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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

MicroRNA-34c-5p Reduces Malignant Properties of Lung Cancer Cells through Regulation of TBL1XR1/Wnt/β-catenin Signaling

Author(s): Weiqiang Lai, Yonghong Yue and Ganhua Zeng*

Volume 24, Issue 1, 2024

Published on: 27 April, 2023

Page: [114 - 122] Pages: 9

DOI: 10.2174/1566524023666230330083819

Price: $65

Abstract

Introduction: Lung cancer is common cancer with high mortality. A growing number of studies have focused on investigating the regulatory effects of microRNAs (miRs/miRNAs) during cancer progression. Nevertheless, the biological function of miR- 34c-5p in lung cancer and the underlying mechanism have not been determined. This study explored the effect of miR-34c-5p on the malignant behaviors of lung cancer cells.

Methods: In this study, we utilized diverse public databases to obtain differentially expressed miRNAs. Then, qRT-PCR and western blot were conducted to determine miR-34c-5p and transducin β-like 1 X-linked receptor 1 (TBL1XR1) expression. Next, H1299 and H460 cells were transfected with miR-34c-5p-mimic and pcDNA3.1- TBL1XR1. To examine the anticancer effects of miR-34c-5p, CCK-8, scratch, and Matrigel-Transwell assays were conducted to test cell viability, migration, and invasion, respectively. The StarBase database and dual-luciferase reporter gene assay were used to predict and verify the relationship between miR-34c-5p and TBL1XR1.

Results: Finally, Wnt/β-catenin signaling- and epithelial-mesenchymal transition (EMT)- related protein levels were detected using western blot. The results demonstrated that miR-34c-5p was poorly expressed in lung cancer cells, while TBL1XR1 was highly expressed. The findings also confirmed the direct interaction between miR-34c-5p and TBL1XR1. In H1299 and H460 cells, miR-34c-5p overexpression inhibited cell proliferation, migration, and invasion, Wnt/β-catenin signaling activity, and EMT, while TBL1XR1 upregulation reversed these effects of miR-34c-5p overexpression.

Conclusion: These findings illustrated that miR-34c-5p might repress the malignant behaviors of lung cancer cells via TBL1XR1, providing evidence for miR-34c-5p-based lung cancer therapy.

Keywords: Lung cancer, microRNA-34c-5p, proliferation, migration, invasion, TBL1XR1.

