MicroRNA-20a promotes proliferation and invasion by directly targeting early growth response 2 in non‑small cell lung carcinoma

Wei,Lai; Ran,Fengming

doi:10.3892/ol.2017.7299

MicroRNA-20a promotes proliferation and invasion by directly targeting early growth response 2 in non‑small cell lung carcinoma

Authors:
- Lai Wei
- Fengming Ran
View Affiliations

Affiliations: Department of Chest Radiotherapy, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China, First Department of Thoracic Surgery, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China
Published online on: October 31, 2017 https://doi.org/10.3892/ol.2017.7299
Pages: 271-277
Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNA‑20a (miR‑20a) serves a notable role in tumor development and progression; it functions differently in different types of malignant tumor, and its role and mechanism in non‑small cell lung carcinoma (NSCLC) remains unclear. In the present study, the effects of miR‑20a on the proliferation and invasion of NSCLC cells and the underlying mechanisms behind this were investigated. Reverse transcription‑quantitative polymerase chain reaction revealed that the expression level of miR‑20a was higher in human NSCLC than in normal tissues. Following this, the effect of miR‑20a on the proliferation, apoptosis, migration and invasion of NSCLCA‑549 cells was further evaluated. In vitro analysis, including a Cell Counting Kit‑8, colony formation and Transwell migration assay, indicated that miR‑20a‑knockdown inhibited the proliferation, invasion and migration, while promoting the cell apoptosis of the A‑549 cells. Early growth response 2 (EGR2) protein and mRNA levels were downregulated or upregulated following the overexpression or knockdown of miR‑20a, respectively. Dual‑luciferase reporter gene assays implied that EGR2 is a direct target gene of miR‑20a. The results of the present study indicated that miR‑20a may function as an oncomiR in the development of NSCLC by promoting cell viability and motility. The inhibition of miR‑20a could even become a novel therapeutic method for the treatment of NSCLC.

