis and Tumor Progression by Regulating -Mediated Expression in Lung Adenocarcinoma.

作者信息

Wang Li, Wang Huishan, Wu Bining, Zhang Chun, Yu Hualin, Li Xueyan, Wang Qinjue, Shi Xiaoli, Fan Chengfeng, Wang Dayu, Luo Jing, Yang Jinsong

机构信息

Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.

Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Nov 9;13:11459-11470. doi: 10.2147/OTT.S273797. eCollection 2020.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is a leading cause of mortality associated with cancer globally. Thus, it is essential to elucidate its tumorigenesis and prognosis. Accumulating evidence shows that long noncoding RNAs (lncRNAs) play important roles in the occurrence and progression of tumors by regulating their glucose metabolism.

METHODS

Bioinformatics analysis was performed to explore the expression of in LUAD. The level of in LUAD cells and tissues was detected by RT-qPCR. CCK-8, colony formation, EDU and transwell assays were conducted to evaluate the cell growth and migration of LUAD cells (A549 and PC9). High throughput sequencing was used to discover the downstream genes of . The metabolic function of LUAD cells was identified by glucose uptake and lactate production assays. Furthermore, tumor xenografts were established to investigate the effects of on tumor growth in vivo.

RESULTS

Herein, we found that was low-expressed in LUAD, and its level correlated with clinical prognosis. Ectopic expression of inhibited the proliferation and migration of LUAD cells (A549 and PC9). High throughput sequencing and gene enrichment analysis revealed that LINC0551 may be involved in metabolic pathway. Glucose uptake and lactate production assays suggested that suppressed glycolysis of LUAD cells. Mechanistically, our work revealed that inhibited glycolysis in LUAD cells by impairing -mediated transcription of an important glycolysis-related enzyme .

CONCLUSION

In summary, our study identifies as a tumor suppressor in LUAD and implicates the // axis in the glycolytic remodeling of LUAD.

摘要

背景

肺腺癌(LUAD)是全球癌症相关死亡的主要原因。因此,阐明其肿瘤发生和预后至关重要。越来越多的证据表明,长链非编码RNA(lncRNAs)通过调节葡萄糖代谢在肿瘤的发生和发展中发挥重要作用。

方法

进行生物信息学分析以探索lncRNA在LUAD中的表达。通过RT-qPCR检测LUAD细胞和组织中lncRNA的水平。进行CCK-8、集落形成、EDU和transwell实验以评估LUAD细胞(A549和PC9)的细胞生长和迁移。使用高通量测序来发现lncRNA的下游基因。通过葡萄糖摄取和乳酸产生实验确定LUAD细胞的代谢功能。此外,建立肿瘤异种移植模型以研究lncRNA对体内肿瘤生长的影响。

结果

在此,我们发现lncRNA在LUAD中低表达,其水平与临床预后相关。lncRNA的异位表达抑制了LUAD细胞(A549和PC9)的增殖和迁移。高通量测序和基因富集分析表明,LINC0551可能参与代谢途径。葡萄糖摄取和乳酸产生实验表明,lncRNA抑制了LUAD细胞的糖酵解。机制上,我们的研究表明lncRNA通过损害HIF-1α介导的重要糖酵解相关酶PFKFB3的转录来抑制LUAD细胞中的糖酵解。

结论

总之,我们的研究确定lncRNA为LUAD中的肿瘤抑制因子,并表明lncRNA/HIF-1α/PFKFB3轴参与LUAD的糖酵解重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e23/7665500/53f4a73e8c02/OTT-13-11459-g0001.jpg

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