« Previous Next »
[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70(1): 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[2]
Wang J, Zou K, Feng X, et al. Downregulation of NMI promotes tumor growth and predicts poor prognosis in human lung adenocarcinomas. Mol Cancer 2017; 16(1): 158.
[http://dx.doi.org/10.1186/s12943-017-0705-9] [PMID: 29025423]
[3]
Kim MJ, Cervantes C, Jung YS, et al. PAF remodels the DREAM complex to bypass cell quiescence and promote lung tumorigenesis. Mol Cell 2021; 81(8): 1698-714.
[http://dx.doi.org/10.1016/j.molcel.2021.02.001]
[4]
Hutvágner G, McLachlan J, Pasquinelli AE, Bálint É, Tuschl T, Zamore PD. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 2001; 293(5531): 834-8.
[http://dx.doi.org/10.1126/science.1062961] [PMID: 11452083]
[5]
Park J, Cho M, Cho J, Kim EE, Song EJ. MicroRNA-101-3p suppresses cancer cell growth by inhibiting the USP47-induced deubiquitination of RPL11. Cancers 2022; 14(4): 964.
[http://dx.doi.org/10.3390/cancers14040964] [PMID: 35205710]
[6]
Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol 2010; 11(4): 252-63.
[http://dx.doi.org/10.1038/nrm2868] [PMID: 20216554]
[7]
Pan Q, Shao Z, Zhang Y, Liu H. MicroRNA-1178-3p suppresses the growth of hepatocellular carcinoma by regulating transducin (beta)-like 1 X-linked receptor 1. Hum Cell 2021; 34(5): 1466-77.
[http://dx.doi.org/10.1007/s13577-021-00565-5] [PMID: 34125401]
[8]
Mastrototaro G, Zaghi M, Massimino L, et al. TBL1XR1 ensures balanced neural development through NCOR complex-mediated regulation of the MAPK pathway. Front Cell Dev Biol 2021; 9: 641410.
[http://dx.doi.org/10.3389/fcell.2021.641410]
[9]
Wang L, Zhao H, Zhang L, Luo H, Chen Q, Zuo X. HSP90AA1, ADRB2, TBL1XR1 and HSPB1 are chronic obstructive pulmonary disease related genes that facilitate squamous cell lung cancer progression. Oncol Lett 2020; 19(3): 2115-22.
[http://dx.doi.org/10.3892/ol.2020.11318] [PMID: 32194709]
[10]
Hiremath IS, Goel A, Warrier S, Kumar AP, Sethi G, Garg M. The multidimensional role of the Wnt/β‐catenin signaling pathway in human malignancies. J Cell Physiol 2022; 237(1): 199-238.
[http://dx.doi.org/10.1002/jcp.30561] [PMID: 34431086]
[11]
Lin JJ, Chin TY, Chen CP, Chan HL, Wu TY. Zika virus: An emerging challenge for obstetrics and gynecology. Taiwan J Obstet Gynecol 2017; 56(5): 585-92.
[http://dx.doi.org/10.1016/j.tjog.2017.08.003] [PMID: 29037541]
[12]
Liu S, Yang N, Wang L, Wei B, Chen J, Gao Y. lncRNA SNHG11 promotes lung cancer cell proliferation and migration via activation of Wnt/β‐catenin signaling pathway. J Cell Physiol 2020; 235(10): 7541-53.
[http://dx.doi.org/10.1002/jcp.29656] [PMID: 32239719]
[13]
Nishi A, Numata S, Tajima A, et al. De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity. Sci Rep 2017; 7(1): 2887.
[http://dx.doi.org/10.1038/s41598-017-02792-z] [PMID: 28588275]
[14]
Liu H, Xu Y, Zhang Q, et al. Prognostic significance of TBL1XR1 in predicting liver metastasis for early stage colorectal cancer. Surg Oncol 2017; 26(1): 13-20.
[http://dx.doi.org/10.1016/j.suronc.2016.12.003] [PMID: 28317580]
[15]
Lin S, Zhen Y, Guan Y, Yi H. Roles of Wnt/beta-catenin signaling pathway regulatory long non-coding RNAs in the pathogenesis of non-small cell lung cancer. Cancer Manag Res 2020; 12: 4181-91.
[16]
Hermeking H. MicroRNAs in the p53 network: Micromanagement of tumour suppression. Nat Rev Cancer 2012; 12(9): 613-26.
[http://dx.doi.org/10.1038/nrc3318] [PMID: 22898542]
[17]
Kasinski AL, Slack FJ. miRNA-34 prevents cancer initiation and progression in a therapeutically resistant K-ras and p53-induced mouse model of lung adenocarcinoma. Cancer Res 2012; 72(21): 5576-87.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-2001] [PMID: 22964582]
[18]
Catuogno S, Cerchia L, Romano G, Pognonec P, Condorelli G, de Franciscis V. miR-34c may protect lung cancer cells from paclitaxel-induced apoptosis. Oncogene 2013; 32(3): 341-51.
[http://dx.doi.org/10.1038/onc.2012.51] [PMID: 22370637]
[19]
Shen Z, Sun S. CircPTCH1 promotes migration in lung cancer by regulating MYCN expression through miR-34c-5p. OncoTargets Ther 2021; 14: 4779-89.
[http://dx.doi.org/10.2147/OTT.S324015]
[20]
Kim NH, Kim HS, Li XY, et al. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition. J Cell Biol 2011; 195(3): 417-33.
[http://dx.doi.org/10.1083/jcb.201103097] [PMID: 22024162]
[21]
Hahn S, Jackstadt R, Siemens H, Hünten S, Hermeking H. SNAIL and miR-34a feed-forward regulation of ZNF281/ZBP99 promotes epithelial-mesenchymal transition. EMBO J 2013; 32(23): 3079-95.
[http://dx.doi.org/10.1038/emboj.2013.236] [PMID: 24185900]
[22]
Xue W, Dahlman JE, Tammela T, et al. Small RNA combination therapy for lung cancer. Proc Natl Acad Sci 2014; 111(34): E3553-61.
[http://dx.doi.org/10.1073/pnas.1412686111] [PMID: 25114235]
[23]
Cao Q, Wang Z, Wang Y, et al. TBL1XR1 promotes migration and invasion in osteosarcoma cells and is negatively regulated by miR-186-5p. Am J Cancer Res 2018; 8(12): 2481-93.
[PMID: 30662805]
[24]
Zhou Q, Wang X, Yu Z, et al. Transducin (β)-like 1 X-linked receptor 1 promotes gastric cancer progression via the ERK1/2 pathway. Oncogene 2017; 36(13): 1873-86.
[http://dx.doi.org/10.1038/onc.2016.352] [PMID: 27694893]
[25]
Zhang T, Liu C, Yu Y, et al. TBL1XR1 is involved in c-Met-mediated tumorigenesis of human nonsmall cell lung cancer. Cancer Gene Ther 2020; 27(3-4): 136-46.
[http://dx.doi.org/10.1038/s41417-019-0111-0] [PMID: 31243347]
[26]
Wang S, Han H, Hu Y, et al. MicroRNA-130a-3p suppresses cell migration and invasion by inhibition of TBL1XR1-mediated EMT in human gastric carcinoma. Mol Carcinog 2018; 57(3): 383-92.
[http://dx.doi.org/10.1002/mc.22762] [PMID: 29091326]
[27]
He X, He L, Hannon GJ. The guardian’s little helper: MicroRNAs in the p53 tumor suppressor network. Cancer Res 2007; 67(23): 11099-101.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2672] [PMID: 18056431]
[28]
Gong L, Song J, Lin X, et al. Serine-arginine protein kinase 1 promotes a cancer stem cell-like phenotype through activation of Wnt/β-catenin signalling in NSCLC. J Pathol 2016; 240(2): 184-96.
[http://dx.doi.org/10.1002/path.4767] [PMID: 27391422]
[29]
Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell 2012; 149(6): 1192-205.
[http://dx.doi.org/10.1016/j.cell.2012.05.012] [PMID: 22682243]
[30]
Smith JL, Jeng S, McWeeney SK, Hirsch AJ. A microRNA screen identifies the WNT signaling pathway as a regulator of the interferon response during flavivirus infection. J Virol 2017; 91(8): e02388-16.
[http://dx.doi.org/10.1128/JVI.02388-16] [PMID: 28148804]
[31]
Vu T, Datta P. Regulation of EMT in colorectal cancer: A culprit in metastasis. Cancers 2017; 9(12): 171.
[http://dx.doi.org/10.3390/cancers9120171] [PMID: 29258163]

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