miR‑491‑5p inhibits the proliferation and migration of A549 cells by FOXP4

Wu,Fuyong; Ji,Aiping; Zhang,Zhenkun; Li,Jinfang; Li,Penglong

doi:10.3892/etm.2021.10054

miR‑491‑5p inhibits the proliferation and migration of A549 cells by FOXP4

Authors:
- Fuyong Wu
- Aiping Ji
- Zhenkun Zhang
- Jinfang Li
- Penglong Li
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Affiliations: Third Department of Oncology, People's Hospital of Shouguang, Shouguang, Shandong 262700, P.R. China, Second Department of Oncology, People's Hospital of Shouguang, Shouguang, Shandong 262700, P.R. China, Department of Oncology, Yantai Laiyang Central Hospital, Laiyang, Shandong 265200, P.R. China
Published online on: April 14, 2021 https://doi.org/10.3892/etm.2021.10054
Article Number: 622
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aberrant expression of microRNAs (miRNAs/miRs) plays a key role in the development of non‑small cell lung cancer (NSCLC). In the present study, lower miRNA (miR)‑491‑5p levels and a higher forkhead box P4 (FOXP4) mRNA level were observed in NSCLC tissues and cell lines, compared to adjacent tissues and the normal human lung epithelial cell line BEAS‑2B, respectively. A549 cell proliferation and migration were inhibited upon transfection of miR‑491‑5p mimics compared to miR‑negative control (NC) mimics. In addition, compared to miR‑NC mimics, overexpression of miR‑491‑5p decreased FOXP4 expression, while downregulation of miR‑491‑5p increased FOXP4 expression in A549 cells. The dual luciferase assay confirmed that the 3'untranslated region of FOXP4 was a target for miR‑491‑5p in A549 cells. Moreover, compared with the control short hairpin (sh)RNA, there was lower expression levels of TGF‑β and its downstream targets (MMP‑2 and MMP‑9) in the FOXP4 shRNA group. Similarly, compared to miR‑NC mimics, overexpression of miR‑491‑5p decreased MMP‑2 and MMP‑9 expression levels. In FOXP4‑knockdown A549 cells, overexpression of miR‑491‑5p showed little effect on cell proliferation/migration. In A549 cells, overexpression of FOXP4 partially reversed the miR‑491‑5p mimics‑induced inhibition on the cell proliferation and migration. These results may provide new insights into the role of miR‑491‑5p in NSCLC.

