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microRNA-548l is involved in the migration and invasion of non-small cell lung cancer by targeting the AKT1 signaling pathway

  • Original Article – Cancer Research
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Abstract

Purpose

microRNAs (miRNAs) have been documented playing a critical role in cancer development and progression. In this study, we investigated the role of miR-548l in non-small cell lung cancer (NSCLC) migration and invasion.

Methods

microRNAs microarray analysis was used to detect the differentially expressed miRNAs between various metastatic levels of NSCLC cells and further confirmed by real-time PCR analysis. To facilitate the delineation of the role of selected miR-548l in NSCLC pathology, we detected its expression in 22 NSCLC tissues. Proliferation, apoptosis, invasion and metastasis effects of the miRNA were evaluated using MTT, flow cytometry, wound healing and invasion assay following transfection with mimics and inhibitors. Luciferase assay and Western blot analysis were performed to assess miR-548l binding to AKT1 gene. AKT1 expression in the clinical tissues was evaluated using immunohistochemical staining.

Results

The results showed a negative relationship between miR-548l expression and lymph node metastasis of NSCLC. Functional assays showed that over-expression of miR-548l suppressed NSCLC cell migration and invasion. Luciferase assays confirmed that miR-548l could directly bind to the 3′ untranslated region of AKT1. Further data showed that the over-expression of AKT1 could rescue the effects of miR-548l in NSCLC cells, and the miR-548l expression was inversely correlated with AKT1 expression in NSCLC tissues. These results indicated that AKT1 was involved in miR-548l-induced suppression of NSCLC cell migration and invasion.

Conclusion

These results suggested that miR-548l may play a causal role through AKT1 in NSCLC invasion and metastasis.

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References

  • Bueno MJ, Perez de Castro I, Malumbres M (2008) Control of cell proliferation pathways by microRNAs. Cell Cycle 7:3143–3148

    Article  CAS  PubMed  Google Scholar 

  • Cawston TE, Wilson AJ (2006) Understanding the role of tissue degrading enzymes and their inhibitors in development and disease. Best Pract Res Clin Rheumatol 20:983–1002

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Min L, Zhang X, Hu S, Wang B, Liu W, Wang R, Gu X, Shen W, Lv H et al (2013) Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer. Oncol Rep 30:1832–1840

    CAS  PubMed  Google Scholar 

  • Dilly AK, Ekambaram P, Guo Y, Cai Y, Tucker SC, Fridman R, Kandouz M, Honn KV (2013) Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasion via activation of PI3 K/Akt/NF-kappaB. Int J Cancer 133:1784–1791

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Du L, Schageman JJ, Subauste MC, Saber B, Hammond SM, Prudkin L, Wistuba II, Ji L, Roth JA, Minna JD, Pertsemlidis A (2009) miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. Mol Cancer Res 7:1234–1243

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781

    Article  CAS  PubMed  Google Scholar 

  • Franke TF (2008) PI3K/Akt: getting it right matters. Oncogene 27:6473–6488

    Article  CAS  PubMed  Google Scholar 

  • Karrasch T, Spaeth T, Allard B, Jobin C (2011) PI3K-dependent GSK3ss(Ser9)-phosphorylation is implicated in the intestinal epithelial cell wound-healing response. PLoS ONE 6:e26340

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ke Y, Zhao W, Xiong J, Cao R (2013) miR-149 inhibits non-small-cell lung cancer cells EMT by targeting FOXM1. Biochem Res Int 2013:506731

    Article  PubMed Central  PubMed  Google Scholar 

  • Kim EK, Yun SJ, Ha JM, Kim YW, Jin IH, Yun J, Shin HK, Song SH, Kim JH, Lee JS et al (2011) Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis. Oncogene 30:2954–2963

    Article  CAS  PubMed  Google Scholar 

  • Kim YW, Lee WH, Choi SM, Seo YY, Ahn BO, Kim SH, Kim SG (2012) DA6034 promotes gastric epithelial cell migration and wound-healing through the mTOR pathway. J Gastroenterol Hepatol 27:397–405

    Article  CAS  PubMed  Google Scholar 

  • Lee MW, Kim DS, Lee JH, Lee BS, Lee SH, Jung HL, Sung KW, Kim HT, Yoo KH, Koo HH (2011) Roles of AKT1 and AKT2 in non-small cell lung cancer cell survival, growth, and migration. Cancer Sci 102:1822–1828

