LncRNA NEAT1 exacerbates non-small cell lung cancer by upregulating EIF4G2 via miR-582-5p sponging

Authors

Keywords:

NEAT1, miR-582-5p, EIF4G2, metastasis, glycolysis

Abstract

Paper description:

  • lncRNA-long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) is involved in the initiation and progression of multiple cancers.
  • We examined the function of NEAT1 in non-small cell lung cancer (NSCLC); cytobiological and biochemical experiments were performed to study its role in an in vivo mouse model.
  • NEAT1 potentiated the malignant potential of NSCLC cells (migration and glycolysis) through the microRNA (miR)-582-5p/eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) subunit axis.
  • The NEAT1/miR-582-5p/EIF4G2 axis could serve as a potential diagnostic or prognostic marker in NSCLC treatment.

Abstract: In this study, we aimed to elucidate the role of long non-coding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the abundance of NEAT1, microRNA-582-5p (miR-582-5p) and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2). Proliferation, apoptosis, metastasis and glycolytic metabolism were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) flow cytometry, transwell assays and fluorescence-based glucose and lactate assay kits. The targets of NEAT1 and miR-582-5p were predicted by the starBase website, and dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify these predictions. Western blot analysis was conducted to detect the protein expression of EIF4G2. A xenograft tumor model was built to clarify the role of NEAT1 in vivo. Results showed that NEAT1 interference inhibited proliferation, metastasis and glycolysis, and facilitated the apoptosis of NSCLC cells. MiR-582-5p was a functional target of NEAT1, and the biological influence of NEAT1 intervention on NSCLC cells was alleviated by transfection with anti-miR-582-5p. MiR-582-5p could bind to EIF4G2 messenger RNA (mRNA); it exerted its antitumor role in NSCLC cells by inhibiting EIF4G2. EIF4G2 was regulated by NEAT1/miR-582-5p signaling. NEAT1 accelerated NSCLC tumor growth via the miR-582-5p/EIF4G2 axis in vivo. In conclusion, NEAT1 affected NSCLC by elevating their malignant potential via the miR-582-5p/EIF4G2 axis.

https://doi.org/10.2298/ABS200218018Z

Received: February 18, 2020; Revised: April 16, 2020; Accepted: April 17, 2020; Published online: April 23, 2020

How to cite this article: Zhang X, Sun Z, Zou Y.LncRNA NEAT1 exacerbates non-small cell lung cancer by upregulating EIF4G2 via miR-582-5p sponging. Arch Biol Sci. 2020;72(2):243-52.

Downloads

Download data is not yet available.

References

Rosell R, Karachaliou N. Lung cancer: Maintenance therapy and precision medicine in NSCLC. Nat Rev Clin Oncol. 2013;10:549-50.

Margaritora S, Cesario A, Cusumano G, Dall'armi V, Porziella V, Meacci E, Lococo F, D'Angelillo R, Congedo MT, Granone P. Pneumonectomy with and without induction chemo-radiotherapy for non-small cell lung cancer: short and long-term results from a single centre. Eur Rev Med Pharmacol Sci. 2013;17:29-40.

Warburg O. On the origin of cancer cells. Science. 1956;123:309-14.

Gill KS, Fernandes P, O'Donovan TR, McKenna SL, Doddakula KK, Power DG, Soden DM, Forde PF. Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response. Biochim Biophys Acta. 2016;1866:87-105.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7-30.

Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155-9.

Wang R, Dong HX, Zeng J, Pan J, Jin XY. LncRNA DGCR5 contributes to CSC-like properties via modulating miR-330-5p/CD44 in NSCLC. J Cell Physiol. 2018;233:7447-56.

Li X, Zhang X, Yang C, Cui S, Shen Q, Xu S. The lncRNA RHPN1-AS1 downregulation promotes gefitinib resistance by targeting miR-299-3p/TNFSF12 pathway in NSCLC. Cell Cycle. 2018;17:1772-83.

Nie W, Ge HJ, Yang XQ, Sun X, Huang H, Tao X, Chen WS, Li B. LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p. Cancer Lett. 2016;371:99-106.

Choudhry H, Albukhari A, Morotti M, Haider S, Moralli D, Smythies J, Schodel J, Green CM, Camps C, Buffa F, Ratcliffe P, Ragoussis J, Harris AL, Mole DR. Tumor hypoxia induces nuclear paraspeckle formation through HIF-2alpha dependent transcriptional activation of NEAT1 leading to cancer cell survival. Oncogene. 2015;34:4482-90.

An J, Lv W, Zhang Y. LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194. Onco Targets Ther. 2017;10:5377-90.

Sun SJ, Lin Q, Ma JX, Shi WW, Yang B, Li F. Long non-coding RNA NEAT1 acts as oncogene in NSCLC by regulating the Wnt signaling pathway. Eur Rev Med Pharmacol Sci. 2017;21:504-10.

Qi L, Liu F, Zhang F, Zhang S, Lv L, Bi Y, Yu Y. lncRNA NEAT1 competes against let-7a to contribute to non-small cell lung cancer proliferation and metastasis. Biomed Pharmacother. 2018;103:1507-15.

Li S, Yang J, Xia Y, Fan Q, Yang KP. Long Noncoding RNA NEAT1 Promotes Proliferation and Invasion via Targeting miR-181a-5p in Non-Small Cell Lung Cancer. Oncol Res. 2018;26:289-96.

O'Connell RM, Rao DS, Baltimore D. microRNA regulation of inflammatory responses. Annu Rev Immunol. 2012;30:295-312.

Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9:839-45.

Bayraktar R, Van Roosbroeck K. miR-155 in cancer drug resistance and as target for miRNA-based therapeutics. Cancer Metastasis Rev. 2018;37:33-44.

