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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

LncRNA NBR2 Regulates Cancer Cell Stemness and Predicts Survival in Non-small Cell Cancer Patients by Downregulating TGF-β1

Author(s): Jun Huang, Qiuhua Yu, Junjie Zhang, Wenbin lu, Qian Liu, Ying Chu, Yanjuan Zhou, Renshu Tu, Huxiang Zhou and Qiang Wang*

Volume 24, Issue 8, 2023

Published on: 10 October, 2022

Page: [1059 - 1069] Pages: 11

DOI: 10.2174/1389201023666220728143410

Price: $65

Abstract

Background: LncRNA NBR2 is a key regulator in cancer metabolism. However, its role in lung cancer is unknown.

Objective: This study aimed to explore the function of NBR2 in non-small cell lung cancer (NSCLC), which is the most common type of lung cancer.

Methods: Paired NSCLC and non-cancer tissues were collected from 68 patients with NSCLC. The expression of NBR2 and transforming growth factor-β1 (TGF-β1) in these samples was analyzed by RT-qPCR. The prognostic value of NBR2 for NSCLC was explored by performing a 5-year follow-up study. The interaction between NBR2 and TGF-β1 in two NSCLC cell lines was detected by overexpression assay, followed by RT-qPCR and Western blot analysis. Flow cytometry was performed to evaluate the role of NBR2 and TGF-β1 in regulating NSCLC cell stemness.

Results: NBR2 was significantly downregulated in NSCLC tissues than that in non-cancer tissues of NSCLC patients, and low expression levels of NBR2 predicted poor survival. TGF-β1 was significantly upregulated in NSCLC tissues than that in non-cancer tissues, and was inversely correlated with NBR2. Overexpression of NBR2 downregulated TGF-β1, while overexpression of TGF-β1 did not affect the expression of NBR2. Overexpression of NBR2 inhibited, while overexpression of TGF-β1 promoted NSCLC cell stemness. Overexpression of TGF-β1 attenuated the effects of overexpression of NBR2. Mechanically, NBR2 interacted with Notch1 protein to inhibit its expression, thereby inhibiting the expression of TGF-β1 and further affecting the proportion of CD133+ cells.

Conclusion: LncRNA NBR2 regulates cancer cell stemness and predicts survival in NSCLC possibly by downregulating TGF-β1 through Notch1.

