Open Access

MicroRNA‑208a directly targets Src kinase signaling inhibitor 1 to facilitate cell proliferation and invasion in non‑small cell lung cancer

  • Authors:
    • Li Liu
    • Wuzhang Wang
    • Song Gao
    • Xiuwen Wang
  • View Affiliations

  • Published online on: July 31, 2019     https://doi.org/10.3892/mmr.2019.10542
  • Pages: 3140-3148
  • Copyright: © Liu 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: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The abnormal expression of microRNAs (miRNAs/miRs) has a critical function in the formation and progression of non‑small cell lung cancer (NSCLC). Therefore, understanding the association between NSCLC and dysregulated miRNAs may allow for the identification of novel diagnostic and therapeutic biomarkers for patients with this malignancy. Previous studies have validated miR‑208a as a cancer‑associated miRNA in multiple different types of human cancer, however, its expression pattern and precise function in NSCLC remains yet to be elucidated. Therefore, the aims of the present study were to measure miR‑208a expression in NSCLC, investigate its specific functions in NSCLC and determine its exact regulatory mechanisms. Herein, the results demonstrated that miR‑208a was significantly upregulated in NSCLC tissues and cell lines compared with that in adjacent non‑cancerous tissues and a non‑tumorigenic bronchial epithelium BEAS‑2B cell line (P<0.05, respectively). The high expression level of miR‑208a exhibited an obvious association with Tumor‑Node‑Metastasis stage and lymph node metastasis. MiR‑208a silencing decreased the proliferative and invasive capacities of NSCLC cells. Notably, Src kinase signaling inhibitor 1 (SRCIN1) was verified as a potential direct target gene of miR‑208a in NSCLC cells. Furthermore, SRCIN1 knockdown was able to rescue the miR‑208a‑mediated effects on NSCLC cells. In addition to this, silencing miR‑208a expression inhibited the extracellular regulated kinase (ERK) signaling pathway in NSCLC. Overall, to the best of our knowledge, the present study is the first to provide evidence that miR‑208a exerts oncogenic functions in the carcinogenesis and progression of NSCLC by directly targeting SRCIN1 and regulating the ERK pathway. Therefore, miR‑208a may be developed as a potential target for treating patients with NSCLC.

References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Latimer KM: Lung cancer: Clinical presentation and diagnosis. FP Essent. 464:23–26. 2018.PubMed/NCBI

4 

Gadgeel SM: New targets in non-small cell lung cancer. Curr Oncol Rep. 15:411–423. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Mott TF: Lung cancer: Management. FP Essent. 464:27–30. 2018.PubMed/NCBI

6 

Yu JL, Simmons C, Victor JC, Han D, Hogeveen S, Leighl N and Verma S: Impact of new chemotherapeutic and targeted agents on survival in stage IV non-small cell lung cancer. Oncologist. 16:1307–1315. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Parums DV: Current status of targeted therapy in non-small cell lung cancer. Drugs Today (Barc). 50:503–525. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Simon J: Technology radiation technology targets tumors. Surgical precision without the incision. S D Med. 67:3622014.PubMed/NCBI

9 

Miller YE: Pathogenesis of lung cancer: 100 year report. Am J Respir Cell Mol Biol. 33:216–223. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Diniz GP and Wang DZ: Regulation of skeletal muscle by microRNAs. Compr Physiol. 6:1279–1294. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Bao W, Greenwold MJ and Sawyer RH: Expressed miRNAs target feather related mRNAs involved in cell signaling, cell adhesion and structure during chicken epidermal development. Gene. 591:393–402. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Lin S and Gregory RI: MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 15:321–333. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Hata A and Lieberman J: Dysregulation of microRNA biogenesis and gene silencing in cancer. Sci Signal. 8:re32015. View Article : Google Scholar : PubMed/NCBI

16 

Zhang A, Lakshmanan J, Motameni A and Harbrecht BG: MicroRNA-203 suppresses proliferation in liver cancer associated with PIK3CA, p38 MAPK, c-Jun, and GSK3 signaling. Mol Cell Biochem. 441:89–98. 2018. View Article : Google Scholar : PubMed/NCBI

17 

Zhang Z, Yang Y and Zhang X: MiR-770 inhibits tumorigenesis and EMT by targeting JMJD6 and regulating WNT/β-catenin pathway in non-small cell lung cancer. Life Sci. 188:163–171. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Zhang X, Ma X, An H, Xu C, Cao W, Yuan W and Ma J: Upregulation of microRNA-125b by G-CSF promotes metastasis in colorectal cancer. Oncotarget. 8:50642–50654. 2017.PubMed/NCBI

19 

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Yu P, Wu D, You Y, Sun J, Lu L, Tan J and Bie P: miR-208-3p promotes hepatocellular carcinoma cell proliferation and invasion through regulating ARID2 expression. Exp Cell Res. 336:232–241. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Li H, Zheng D, Zhang B, Liu L, Ou J, Chen W, Xiong S, Gu Y and Yang J: Mir-208 promotes cell proliferation by repressing SOX6 expression in human esophageal squamous cell carcinoma. J Transl Med. 12:1962014. View Article : Google Scholar : PubMed/NCBI

22 

Yin K, Liu M, Zhang M, Wang F, Fen M, Liu Z, Yuan Y, Gao S, Yang L, Zhang W, et al: miR-208a-3p suppresses cell apoptosis by targeting PDCD4 in gastric cancer. Oncotarget. 7:67321–67332. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Chassagnon G, Bennani S and Revel MP: New TNM classification of non-small cell lung cancer. Rev Pneumol Clin. 73:34–39. 2017.(In French). View Article : Google Scholar : PubMed/NCBI