    Article  CAS  PubMed  Google Scholar 

  • Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    Article  CAS  PubMed  Google Scholar 

  • Lima MH, Caricilli AM, de Abreu LL, Araujo EP, Pelegrinelli FF, Thirone AC, Tsukumo DM, Pessoa AF, dos Santos MF, de Moraes MA et al (2012) Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways: a double-blind placebo-controlled clinical trial. PLoS ONE 7:e36974

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lin RJ, Lin YC, Yu AL (2010) miR-149* induces apoptosis by inhibiting Akt1 and E2F1 in human cancer cells. Mol Carcinog 49:719–727

    CAS  PubMed  Google Scholar 

  • Mihai C, Bao S, Lai JP, Ghadiali SN, Knoell DL (2012) PTEN inhibition improves wound healing in lung epithelia through changes in cellular mechanics that enhance migration. Am J Physiol Lung Cell Mol Physiol 302:L287–L299

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rothschild SI (2013) Epigenetic therapy in lung cancer—role of microRNAs. Front Oncol 3:158

    Article  PubMed Central  PubMed  Google Scholar 

  • Sun W, Guo C, Meng X, Yu Y, Jin Y, Tong D, Geng J, Huang Q, Qi J, Liu A et al (2012) Differential expression of PAI-RBP1, C1orf142, and COTL1 in non-small cell lung cancer cell lines with different tumor metastatic potential. J Investig Med 60:689–694

    CAS  PubMed  Google Scholar 

  • Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, Kunkler I (2007) Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet Oncol 8:784–796

    Article  PubMed  Google Scholar 

  • Wang H, Zhu Y, Zhao M, Wu C, Zhang P, Tang L, Zhang H, Chen X, Yang Y, Liu G (2013a) miRNA-29c suppresses lung cancer cell adhesion to extracellular matrix and metastasis by targeting integrin beta1 and matrix metalloproteinase2 (MMP2). PLoS ONE 8:e70192

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang Y, Li CF, Pan LM, Gao ZL (2013b) 7,8-Dihydroxycoumarin inhibits A549 human lung adenocarcinoma cell proliferation by inducing apoptosis via suppression of Akt/NF-kappaB signaling. Exp Ther Med 5:1770–1774

    PubMed Central  PubMed  Google Scholar 

  • Wang YY, Ren T, Cai YY, He XY (2013c) MicroRNA let-7a inhibits the proliferation and invasion of nonsmall cell lung cancer cell line 95D by regulating K-Ras and HMGA2 gene expression. Cancer Biother Radiopharm 28:131–137

    Article  CAS  PubMed  Google Scholar 

  • Zhang JG, Guo JF, Liu DL, Liu Q, Wang JJ (2011) MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2. J Thorac Oncol 6:671–678

    Article  PubMed  Google Scholar 

  • Zhang N, Wang X, Huo Q, Sun M, Cai C, Liu Z, Hu G, Yang Q (2014) MicroRNA-30a suppresses breast tumor growth and metastasis by targeting metadherin. Oncogene 33:3119–3128

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Acknowledgments

This work was partly supported by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, the New Teachers’ Fund for Doctor Stations (No. 20100162120059), the Fundamental Research Funds for the Central Universities (No. 2011QNZT175) and the High Technology Project of Development and Reform Commission of Hunan (2013-1199).

Conflict of interest

The authors declare they have no conflict of interest.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha, China

    Caihong Liu, Huan Yang, Meiyu Zhou, Kui Xiao, Zhihui Shi, Lanyan Zhu & Rui Zhou

  2. Cancer Research Institute, Central South University, Changsha, China

    Zhijie Xu & Lifang Yang

  3. Department of Life Science, College of Biology, Hunan University, Changsha, China

    Dan Li

Authors
  1. Caihong Liu
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  2. Huan Yang
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  3. Zhijie Xu
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  4. Dan Li
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  5. Meiyu Zhou
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  6. Kui Xiao
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  7. Zhihui Shi
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  8. Lanyan Zhu
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  9. Lifang Yang
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  10. Rui Zhou
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Corresponding authors

Correspondence to Lifang Yang or Rui Zhou.

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Liu, C., Yang, H., Xu, Z. et al. microRNA-548l is involved in the migration and invasion of non-small cell lung cancer by targeting the AKT1 signaling pathway. J Cancer Res Clin Oncol 141, 431–441 (2015). https://doi.org/10.1007/s00432-014-1836-7

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  • DOI: https://doi.org/10.1007/s00432-014-1836-7

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