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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Regulatory Mechanism of lncRNA CTBP1-AS2 in Nasopharyngeal Carcinoma Cell Proliferation and Apoptosis via the miR-140-5p/BMP2 Axis

Author(s): Bo Huang, Yiliang Li, Zhuoxia Deng, Guiping Lan, Yongfeng Si* and Qiao Zhou

Volume 29, Issue 7, 2022

Published on: 23 August, 2022

Page: [621 - 630] Pages: 10

DOI: 10.2174/0929866529666220726151339

Price: $65

Abstract

Objective: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma. LncRNA CTBP1-AS2 (CTBP1-AS2) has effects on tumor cell growth. This study explored the mechanism of CTBP1-AS2 on NPC cells.

Methods: CTBP1-AS2 expressions in immortalized nasopharyngeal epithelial (NP69) and 6 human NPC cells were detected by RT-qPCR and SUNE-1/CNE-1 cells with relative high/low expressions were selected. Cell proliferation and apoptosis were detected by CCK-8, colony formation assays, and flow cytometry. The binding sites between CTBP1-AS2 and miR-140-5p and miR-140-5p and BMP2 were predicted, and the binding relationships were verified by dual-luciferase assay. BMP2 level was detected by Western blot. miR-140-5p was silenced, or BMP2 was overexpressed in SUNE-1 cells with si-CTBP1-AS2 to study the effects of miR-140-5p and BMP2 on CTBP1-AS2 silencing-inhibited malignant behaviors.

Results: CTBP1-AS2 was upregulated in NPC cells. CTBP1-AS2 silencing suppressed NPC cell proliferation and promoted apoptosis. CTBP1-AS2 silencing in SUNE-1 cells raised miR-140-5p expression and repressed BMP2 level. CTBP1-AS2 overexpression in CNE-1 cells suppressed miR- 140-5p expression and elevated BMP2 levels.

Discussion: In mechanism, miR-140-5p overexpression decreased BMP2 levels, reduced NPC cell proliferation, and promoted apoptosis. miR-140-5p knockdown or BMP2 overexpression enhanced NPC cell proliferation and inhibited apoptosis, thus restoring NPC cell malignant behaviors inhibited by silencing CTBP1-AS2.

Conclusion: CTBP1-AS2 decreased miR-140-5p-induced BMP2 inhibition via functioning as a ceRNA of miR-140-5p and promoted BMP2 expression, thereby promoting NPC cell proliferation and suppressing apoptosis.

Keywords: Nasopharyngeal carcinoma, LncRNA CTBP1-AS2, miR-140-5p, BMP2, proliferation, apoptosis, immortalized nasopharyngeal epithelial cells, ceRNA, subcellular localization.