24 

Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Enright AJ, John B, Gaul U, Tuschl T, Sander C and Marks DS: MicroRNA targets in Drosophila. Genome Biol. 5:R12003. View Article : Google Scholar : PubMed/NCBI

26 

Cao M, Hou D, Liang H, Gong F, Wang Y, Yan X, Jiang X, Wang C, Zhang J, Zen K, et al: miR-150 promotes the proliferation and migration of lung cancer cells by targeting SRC kinase signalling inhibitor 1. Eur J Cancer. 50:1013–1024. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Ye L, Wang H and Liu B: miR-211 promotes non-small cell lung cancer proliferation by targeting SRCIN1. Tumour Biol. 37:1151–1157. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Gao Y, Xue Q, Wang D, Du M, Zhang Y and Gao S: miR-873 induces lung adenocarcinoma cell proliferation and migration by targeting SRCIN1. Am J Transl Res. 7:2519–2526. 2015.PubMed/NCBI

29 

Cao Y, Zhao D, Li P, Wang L, Qiao B, Qin X, Li L and Wang Y: MicroRNA-181a-5p impedes IL-17-induced nonsmall cell lung cancer proliferation and migration through targeting VCAM-1. Cell Physiol Biochem. 42:346–356. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Wang H, Zhan Y, Jin J, Zhang C and Li W: MicroRNA-15b promotes proliferation and invasion of non-small cell lung carcinoma cells by directly targeting TIMP2. Oncol Rep. 37:3305–3312. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Liu A, Shao C, Jin G, Liu R, Hao J, Song B, Ouyang L and Hu X: miR-208-induced epithelial to mesenchymal transition of pancreatic cancer cells promotes cell metastasis and invasion. Cell Biochem Biophys. 69:341–346. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Di Stefano P, Cabodi S, Boeri Erba E, Margaria V, Bergatto E, Giuffrida MG, Silengo L, Tarone G, Turco E and Defilippi P: P130Cas-associated protein (p140Cap) as a new tyrosine-phosphorylated protein involved in cell spreading. Mol Biol Cell. 15:787–800. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Chen R, Liao JY, Huang J, Chen WL, Ma XJ and Luo XD: Downregulation of SRC kinase signaling inhibitor 1 (SRCIN1) expression by MicroRNA-32 promotes proliferation and epithelial-mesenchymal transition in human liver cancer cells. Oncol Res. 26:573–579. 2018. View Article : Google Scholar : PubMed/NCBI

34 

Chen B, Pan W, Lin X, Hu Z, Jin Y, Chen H, Ma G, Qiu Y, Chang L, Hua C, et al: MicroRNA-346 functions as an oncogene in cutaneous squamous cell carcinoma. Tumour Biol. 37:2765–2771. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Yang F, Luo LJ, Zhang L, Wang DD, Yang SJ, Ding L, Li J, Chen D, Ma R, Wu JZ and Tang JH: MiR-346 promotes the biological function of breast cancer cells by targeting SRCIN1 and reduces chemosensitivity to docetaxel. Gene. 600:21–28. 2017. View Article : Google Scholar : PubMed/NCBI

36 

Wang P, Wang H, Li X, Liu Y, Zhao C and Zhu D: SRCIN1 suppressed osteosarcoma cell proliferation and invasion. PLoS One. 11:e01555182016. View Article : Google Scholar : PubMed/NCBI

37 

Wang H, Wu C, Wan S, Zhang H, Zhou S and Liu G: Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway. Toxicology. 308:104–112. 2013. View Article : Google Scholar : PubMed/NCBI

38 

Qi M, Tian Y, Li W, Li D, Zhao T, Yang Y, Li Q, Chen S, Yang Y, Zhang Z, et al: ERK inhibition represses gefitinib resistance in non-small cell lung cancer cells. Oncotarget. 9:12020–12034. 2018. View Article : Google Scholar : PubMed/NCBI

39 

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. View Article : Google Scholar : PubMed/NCBI

40 

Zhang L, Lin J, Ye Y, Oba T, Gentile E, Lian J, Wang J, Zhao Y, Gu J, Wistuba II, et al: Serum MicroRNA-150 predicts prognosis for early-stage non-small cell lung cancer and promotes tumor cell proliferation by targeting tumor suppressor gene SRCIN1. Clin Pharmacol Ther. 103:1061–1073. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2019
Volume 20 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Liu, L., Wang, W., Gao, S., & Wang, X. (2019). MicroRNA‑208a directly targets Src kinase signaling inhibitor 1 to facilitate cell proliferation and invasion in non‑small cell lung cancer. Molecular Medicine Reports, 20, 3140-3148. https://doi.org/10.3892/mmr.2019.10542
MLA
Liu, L., Wang, W., Gao, S., Wang, X."MicroRNA‑208a directly targets Src kinase signaling inhibitor 1 to facilitate cell proliferation and invasion in non‑small cell lung cancer". Molecular Medicine Reports 20.4 (2019): 3140-3148.
Chicago
Liu, L., Wang, W., Gao, S., Wang, X."MicroRNA‑208a directly targets Src kinase signaling inhibitor 1 to facilitate cell proliferation and invasion in non‑small cell lung cancer". Molecular Medicine Reports 20, no. 4 (2019): 3140-3148. https://doi.org/10.3892/mmr.2019.10542