Keywords: non-small cell lung cancer, lncRNA NBR2, TGF-β1, stemness

« Previous Next »
[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer Statistics, 2017. CA Cancer J. Clin., 2017, 67(1), 7-30.
[http://dx.doi.org/10.3322/caac.21387] [PMID: 28055103]
[2]
Novello, S.; Barlesi, F.; Califano, R.; Cufer, T.; Ekman, S.; Levra, M.G.; Kerr, K.; Popat, S.; Reck, M.; Senan, S.; Simo, G.V.; Vansteenkiste, J.; Peters, S. Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2016, 27(Suppl. 5), v1-v27.
[http://dx.doi.org/10.1093/annonc/mdw326] [PMID: 27664245]
[3]
Thomson, C.S.; Forman, D. Cancer survival in England and the influence of early diagnosis: What can we learn from recent EUROCARE results? Br. J. Cancer, 2009, 101(Suppl. 2), S102-S109.
[http://dx.doi.org/10.1038/sj.bjc.6605399]
[4]
Torre, L.A.; Siegel, R.L.; Jemal, A. Lung cancer statistics. In: Lung Cancer and Personalized Medicine; Springer: Cham,, 2016; 893, pp. 1-19.
[http://dx.doi.org/10.1007/978-3-319-24223-1_1]
[5]
Fan, H.; Shao, Z.Y.; Xiao, Y.Y. Incidence and survival of non-small cell lung cancer in Shanghai: A population-based cohort study. BMJ Open, 2015, 5(12), e009419.
[http://dx.doi.org/10.1136/bmjopen-2015-009419]
[6]
Sekido, Y.; Fong, K.M.; Minna, J.D. Molecular genetics of lung cancer. Annu. Rev. Med., 2003, 54, 73-87.
[http://dx.doi.org/10.1146/annurev.med.54.101601.152202] [PMID: 12471176]
[7]
Steliga, M.A.; Dresler, C.M. Epidemiology of lung cancer: Smoking, secondhand smoke, and genetics. Surg. Oncol. Clin. N. Am., 2011, 20(4), 605-618.
[http://dx.doi.org/10.1016/j.soc.2011.07.003] [PMID: 21986260]
[8]
Gutschner, T.; Diederichs, S. The hallmarks of cancer: A long non-coding RNA point of view. RNA Biol., 2012, 9(6), 703-719.
[http://dx.doi.org/10.4161/rna.20481]
[9]
Spizzo, R.; Almeida, M.I. Colombatti, A Long non-coding RNAs and cancer: A new frontier of translational research? Oncogene, 2012, 31(43), 4577-4587.
[http://dx.doi.org/10.1038/onc.2011.621]
[10]
Schmitt, A.M.; Chang, H.Y. Long noncoding rnas in cancer pathways. Cancer Cell, 2016, 29(4), 452-463.
[http://dx.doi.org/10.1016/j.ccell.2016.03.010]
[11]
Qi, P.; Du, X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod. Pathol., 2013, 26(2), 155-165.
[http://dx.doi.org/10.1038/modpathol.2012.160] [PMID: 22996375]
[12]
Liu, X.; Xiao, Z.D.; Han, L. LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. Nat. Cell Biol., 2016, 18(4), 431-442.
[http://dx.doi.org/10.1038/ncb3328]
[13]
Zheng, J. Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation. Oncol. Lett., 2012, 4(6), 1151-1157.
[http://dx.doi.org/10.3892/ol.2012.928]
[14]
Liu, X.; Gan, B. lncRNA NBR2 modulates cancer cell sensitivity to phenformin through GLUT1. Cell Cycle, 15(24), 3471-3481.
[http://dx.doi.org/10.1080/15384101.2016.1249545]
[15]
Papageorgis, P. TGFbeta signaling in tumor initiation, epithelial-to-mesenchymal transition, and metastasis. J. Oncol., 2015, 2015, 587193.
[http://dx.doi.org/10.1155/2015/587193]
[16]
Cai, W.; Wu, B.; Li, Z.; He, P.; Wang, B.; Cai, A.; Zhang, X. LncRNA NBR2 inhibits epithelial-mesenchymal transition by regulating Notch1 signaling in osteosarcoma cells. J. Cell. Biochem., 2018.
[http://dx.doi.org/10.1002/jcb.27508] [PMID: 30187965]
[17]
Yang, Z.; Qi, Y.; Lai, N. Notch1 signaling in melanoma cells promoted tumor-induced immunosuppression via upregulation of TGF-β1. J. Exp. Clin. Cancer Res., 2018, 37(1), 1.
[http://dx.doi.org/10.1186/s13046-017-0664-4]
[18]
Neuzillet, C.; Tijeras-Raballand, A.; Cohen, R.; Cros, J.; Faivre, S.; Raymond, E.; de Gramont, A. Targeting the TGFβ pathway for cancer therapy. Pharmacol. Ther., 2015, 147, 22-31.
[http://dx.doi.org/10.1016/j.pharmthera.2014.11.001] [PMID: 25444759]
[19]
Bruna, A.; Greenwood, W.; Le Quesne, J.; Teschendorff, A.; Miranda-Saavedra, D.; Rueda, O.M.; Sandoval, J.L.; Vidakovic, A.T.; Saadi, A.; Pharoah, P.; Stingl, J.; Caldas, C. TGFβ induces the formation of tumour-initiating cells in claudinlow breast cancer. Nat. Commun., 2012, 3, 1055.
[http://dx.doi.org/10.1038/ncomms2039] [PMID: 22968701]
[20]
Hasegawa, T.; Yashiro, M.; Nishii, T.; Matsuoka, J.; Fuyuhiro, Y.; Morisaki, T.; Fukuoka, T.; Shimizu, K.; Shimizu, T.; Miwa, A.; Hirakawa, K. Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-β signaling. Int. J. Cancer, 2014, 134(8), 1785-1795.
[http://dx.doi.org/10.1002/ijc.28520] [PMID: 24155219]
[21]
Wu, W.; Chen, F.; Cui, X.; Yang, L.; Chen, J.; Zhao, J.; Huang, D.; Liu, J.; Yang, L.; Zeng, J.; Zeng, Z.; Pan, Y.; Su, F.; Cai, J.; Ying, Z.; Zhao, Q.; Song, E.; Su, S. LncRNA NKILA suppresses TGF-β-induced epithelial-mesenchymal transition by blocking NF-κB signaling in breast cancer. Int. J. Cancer, 2018, 143(9), 2213-2224.
[http://dx.doi.org/10.1002/ijc.31605] [PMID: 29761481]

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