Long non‑coding RNA‑NEF targets glucose transportation to inhibit the proliferation of non‑small‑cell lung cancer cells

Chang,Liang; Xu,Weiling; Zhang,Yan; Gong,Fangchao

doi:10.3892/ol.2019.9919

Long non‑coding RNA‑NEF targets glucose transportation to inhibit the proliferation of non‑small‑cell lung cancer cells

Authors:
- Liang Chang
- Weiling Xu
- Yan Zhang
- Fangchao Gong
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Affiliations: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Radiology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: January 10, 2019 https://doi.org/10.3892/ol.2019.9919
Pages: 2795-2801

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Abstract

Long non‑coding RNA (lncRNA)‑NEF is a newly discovered lncRNA, which exhibits an inhibitory function on the metastasis of hepatocellular carcinoma, while its involvement in other types of malignancy are unknown. In the present study, tumor and adjacent healthy tissues were obtained from patients with non‑small‑cell lung cancer (NSCLC), and blood was obtained from patients with NSCLC and healthy individuals. Expression levels of lncRNA‑NEF in tumor tissue samples, healthy tissue samples and serum were detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Receiver operating characteristic curve analysis and survival curve analysis were performed to evaluate the diagnostic and prognostic value of serum lncRNA‑NEF for NSCLC. The effects of lncRNA‑NEF overexpression in NSCLC cell lines on tumor cell proliferation, glucose uptake, glucose transporter 1 (GLUT1) protein expression and mRNA expression were investigated by Cell Counting kit‑8 assay, glucose uptake assay, western blot analysis and RT‑qPCR, respectively. It was identified that lncRNA‑NEF was downregulated in NSCLC tissues, compared with healthy controls, and the serum level of lncRNA‑NEF was negatively associated with primary tumor stage. Therefore, serum lncRNA‑NEF may be a sensitive diagnostic and prognostic marker for NSCLC. Overexpression of lncRNA‑NEF inhibited NSCLC cell proliferation and glucose uptake, and downregulated GLUT1 expression. Therefore, it can be concluded that lncRNA‑NEF can target glucose transportation to inhibit the proliferation of NSCLC cells.

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1	Gridelli C, Rossi A, Carbone DP, Guarize J, Karachaliou N, Mok T, Petrella F, Spaggiari L and Rosell R: Non-small-cell lung cancer. Nat Rev Dis Primers. 1:150092015. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
3	Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, Ganti AK, et al: Non-small cell lung cancer. J Natl Compr Canc Netw. 8:740–801. 2010. View Article : Google Scholar : PubMed/NCBI
4	Chang JY, Senan S, Paul MA, Mehran RJ, Louie AV, Balter P, Groen HJ, McRae SE, Widder J, Feng L, et al: Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: A pooled analysis of two randomised trials. Lancet Oncol. 16:630–637. 2015. View Article : Google Scholar : PubMed/NCBI
5	Vansteenkiste J, Crinò L, Dooms C, Douillard JY, Faivre-Finn C, Lim E, Rocco G, Senan S, Van Schil P, Veronesi G, et al: 2nd ESMO Consensus Conference on Lung Cancer: Early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up. Ann Oncol. 25:1462–1474. 2014. View Article : Google Scholar : PubMed/NCBI
6	Lalevée S and Feil R: Long noncoding RNAs in human disease: Emerging mechanisms and therapeutic strategies. Epigenomics. 877–879. 2015. View Article : Google Scholar : PubMed/NCBI
7	Bhan A and Mandal SS: Long noncoding RNAs: Emerging stars in gene regulation, epigenetics and human disease. ChemMedChem. 9:1932–1956. 2014. View Article : Google Scholar : PubMed/NCBI
8	Yang YR, Zang SZ, Zhong CL, Li YX, Zhao SS and Feng XJ: Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. Int J Clin Exp Pathol. 7:6929–6935. 2014.PubMed/NCBI
9	Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP and Hou YY: Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 13:4612013. View Article : Google Scholar : PubMed/NCBI
10	Liang WC, Ren JL, Wong CW, Chan SO, Waye MM, Fu WM and Zhang JF: LncRNA-NEF antagonized epithelial to mesenchymal transition and cancer metastasis via cis-regulating FOXA2 and inactivating Wnt/β-catenin signaling. Oncogene. 37:1445–1456. 2018. View Article : Google Scholar : PubMed/NCBI
11	Shaw RJ: Glucose metabolism and cancer. Curr Opin Cell Biol. 18:598–608. 2006. View Article : Google Scholar : PubMed/NCBI
12	Rudlowski C, Becker AJ, Schroder W, Rath W, Büttner R and Moser M: GLUT1 messenger RNA and protein induction relates to the malignant transformation of cervical cancer. Am J Clin Pathol. 120:691–698. 2003. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Yang J, Lin J, Liu T, Chen T, Pan S, Huang W and Li S: Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and their clinical subtypes. Lung Cancer. 85:110–115. 2014. View Article : Google Scholar : PubMed/NCBI
15	Hori SS and Gambhir SS: Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. Sci Transl Med. 3:109ra1162011. View Article : Google Scholar : PubMed/NCBI
16	Xie J, Wu H, Dai C, Pan Q, Ding Z, Hu D, Ji B, Luo Y and Hu X: Beyond Warburg effect-dual metabolic nature of cancer cells. Sci Rep. 4:49272014. View Article : Google Scholar : PubMed/NCBI
17	Zheng J: Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). Oncol Lett. 4:1151–1157. 2012. View Article : Google Scholar : PubMed/NCBI
18	Dang CV, Le A and Gao P: MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res. 15:6479–6483. 2009. View Article : Google Scholar : PubMed/NCBI
19	Alakus H, Batur M, Schmidt M, Drebber U, Baldus SE, Vallböhmer D, Prenzel KL, Metzger R, Bollschweiler E, Hölscher AH and Mönig SP: Variable 18F-fluorodeoxyglucose uptake in gastric cancer is associated with different levels of GLUT-1 expression. Nucl Med Commun. 31:532–538. 2010.PubMed/NCBI
20	Levine AJ and Puzio-Kuter AM: The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 330:1340–1344. 2010. View Article : Google Scholar : PubMed/NCBI
21	Semaan A, Munkarah AR, Arabi H, Bandyopadhyay S, Seward S, Kumar S, Qazi A, Hussein Y, Morris RT and Ali-Fehmi R: Expression of GLUT-1 in epithelial ovarian carcinoma: Correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction. Gynecol Oncol. 121:181–186. 2011. View Article : Google Scholar : PubMed/NCBI
22	Hevia D, Gonzalez-Menendez P, Cepas V and Sainz RM: P 234-Glut 1 overexpression prevents glucose deprivation-induced prostate cancer cell death by increasing pentose phosphate pathway and glutathione. Free Radic Biol Med. 108 Suppl 1:S992017. View Article : Google Scholar