Downregulated microRNA‑140‑5p expression regulates apoptosis, migration and invasion of lung cancer cells by targeting zinc finger protein 800

Zhuo,Enqing; Cai,Changqing; Liu,Wenzhe; Li,Kunsong; Zhao,Wenzhen

doi:10.3892/ol.2020.12253

Downregulated microRNA‑140‑5p expression regulates apoptosis, migration and invasion of lung cancer cells by targeting zinc finger protein 800

Authors:
- Enqing Zhuo
- Changqing Cai
- Wenzhe Liu
- Kunsong Li
- Wenzhen Zhao
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Affiliations: Department of 2nd Oncology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, P.R. China
Published online on: October 29, 2020 https://doi.org/10.3892/ol.2020.12253
Article Number: 390
Copyright: © Zhuo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Despite advances in the diagnosis and treatment in recent years, lung cancer is still one of the primary causes of cancer‑associated morbidity and mortality in globally. Abnormally expressed microRNAs (miRNAs/miRs) in tumor tissues serve vital roles in the pathological mechanism of tumors and have become prospective biomarkers for cancer diagnosis. The present study aimed to investigate the effects of the miR‑140‑5p/zinc finger protein 800 (ZNF800) axis in lung carcinoma, and determine its potential underlying molecular mechanisms. The degree of cell proliferation was assessed via the MTT assay, while the migratory and invasive abilities of lung cancer cells were determined via the Transwell and Matrigel assays. The expression levels of miR‑140‑5p and ZNF800 were detected via reverse transcription‑quantitative PCR and western blot analyses. The results demonstrated that miR‑140‑5p expression was notably higher in normal human bronchial epithelial cells compared with the respective lung cancer cell lines, H292, PC‑9, CL1‑5 and H460. Furthermore, miR‑140‑5p expression increased in the lung cancer cells compared with the control cells following transfection with miR‑140‑5p mimic. Overexpressing miR‑140‑5p significantly suppressed the proliferative, invasive and migratory abilities of H460 and PC‑9 cells, and stimulated cell apoptosis by upregulating the expression of cleaved‑caspase‑3. Notably, these effects were reversed following transfection with miR‑140‑5p inhibitor. miR‑140‑5p was predicted as a negative regulator of ZNF800, and ZNF800 knockdown significantly suppressed the proliferative and metastatic abilities of lung adenocarcinoma (LUAD) cells, which was comparable to the effects of miR‑140‑5p mimic. Taken together, these results suggest that miR‑140‑5p may block the malignant phenotype of LUAD by negatively regulating ZNF800 expression. Thus, the miR‑140‑5p/ZNF800 axis may be used as an alternative therapeutic target for lung carcinoma in general, and LUAD in particular.