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[1]
Guo, R.; Mao, Y.P.; Tang, L.L.; Chen, L.; Sun, Y.; Ma, J. The evolution of nasopharyngeal carcinoma staging. Br. J. Radiol., 2019, 92(1102), 20190244.
[http://dx.doi.org/10.1259/bjr.20190244] [PMID: 31298937]
[2]
Kamran, S.C.; Riaz, N.; Lee, N. Nasopharyngeal carcinoma. Surg. Oncol. Clin. N. Am., 2015, 24(3), 547-561.
[http://dx.doi.org/10.1016/j.soc.2015.03.008] [PMID: 25979399]
[3]
Chen, Y.P.; Chan, A.T.C.; Le, Q.T.; Blanchard, P.; Sun, Y.; Ma, J. Nasopharyngeal carcinoma. Lancet, 2019, 394(10192), 64-80.
[http://dx.doi.org/10.1016/S0140-6736(19)30956-0] [PMID: 31178151]
[4]
Lee, H.M.; Okuda, K.S.; González, F.E.; Patel, V. Current perspectives on nasopharyngeal carcinoma. Adv. Exp. Med. Biol., 2019, 1164, 11-34.
[http://dx.doi.org/10.1007/978-3-030-22254-3_2] [PMID: 31576537]
[5]
Zhou, H.; Gao, Z.; Wan, F. Taurine-upregulated gene 1 contributes to cancers through sponging microRNA. Acta Biochim. Biophys. Sin. (Shanghai), 2019, 51(2), 123-130.
[http://dx.doi.org/10.1093/abbs/gmy156] [PMID: 30590378]
[6]
Peng, W.X.; Koirala, P.; Mo, Y.Y. LncRNA-mediated regulation of cell signaling in cancer. Oncogene, 2017, 36(41), 5661-5667.
[http://dx.doi.org/10.1038/onc.2017.184] [PMID: 28604750]
[7]
Li, Q.; Yue, W.; Li, M.; Jiang, Z.; Hou, Z.; Liu, W.; Ma, N.; Gan, W.; Li, Y.; Zhou, T.; Yue, W.; Chen, S. Downregulating long non-coding RNAs CTBP1-AS2 inhibits colorectal cancer development by modulating the miR-93-5p/TGF-β/SMAD2/3 pathway. Front. Oncol., 2021, 11, 626620.
[http://dx.doi.org/10.3389/fonc.2021.626620] [PMID: 33937030]
[8]
Zhang, X.; Wang, D.; Liu, B.; Jin, X.; Wang, X.; Pan, J.; Tu, W.; Shao, Y. IMP3 accelerates the progression of prostate cancer through inhibiting PTEN expression in a SMURF1-dependent way. J. Exp. Clin. Cancer Res., 2020, 39(1), 190.
[http://dx.doi.org/10.1186/s13046-020-01657-0] [PMID: 32938489]
[9]
Yang, S.; Shi, F.; Du, Y.; Wang, Z.; Feng, Y.; Song, J.; Liu, Y.; Xiao, M. Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163. Cancer Cell Int., 2020, 20(1), 343.
[http://dx.doi.org/10.1186/s12935-020-01430-5] [PMID: 32742190]
[10]
Lan, B.; Ge, J.W.; Cheng, S.W.; Zheng, X.L.; Liao, J.; He, C.; Rao, Z.Q.; Wang, G.Z. Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats. J. Integr. Med., 2020, 18(4), 344-350.
[http://dx.doi.org/10.1016/j.joim.2020.01.008] [PMID: 32107172]
[11]
Nie, X.; Fan, J.; Li, H.; Yin, Z.; Zhao, Y.; Dai, B.; Dong, N.; Chen, C.; Wang, D.W. miR-217 promotes cardiac hypertrophy and dysfunction by targeting PTEN. Mol. Ther. Nucleic Acids, 2018, 12, 254-266.
[http://dx.doi.org/10.1016/j.omtn.2018.05.013] [PMID: 30195764]
[12]
Abdollahzadeh, R.; Daraei, A.; Mansoori, Y.; Sepahvand, M.; Amoli, M.M.; Tavakkoly-Bazzaz, J. Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer. J. Cell. Physiol., 2019, 234(7), 10080-10100.
[http://dx.doi.org/10.1002/jcp.27941] [PMID: 30537129]
[13]
Markopoulos, G.S.; Roupakia, E.; Tokamani, M.; Chavdoula, E.; Hatziapostolou, M.; Polytarchou, C.; Marcu, K.B.; Papavassiliou, A.G.; Sandaltzopoulos, R.; Kolettas, E. A step-by-step microRNA guide to cancer development and metastasis. Cell Oncol. (Dordr.), 2017, 40(4), 303-339.
[http://dx.doi.org/10.1007/s13402-017-0341-9] [PMID: 28748501]
[14]
Zhu, M.; Zhang, C.; Chen, D.; Chen, S.; Zheng, H. lncRNA MALAT1 potentiates the progression of tongue squamous cell carcinoma through regulating miR-140-5p-PAK1 pathway. OncoTargets Ther., 2019, 12, 1365-1377.