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1	Torre LA, Sauer AM, Chen MS Jr, Kagawa-Singer M, Jemal A and Siegel RL: Cancer statistics for Asian Americans, Native Hawaiians, and Pacific Islanders, 2016: Converging incidence in males and females. CA Cancer J Clin. 66:182–202. 2016.PubMed/NCBI View Article : Google Scholar
2	Chen Z, Fillmore CM, Hammerman PS, Kim CF and Wong KK: Non-small-cell lung cancers: A heterogeneous set of diseases. Nat Rev Cancer. 14:535–546. 2014.PubMed/NCBI View Article : Google Scholar
3	Wood SL, Pernemalm M, Crosbie PA and Whetton AD: The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev. 40:558–566. 2014.PubMed/NCBI View Article : Google Scholar
4	Laskin JJ and Sandler AB: State of the art in therapy for non-small cell lung cancer. Cancer Invest. 23:427–442. 2005.PubMed/NCBI View Article : Google Scholar
5	Lagos-Quintana M, Rauhut R, Lendeckel W and Tuschl T: Identification of novel genes coding for small expressed RNAs. Science. 294:853–858. 2001.PubMed/NCBI View Article : Google Scholar
6	Paliouras AR, Monteverde T and Garofalo M: Oncogene-induced regulation of microRNA expression: Implications for cancer initiation, progression and therapy. Cancer Lett. 421:152–160. 2018.PubMed/NCBI View Article : Google Scholar
7	Ye MF, Zhang JG, Guo TX and Pan XJ: MiR-504 inhibits cell proliferation and invasion by targeting LOXL2 in non small cell lung cancer. Biomed Pharmacother. 97:1289–1295. 2018.PubMed/NCBI View Article : Google Scholar
8	Hao J, Zhao S, Zhang Y, Zhao Z, Ye R, Wen J and Li J: Emerging role of microRNAs in cancer and cancer stem cells. J Cell Biochem. 115:605–610. 2014.PubMed/NCBI View Article : Google Scholar
9	Zhou Q, Huang SX, Zhang F, Li SJ, Liu C, Xi YY, Wang L, Wang X, He QQ, Sun CC and Li DJ: MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non-small cell lung cancer. Cell Prolif. 50(e12394)2017.PubMed/NCBI View Article : Google Scholar
10	Xiong K, Shao LH, Zhang HQ, Jin L, Wei W, Dong Z, Zhu YQ, Wu N, Jin SZ and Xue LX: MicroRNA-9 functions as a tumor suppressor and enhances radio-sensitivity in radio-resistant A549 cells by targeting neuropilin 1. Oncol Lett. 15:2863–2870. 2018.PubMed/NCBI View Article : Google Scholar
11	Zhang Y, Wang Y and Wang J: MicroRNA-584 inhibits cell proliferation and invasion in non-small cell lung cancer by directly targeting MTDH. Exp Ther Med. 15:2203–2211. 2018.PubMed/NCBI View Article : Google Scholar
12	Kulda V, Svaton M, Mukensnabl P, Hrda K, Dvorak P, Houdek Z, Houfkova K, Vrzakova R, Babuska V, Pesek M and Pesta M: Predictive relevance of miR-34a, miR-224 and miR-342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy. Oncol Lett. 15:592–599. 2018.PubMed/NCBI View Article : Google Scholar
13	Zhang J, Wang T, Zhang Y, Wang H, Wu Y, Liu K and Pei C: Upregulation of serum miR-494 predicts poor prognosis in non-small cell lung cancer patients. Cancer Biomark. 21:763–768. 2018.PubMed/NCBI View Article : Google Scholar
14	Cao Q, Mao ZD, Shi YJ, Chen Y, Sun Y, Zhang Q, Song L and Peng LP: MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway. Oncotarget. 7:77468–77481. 2016.PubMed/NCBI View Article : Google Scholar
15	Luo J, Li H and Zhang C: MicroRNA-7 inhibits the malignant phenotypes of non-small cell lung cancer in vitro by targeting Pax6. Mol Med Rep. 12:5443–5448. 2015.PubMed/NCBI View Article : Google Scholar
16	Mou K, Gu W, Gu C, Zhang J, Qwang W, Ren G and Tian J: Relationship between miR-7 expression and treatment outcomes with gefitinib in non-small cell lung cancer. Oncol Lett. 12:4613–4617. 2016.PubMed/NCBI View Article : Google Scholar
17	Teufel A, Wong EA, Mukhopadhyay M, Malik N and Westphal H: FoxP4, a novel forkhead transcription factor. Biochim Biophys Acta. 1627:147–152. 2003.PubMed/NCBI View Article : Google Scholar