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1	Nanavaty P, Alvarez MS and Alberts WM: Lung cancer screening: advantages, controversies, and applications. Cancer Control. 21:9–14. 2014. View Article : Google Scholar : PubMed/NCBI
2	Olak J and Colson Y: Gender differences in lung cancer: Have we really come a long way, baby? J Thorac Cardiovasc Surg. 128:346–351. 2004. View Article : Google Scholar : PubMed/NCBI
3	Chang YC, Chiou J, Yang YF, Su CY, Lin YF, Yang CN, Lu PJ, Huang MS, Yang CJ and Hsiao M: Therapeutic Targeting of Aldolase A Interactions Inhibits Lung Cancer Metastasis and Prolongs Survival. Cancer Res. 79:4754–4766. 2019.PubMed/NCBI
4	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
5	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
6	Miranda-Filho A, Piñeros M and Bray F: The descriptive epidemiology of lung cancer and tobacco control: A global overview 2018. Salud Publica Mex. 61:219–229. 2019. View Article : Google Scholar : PubMed/NCBI
7	Thawani R, McLane M, Beig N, Ghose S, Prasanna P, Velcheti V and Madabhushi A: Radiomics and radiogenomics in lung cancer: A review for the clinician. Lung Cancer. 115:34–41. 2018. View Article : Google Scholar : PubMed/NCBI
8	Kambayashi Y, Fujimura T, Hidaka T and Aiba S: Biomarkers for predicting efficacies of anti-PD1 antibodies. Front Med (Lausanne). 6:1742019. View Article : Google Scholar : PubMed/NCBI
9	Hjelmborg J, Korhonen T, Holst K, Skytthe A, Pukkala E, Kutschke J, Harris JR, Mucci LA, Christensen K, Czene K, et al Nordic Twin Study of Cancer (NorTwinCan) collaboration, : Lung cancer, genetic predisposition and smoking: The Nordic Twin Study of Cancer. Thorax. 72:1021–1027. 2017. View Article : Google Scholar : PubMed/NCBI
10	Chudgar NP, Bucciarelli PR, Jeffries EM, Rizk NP, Park BJ, Adusumilli PS and Jones DR: Results of the national lung cancer screening trial: Where are we now? Thorac Surg Clin. 25:145–153. 2015. View Article : Google Scholar : PubMed/NCBI
11	Cong L, Zhao Y, Pogue AI and Lukiw WJ: Role of microRNA (miRNA) and viroids in lethal diseases of plants and animals. potential contribution to human neurodegenerative disorders. Biochemistry (Mosc). 83:1018–1029. 2018. View Article : Google Scholar : PubMed/NCBI
12	Bahreini F, Rayzan E and Rezaei N: microRNA-related single-nucleotide polymorphisms and breast cancer. J Cell Physiol. Jul 27–2020.(Epub ahead of print). doi: 10.1002/jcp.29966. View Article : Google Scholar : PubMed/NCBI
13	Tang Y, He R, An J, Deng P, Huang L and Yang W: lncRNA XIST interacts with miR-140 to modulate lung cancer growth by targeting iASPP. Oncol Rep. 38:941–948. 2017. View Article : Google Scholar : PubMed/NCBI
14	Wu M, Wang G, Tian W, Deng Y and Xu Y: MiRNA-based therapeutics for lung cancer. Curr Pharm Des. 23:5989–5996. 2018. View Article : Google Scholar : PubMed/NCBI
15	Zhao JP, Jiang XL, Zhang BY and Su XH: Involvement of microRNA-mediated gene expression regulation in the pathological development of stem canker disease in Populus trichocarpa. PLoS One. 7:e449682012. View Article : Google Scholar : PubMed/NCBI
16	Ling B, Wang GX, Long G, Qiu JH and Hu ZL: Tumor suppressor miR-22 suppresses lung cancer cell progression through post-transcriptional regulation of ErbB3. J Cancer Res Clin Oncol. 138:1355–1361. 2012. View Article : Google Scholar : PubMed/NCBI
17	Turchinovich A, Weiz L, Langheinz A and Burwinkel B: Characterization of extracellular circulating microRNA. Nucleic Acids Res. 39:7223–7233. 2011. View Article : Google Scholar : PubMed/NCBI
18	Kropp J, Salih SM and Khatib H: Expression of microRNAs in bovine and human pre-implantation embryo culture media. Front Genet. 5:912014. View Article : Google Scholar : PubMed/NCBI
19	Wang X, Wang T, Chen C, Wu Z, Bai P, Li S, Chen B, Liu R, Zhang K, Li W, et al: Serum exosomal miR-210 as a potential biomarker for clear cell renal cell carcinoma. J Cell Biochem. Oct 10–2018.(Epub ahead of print). doi: 1002/jcb.27347.
20	Yang F, Ning Z, Ma L, Liu W, Shao C, Shu Y and Shen H: Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts. Mol Cancer. 16:1482017. View Article : Google Scholar : PubMed/NCBI
21	Sueta A, Yamamoto Y, Tomiguchi M, Takeshita T, Yamamoto-Ibusuki M and Iwase H: Differential expression of exosomal miRNAs between breast cancer patients with and without recurrence. Oncotarget. 8:69934–69944. 2017. View Article : Google Scholar : PubMed/NCBI
22	Dong F, Xu T, Shen Y, Zhong S, Chen S, Ding Q and Shen Z: Dysregulation of miRNAs in bladder cancer: Altered expression with aberrant biogenesis procedure. Oncotarget. 8:27547–27568. 2017. View Article : Google Scholar : PubMed/NCBI
23	Liu L, Lai X, Yuan C, Lv X, Yu T, He W, Liu J and Zhang H: Aberrant expression of miR-153 is associated with the poor prognosis of cervical cancer. Oncol Lett. 15:9183–9187. 2018.PubMed/NCBI