View Figures

View References

1	Siegel R, Naishadham D and Jemal A: Cancer statistics 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
3	Laskin JJ and Sandler AB: State of the art in therapy for non-small cell lung cancer. Cancer Invest. 23:427–442. 2005. View Article : Google Scholar : PubMed/NCBI
4	Ferguson MK: Diagnosing and staging of non-small cell lung cancer. Hematol Oncol Clin North Am. 4:1053–1068. 1990.PubMed/NCBI
5	Del Vescovo V, Grasso M, Barbareschi M and Denti MA: MicroRNAs as lung cancer biomarkers. World J Clin Oncol. 5:604–620. 2014. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Schickel R, Boyerinas B, Park SM and Peter ME: MicroRNAs: Key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 27:5959–5974. 2008. View Article : Google Scholar : PubMed/NCBI
8	Yang T, Thakur A, Chen T, Yang L, Lei G, Liang Y, Zhang S, Ren H and Chen M: MicroRNA-15a induces cell apoptosis and inhibits metastasis by targeting BCL2L2 in non-small cell lung cancer. Tumour Biol. 36:4357–4365. 2015. View Article : Google Scholar : PubMed/NCBI
9	Chen CZ and Lodish HF: MicroRNAs as regulators of mammalian hematopoiesis. Semin Immunol. 17:155–165. 2005. View Article : Google Scholar : PubMed/NCBI
10	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nature Rev Cancer. 6:857–866. 2006. View Article : Google Scholar
11	Li J, Wang Y, Song Y, Fu Z and Yu W: miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells. Mol Cancer. 13:1932014. View Article : Google Scholar : PubMed/NCBI
12	Xiong S, Zheng Y, Jiang P, Liu R, Liu X and Chu Y: MicroRNA-7 inhibits the growth of human non-small cell lung cancer A-549 cells through targeting BCL-2. Int J Biol Sci. 7:805–814. 2011. View Article : Google Scholar : PubMed/NCBI
13	Guan P, Yin Z, Li X, Wu W and Zhou B: Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J Exp Clin Cancer Res. 31:542012. View Article : Google Scholar : PubMed/NCBI
14	Tsuchida A, Ohno S, Wu W, Borjigin N, Fujita K, Aoki T, Ueda S, Takanashi M and Kuroda M: miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer. Cancer Sci. 102:2264–2271. 2011. View Article : Google Scholar : PubMed/NCBI
15	Yoshino H, Seki N, Itesako T, Chiyomaru T, Nakagawa M and Enokida H: Aberrant expression of microRNAs in bladder cancer. Nat Rev Urol. 10:396–404. 2013. View Article : Google Scholar : PubMed/NCBI
16	Li X, Pan JH, Song B, Xiong EQ, Chen ZW, Zhou ZS and Su YP: Suppression of CX43 expression by miR-20a in the progression of human prostate cancer. Cancer Biol Ther. 13:890–898. 2012. View Article : Google Scholar : PubMed/NCBI
17	Chang CC, Yang YJ, Li YJ, Chen ST, Lin BR, Wu TS, Lin SK, Kuo MY and Tan CT: MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma. Oral Oncol. 49:923–931. 2013. View Article : Google Scholar : PubMed/NCBI
18	Fan MQ, Huang CB, Gu Y, Xiao Y, Sheng JX and Zhong L: Decrease expression of microRNA-20a promotes cancer cell proliferation and predicts poor survival of hepatocellular carcinoma. J Exp Clin Cancer Res. 32:212013. View Article : Google Scholar : PubMed/NCBI
19	Xia Y, Chen Q, Zhong Z, Xu C, Wu C, Liu B and Chen Y: Down-regulation of miR-30c promotes the invasion of non-small cell lung cancer by targeting MTA1. Cell Physiol Biochem. 32:476–485. 2013. View Article : Google Scholar : PubMed/NCBI
20	Zhang H, Zhang H, Zhao M, Lv Z, Zhang X, Qin X, Wang H, Wang S, Su J, Lv X, et al: MiR-138 inhibits tumor growth through repression of EZH2 in non-small cell lung cancer. Cell Physiol Biochem. 31:56–65. 2013. View Article : Google Scholar : PubMed/NCBI
21	Wu N, Zhang C, Bai C, Han YP and Li Q: MiR-4782-3p inhibited non-small cell lung cancer growth via USP14. Cell Physiol Biochem. 33:457–467. 2014. View Article : Google Scholar : PubMed/NCBI
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. View Article : Google Scholar : PubMed/NCBI
23	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. ELife. 4:102015. View Article : Google Scholar
24	Betel D, Wilson M, Gabow A, Marks DS and Sander C: The microRNA.org resource: Targets and expression. Nucleic Acids Res. 36:D149–D153. 2008. View Article : Google Scholar : PubMed/NCBI
25	Wong N and Wang X: miRDB: An online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 43(Database issue): D146–D152. 2015. View Article : Google Scholar : PubMed/NCBI
26	Cho WC: OncomiRs: The discovery and progress of microRNAs in cancers. Mol Cancer. 6:602007. View Article : Google Scholar : PubMed/NCBI
27	Chang Y, Liu C, Yang J, Liu G, Feng F, Tang J, Hu L, Li L, Jiang F, Chen C, et al: MiR-20a triggers metastasis of gallbladder carcinoma. J Hepatol. 59:518–527. 2013. View Article : Google Scholar : PubMed/NCBI
28	O'Donnell KA, Wentzel EA, Zeller KI, Dang CV and Mendell JT: c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 435:839–843. 2005. View Article : Google Scholar : PubMed/NCBI
29	Zhou J, Liu R, Luo C, Zhou X, Xia K, Chen X, Zhou M, Zou Q, Cao P and Cao K: MiR-20a inhibits cutaneous squamous cell carcinoma metastasis and proliferation by directly targeting LIMK1. Cancer Biol Ther. 15:1340–1349. 2014. View Article : Google Scholar : PubMed/NCBI
30	Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, et al: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 299:425–436. 2008. View Article : Google Scholar : PubMed/NCBI
31	Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stühler K, Meyer HE and Reifenberger G: Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol. 20:539–550. 2010. View Article : Google Scholar : PubMed/NCBI
32	Zhang G, Liu X, Wang W, Cai Y, Li S, Chen Q, Liao M, Zhang M, Zeng G, Zhou B, et al: Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages. Cell Cycle. 15:2527–2538. 2016. View Article : Google Scholar : PubMed/NCBI
33	Joseph LJ, le Beau MM, Jamieson GA Jr, Acharya S, Shows TB, Rowley JD and Sukhatme VP: Molecular cloning, sequencing and mapping of EGR2, a human early growth response gene encoding a protein with ‘zinc-binding finger’ structure. Proc Natl Acad Sci USA. 85:pp. 7164–7168. 1988; View Article : Google Scholar : PubMed/NCBI
34	Dzialo-Hatton R, Milbrandt J, Hockett RD Jr and Weaver CT: Differential expression of Fas ligand in Th1 and Th2 cells is regulated by early growth response gene and NF-AT family members. J Immunol. 166:4534–4542. 2001. View Article : Google Scholar : PubMed/NCBI
35	Unoki M and Nakamura Y: Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene. 20:4457–4465. 2001. View Article : Google Scholar : PubMed/NCBI
36	Wu Q, Jin H, Yang Z, Luo G, Lu Y, Li K, Ren G, Su T, Pan Y, Feng B, et al: miR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2. Biochem Biophys Res Commun. 392:340–345. 2010. View Article : Google Scholar : PubMed/NCBI