Sha HH, Wang DD, Chen D, Liu SW, Wang Z, Yan DL, Dong SC, Feng JF. MiR-138: A promising therapeutic target for cancer. Tumour Biol. 2017;39.

Yong-Ming H, Ai-Jun J, Xiao-Yue X, Jian-Wei L, Chen Y, Ye C. miR-449a: a potential therapeutic agent for cancer. Anticancer Drugs. 2017;28:1067-78.

Wang LL, Zhang M. miR-582-5p is a potential prognostic marker in human non-small cell lung cancer and functions as a tumor suppressor by targeting MAP3K2. Eur Rev Med Pharmacol Sci. 2018;22:7760-7.

Liu J, Liu S, Deng X, Rao J, Huang K, Xu G, Wang X. MicroRNA-582-5p suppresses non-small cell lung cancer cells growth and invasion via downregulating NOTCH1. PLoS One. 2019;14(6):e0217652.

Xie X, Li YS, Xiao WF, Deng ZH, He HB, Liu Q, Luo W. MicroRNA-379 inhibits the proliferation, migration and invasion of human osteosarcoma cells by targetting EIF4G2. Biosci Rep. 2017;37(3):BSR20160542.

Chai Y, Xie M. LINC01579 promotes cell proliferation by acting as a ceRNA of miR-139-5p to upregulate EIF4G2 expression in glioblastoma. J Cell Physiol. 2019;234:23658-66.

Hao GJ, Hao HJ, Ding YH, Wen H, Li XF, Wang QR, Zhang BB. Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells. FEBS Lett. 2017;591:636-45.

Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, Tang W, Cao H. An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget. 2017;8:73271-81.

Han D, Wang J, Cheng G. LncRNA NEAT1 enhances the radio-resistance of cervical cancer via miR-193b-3p/CCND1 axis. Oncotarget. 2018;9:2395-409.

Ding N, Wu H, Tao T, Peng E. NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2. Onco Targets Ther. 2017;10:4905-15.

Li X, Wang X, Song W, Xu H, Huang R, Wang Y, Zhao W, Xiao Z, Yang X. Oncogenic Properties of NEAT1 in Prostate Cancer Cells Depend on the CDC5L-AGRN Transcriptional Regulation Circuit. Cancer Res. 2018;78:4138-49.

Wu F, Mo Q, Wan X, Dan J, Hu H. NEAT1/hsa-mir-98-5p/MAPK6 axis is involved in non-small-cell lung cancer development. J Cell Biochem. 2019;120:2836-46.

Jiang X, Zhou Y, Sun AJ, Xue JL. NEAT1 contributes to breast cancer progression through modulating miR-448 and ZEB1. J Cell Physiol. 2018;233:8558-66.

Zhang M, Weng W, Zhang Q, Wu Y, Ni S, Tan C, Xu M, Sun H, Liu C, Wei P, Du X. The lncRNA NEAT1 activates Wnt/beta-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. J Hematol Oncol. 2018;11:113.

Zhang G, Pian C, Chen Z, Zhang J, Xu M, Zhang L, Chen Y. Identification of cancer-related miRNA-lncRNA biomarkers using a basic miRNA-lncRNA network. PLoS One. 2018;13:e0196681.

Du W, Feng Z, Sun Q. LncRNA LINC00319 accelerates ovarian cancer progression through miR-423-5p/NACC1 pathway. Biochem Biophys Res Commun. 2018;507:198-202.

Luan X, Wang Y. LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a ceRNA against miR-331-3p and miR-338-3p. J Gynecol Oncol. 2018;29:e95.

Zhang Y, Huang W, Ran Y, Xiong Y, Zhong Z, Fan X, Wang Z, Ye Q. miR-582-5p inhibits proliferation of hepatocellular carcinoma by targeting CDK1 and AKT3. Tumour Biol. 2015;36:8309-16.

Zhang X, Zhang Y, Yang J, Li S, Chen J. Upregulation of miR-582-5p inhibits cell proliferation, cell cycle progression and invasion by targeting Rab27a in human colorectal carcinoma. Cancer Gene Ther. 2015;22:475-80.

Jin Y, Tao LP, Yao SC, Huang QK, Chen ZF, Sun YJ, Jin SQ. MicroRNA-582-5p suppressed gastric cancer cell proliferation via targeting AKT3. Eur Rev Med Pharmacol Sci. 2017;21:5112-20.

Gradi A, Imataka H, Svitkin YV, Rom E, Raught B, Morino S, Sonenberg N. A novel functional human eukaryotic translation initiation factor 4G. Mol Cell Biol. 1998;18:334-42.

Caron S, Charon M, Cramer E, Sonenberg N, Dusanter-Fourt I. Selective modification of eukaryotic initiation factor 4F (eIF4F) at the onset of cell differentiation: recruitment of eIF4GII and long-lasting phosphorylation of eIF4E. Mol Cell Biol. 2004;24:4920-8.

Mazan-Mamczarz K, Zhao XF, Dai B, Steinhardt JJ, Peroutka RJ, Berk KL, Landon AL, Sadowska M, Zhang Y, Lehrmann E, Becker KG, Shaknovich R, Liu Z, Gartenhaus RB. Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development. PLoS Genet. 2014;10:e1004105.

Ruggero D, Montanaro L, Ma L, Xu W, Londei P, Cordon-Cardo C, Pandolfi PP. The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat Med. 2004;10:484-6.

Downloads

Published

2020-07-01

How to Cite

1.
Zhang X, Sun Z, Zou Y. LncRNA NEAT1 exacerbates non-small cell lung cancer by upregulating EIF4G2 via miR-582-5p sponging. Arch Biol Sci [Internet]. 2020Jul.1 [cited 2024Mar.29];72(2):243-52. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/5098

Issue

Section

Articles