18	Tian W, Liu J, Pei B, Wang X, Guo Y and Yuan L: Identification of miRNAs and differentially expressed genes in early phase non-small cell lung cancer. Oncol Rep. 35:2171–2176. 2016.PubMed/NCBI View Article : Google Scholar
19	Yin Z, Ding H, He E, Chen J and Li M: Up-regulation of microRNA-491-5p suppresses cell proliferation and promotes apoptosis by targeting FOXP4 in human osteosarcoma. Cell Prolif. 50(e12308)2017.PubMed/NCBI View Article : Google Scholar
20	Wang G and Sun Y, He Y, Ji C, Hu B and Sun Y: MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box P4 (FOXP4). Int J Clin Exp Pathol. 8:337–344. 2015.PubMed/NCBI
21	Yang T, Li H, Thakur A, Chen T, Xue J, Li D and Chen M: FOXP4 modulates tumor growth and independently associates with miR-138 in non-small cell lung cancer cells. Tumour Biol. 36:8185–8191. 2015.PubMed/NCBI View Article : Google Scholar
22	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.PubMed/NCBI View Article : Google Scholar
23	Sin C, Li H and Crawford DA: Transcriptional regulation by FOXP1, FOXP2, and FOXP4 dimerization. J Mol Neurosci. 55:437–448. 2015.PubMed/NCBI View Article : Google Scholar
24	Song XL, Tang Y, Lei XH, Zhao SC and Wu ZQ: miR-618 inhibits prostate cancer migration and invasion by targeting FOXP2. J Cancer. 8:2501–2510. 2017.PubMed/NCBI View Article : Google Scholar
25	Da C, Liu Y, Zhan Y, Liu K and Wang R: Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway. Oncol Rep. 35:2767–2774. 2016.PubMed/NCBI View Article : Google Scholar
26	Hui Z, Yiling C, Wenting Y, XuQun H, ChuanYi Z and Hui L: miR-491-5p functions as a tumor suppressor by targeting JMJD2B in ERα-positive breast cancer. FEBS Lett. 589:812–821. 2015.PubMed/NCBI View Article : Google Scholar
27	Xu Y, Hou R, Lu Q, Zhang Y, Chen L, Zheng Y and Hu B: MiR-491-5p negatively regulates cell proliferation and motility by targeting PDGFRA in prostate cancer. Am J Cancer Res. 7:2545–2553. 2017.PubMed/NCBI
28	Sun R, Liu Z, Tong D, Yang Y, Guo B, Wang X, Zhao L and Huang C: miR-491-5p, mediated by Foxi1, functions as a tumor suppressor by targeting Wnt3a/β-catenin signaling in the development of gastric cancer. Cell Death Dis. 8(e2714)2017.PubMed/NCBI View Article : Google Scholar
29	Gong F, Ren P, Zhang Y, Jiang J and Zhang H: MicroRNAs-491-5p suppresses cell proliferation and invasion by inhibiting IGF2BP1 in non-small cell lung cancer. Am J Transl Res. 8:485–495. 2016.PubMed/NCBI
30	Sun D, Han S, Liu C, Zhou R, Sun W, Zhang Z and Qu J: Microrna-199a-5p functions as a tumor suppressor via suppressing connective tissue growth factor (CTGF) in follicular thyroid carcinoma. Med Sci Monit. 22:1210–1217. 2016.PubMed/NCBI View Article : Google Scholar
31	Zhang Q, Li Q, Xu T, Jiang H and Xu LG: miR-491-5p suppresses cell growth and invasion by targeting Notch3 in nasopharyngeal carcinoma. Oncol Rep. 35:3541–3547. 2016.PubMed/NCBI View Article : Google Scholar
32	Pirooz HJ, Jafari N, Rastegari M, Fathi-Roudsari M, Tasharrofi N, Shokri G, Tamadon M, Sazegar H and Kouhkan F: Functional SNP in microRNA-491-5p binding site of MMP9 3'-UTR affects cancer susceptibility. J Cell Biochem. 119:5126–5134. 2018.PubMed/NCBI View Article : Google Scholar
33	Stetler-Stevenson WG: The role of matrix metalloproteinases in tumor invasion, metastasis, and angiogenesis. Surg Oncol Clin N Am. 10:383–392. 2001.PubMed/NCBI
34	Kim S, Lee J, You D, Jeong Y, Jeon M, Yu J, Kim SW, Nam SJ and Lee JE: Berberine suppresses cell motility through downregulation of TGF-β1 in triple negative breast cancer cells. Cell Physiol Biochem. 45:795–807. 2018.PubMed/NCBI View Article : Google Scholar