24	Zhang W, Zou C, Pan L, Xu Y, Qi W, Ma G, Hou Y and Jiang P: MicroRNA-140-5p inhibits the progression of colorectal cancer by targeting VEGFA. Cell Physiol Biochem. 37:1123–1133. 2015. View Article : Google Scholar : PubMed/NCBI
25	Hu Y, Li Y, Wu C, Zhou L, Han X, Wang Q, Xie X, Zhou Y and Du Z: MicroRNA-140-5p inhibits cell proliferation and invasion by regulating VEGFA/MMP2 signaling in glioma. Tumour Biol. 39:10104283176975582017. View Article : Google Scholar : PubMed/NCBI
26	Li W and He F: Monocyte to macrophage differentiation-associated (MMD) targeted by miR-140-5p regulates tumor growth in non-small cell lung cancer. Biochem Biophys Res Commun. 450:844–850. 2014. View Article : Google Scholar : PubMed/NCBI
27	Yang P, Xiong J, Zuo L, Liu K and Zhang H: miR 140 5p regulates cell migration and invasion of non small cell lung cancer cells through targeting VEGFA. Mol Med Rep. 18:2866–2872. 2018.PubMed/NCBI
28	Jing P, Sa N, Liu X, Liu X and Xu W: MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma. Exp Mol Pathol. 100:132–138. 2016. View Article : Google Scholar : PubMed/NCBI
29	Lu Y, Qin T, Li J, Wang L, Zhang Q, Jiang Z and Mao J: MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer. Cancer Gene Ther. 24:386–392. 2017. View Article : Google Scholar : PubMed/NCBI
30	Cha Y, He Y, Ouyang K, Xiong H, Li J and Yuan X: MicroRNA-140-5p suppresses cell proliferation and invasion in gastric cancer by targeting WNT1 in the WNT/β-catenin signaling pathway. Oncol Lett. 16:6369–6376. 2018.PubMed/NCBI
31	Fang Z, Yin S, Sun R, Zhang S, Fu M, Wu Y, Zhang T, Khaliq J and Li Y: miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1. Mol Cancer. 16:1392017. View Article : Google Scholar : PubMed/NCBI
32	He Y, Deng F, Zhao S, Zhong S, Zhao J, Wang D, Chen X, Zhang J, Hou J, Zhang W, et al: Analysis of miRNA-mRNA network reveals miR-140-5p as a suppressor of breast cancer glycolysis via targeting GLUT1. Epigenomics. 11:1021–1036. 2019. View Article : Google Scholar : PubMed/NCBI
33	Chang QQ, Chen CY, Chen Z and Chang S: LncRNA PVT1 promotes proliferation and invasion through enhancing Smad3 expression by sponging miR-140-5p in cervical cancer. Radiol Oncol. 53:443–452. 2019. View Article : Google Scholar : PubMed/NCBI
34	Cunningham F, Achuthan P, Akanni W, Allen J, Amode MR, Armean IM, Bennett R, Bhai J, Billis K, Boddu S, et al: Ensembl 2019. Nucleic Acids Res. 47:D745–D751. 2019. View Article : Google Scholar : PubMed/NCBI
35	Zhang Y, Xu R, Li G, Xie X, Long J and Wang H: Loss of expression of the differentially expressed in adenocarcinoma of the lung (DAL-1) protein is associated with metastasis of non-small cell lung carcinoma cells. Tumour Biol. 33:1915–1925. 2012. View Article : Google Scholar : PubMed/NCBI
36	Sano Y, Hashimoto E, Nakatani N, Abe M, Satoh Y, Sakata K, Fujii T, Fujimoto-Ouchi K, Sugimoto M, Nagahashi S, et al: Combining onartuzumab with erlotinib inhibits growth of non-small cell lung cancer with activating EGFR mutations and HGF overexpression. Mol Cancer Ther. 14:533–541. 2015. View Article : Google Scholar : PubMed/NCBI
37	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
38	Crone M, Hallman K, Lloyd V, Szmyd M, Badamo B, Morse M and Dinda S: The antiestrogenic effects of black cohosh on BRCA1 and steroid receptors in breast cancer cells. Breast Cancer (Dove Med Press). 11:99–110. 2019.PubMed/NCBI
39	Lee YS and Dutta A: MicroRNAs in cancer. Annu Rev Pathol. 4:199–227. 2009. View Article : Google Scholar : PubMed/NCBI
40	Billeter AT, Barnett RE, Druen D, Polk HC Jr and van Berkel VH: MicroRNA as a new factor in lung and esophageal cancer. Semin Thorac Cardiovasc Surg. 24:155–165. 2012. View Article : Google Scholar : PubMed/NCBI
41	Tong X, Su P, Yang H, Chi F, Shen L, Feng X, Jiang H, Zhang X and Wang Z: MicroRNA-598 inhibits the proliferation and invasion of non-small cell lung cancer cells by directly targeting ZEB2. Exp Ther Med. 16:5417–5423. 2018.PubMed/NCBI
42	Lamichhane SR, Thachil T, De Ieso P, Gee H, Moss SA and Milic N: Prognostic role of MicroRNAs in human non-small-cell lung cancer: A systematic review and meta-analysis. Dis Markers. 2018:83090152018. View Article : Google Scholar : PubMed/NCBI
43	Jeong HC, Kim EK, Lee JH, Lee JM, Yoo HN and Kim JK: Aberrant expression of let-7a miRNA in the blood of non-small cell lung cancer patients. Mol Med Rep. 4:383–387. 2011.PubMed/NCBI
44	Jia Z, Zhang Y, Xu Q, Guo W and Guo A: miR-126 suppresses epithelial-to-mesenchymal transition and metastasis by targeting PI3K/AKT/Snail signaling of lung cancer cells. Oncol Lett. 15:7369–7375. 2018.PubMed/NCBI
45	Huang H, Wang Y, Li Q, Fei X, Ma H and Hu R: miR-140-3p functions as a tumor suppressor in squamous cell lung cancer by regulating BRD9. Cancer Lett. 446:81–89. 2019. View Article : Google Scholar : PubMed/NCBI
46	Flamini V, Dudley E, Jiang WG and Cui Y: Distinct mechanisms by which two forms of miR-140 suppress the malignant properties of lung cancer cells. Oncotarget. 9:36474–36491. 2018. View Article : Google Scholar : PubMed/NCBI