[http://dx.doi.org/10.2147/OTT.S192069] [PMID: 30863103]
[15]
Fang, Z.; Yin, S.; Sun, R.; Zhang, S.; Fu, M.; Wu, Y.; Zhang, T.; Khaliq, J.; Li, Y. miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1. Mol. Cancer, 2017, 16(1), 139.
[http://dx.doi.org/10.1186/s12943-017-0708-6] [PMID: 28818100]
[16]
Yan, X.; Zhu, Z.; Xu, S.; Yang, L.N.; Liao, X.H.; Zheng, M.; Yang, D.; Wang, J.; Chen, D.; Wang, L.; Liu, X.; Liu, J.; Chen, R.H.; Zhou, X.Z.; Lu, K.P.; Liu, H. MicroRNA-140-5p inhibits hepatocellular carcinoma by directly targeting the unique isomerase Pin 1 to block multiple cancer-driving pathways. Sci. Rep., 2017, 7(1), 45915.
[http://dx.doi.org/10.1038/srep45915] [PMID: 28383568]
[17]
Chen, C.; Zou, L.X.; Lin, Q.Y.; Yan, X.; Bi, H.L.; Xie, X.; Wang, S.; Wang, Q.S.; Zhang, Y.L.; Li, H.H. Resveratrol as a new inhibitor of immunoproteasome prevents PTEN degradation and attenuates cardiac hypertrophy after pressure overload. Redox Biol., 2019, 20, 390-401.
[http://dx.doi.org/10.1016/j.redox.2018.10.021] [PMID: 30412827]
[18]
Dai, Y.; Zhang, X.; Xing, H.; Zhang, Y.; Cao, H.; Sang, J.; Gao, L.; Wang, L. Downregulated long non-coding RNA SNHG7 restricts proliferation and boosts apoptosis of nasopharyngeal carcinoma cells by elevating microRNA-140-5p to suppress GLI3 expression. Cell Cycle, 2020, 19(4), 448-463.
[http://dx.doi.org/10.1080/15384101.2020.1712033] [PMID: 31944163]
[19]
Wang, M.H.; Zhou, X.M.; Zhang, M.Y.; Shi, L.; Xiao, R.W.; Zeng, L.S.; Yang, X.Z.; Zheng, X.F.S.; Wang, H.Y.; Mai, S.J. BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway. Aging (Albany NY), 2017, 9(4), 1326-1340.
[http://dx.doi.org/10.18632/aging.101230] [PMID: 28455969]
[20]
Xiao, B.; Zhang, W.; Kuang, Z.; Lu, J.; Li, W.; Deng, C.; He, Y.; Lei, T.; Hao, W.; Sun, Z.; Li, L. SOX9 promotes nasopharyngeal carcinoma cell proliferation, migration and invasion through BMP2 and mTOR signaling. Gene, 2019, 715, 144017.
[http://dx.doi.org/10.1016/j.gene.2019.144017] [PMID: 31357026]
[21]
Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res., 2014, 42(Database issue), D92-D97.
[http://dx.doi.org/10.1093/nar/gkt1248] [PMID: 24297251]
[22]
Yang, M.; Huang, W. Circular RNAs in nasopharyngeal carcinoma. Clin. Chim. Acta, 2020, 508, 240-248.
[http://dx.doi.org/10.1016/j.cca.2020.05.029] [PMID: 32417214]
[23]
Cui, K.; Zhu, G. LncRNA CTBP1-AS2 regulates miR-216a/PTEN to suppress ovarian cancer cell proliferation. J. Ovarian Res., 2020, 13(1), 84.
[http://dx.doi.org/10.1186/s13048-020-00689-6] [PMID: 32711584]
[24]
Yang, Y.; Gao, M.; Li, Y.; Li, M.; Ma, Q. LncRNA CTBP1-AS2 facilitates gastric cancer progression via regulating the miR-139-3p/MMP11 axis. OncoTargets Ther., 2020, 13, 11537-11547.
[http://dx.doi.org/10.2147/OTT.S264394] [PMID: 33204108]
[25]
Bruce, J.P.; Liu, F.F. MicroRNAs in nasopharyngeal carcinoma. Chin. J. Cancer, 2014, 33(11), 539-544.
[http://dx.doi.org/10.5732/cjc.014.10175] [PMID: 25367334]
[26]
Liu, L.X.; Liu, B.; Yu, J.; Zhang, D.Y.; Shi, J.H.; Liang, P. SP1-induced upregulation of lncRNA CTBP1-AS2 accelerates the hepatocellular carcinoma tumorigenesis through targeting CEP55 via sponging miR-195-5p. Biochem. Biophys. Res. Commun., 2020, 533(4), 779-785.
[http://dx.doi.org/10.1016/j.bbrc.2020.09.080] [PMID: 32988587]

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