Skip to main content

Advertisement

SpringerLink
Log in

MiR-590 suppresses the progression of non-small cell lung cancer by regulating YAP1 and Wnt/β-catenin signaling

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Objective

Accumulating evidence has been revealed that miR-590 is involved in the progression and carcinogenesis of various cancers. However, the molecular mechanism of miR-590 in non-small-cell lung cancer (NSCLC) remains unclear.

Methods

Quantitative reverse transcription-PCR (qRT-PCR), western blot, MTT, and transwell assay were applied to investigate the functional role of miR-590 in this study. Dual luciferase reporter assay was utilized to investigate the interaction between YAP1 and miR-590 expression. Cells transfected with miR-590 mimic or inhibitor were subjected to western blot to investigate the role of Wnt/β-catenin signaling in NSCLC modulated by miR-590.

Results

MiR-590 was down-regulated in NSCLC tissues and cells. Kaplan–Meier analysis found that the higher expression of miR-590 in NSCLC patients, the more improved survival rate of NSCLC patients. Over-expression of miR-590 inhibited NSCLC cell proliferation, migration, and invasion. Moreover, increasing miR-590 suppressed Yes-associated protein 1 (YAP1) expression and inhibited the Wnt/β-catenin pathway in NSCLC cells. Furthermore, miR-590 was negatively correlated with YAP1 expression.

Conclusion

These findings demonstrated that the miR-590/YAP1 axis exerted an important role in the progression of NSCLC, suggesting that miR-590 might be the appealing prognostic marker for NSCLC treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL, Paz-Ares L. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389:299–311. https://doi.org/10.1016/S0140-6736(16)30958-8.

    Article  CAS  PubMed  Google Scholar 

  2. Rosell R, Karachaliou N. Lung cancer in 2014: optimizing lung cancer treatment approaches. Nat Rev Clin Oncol. 2015;12(2015):75–6. https://doi.org/10.1038/nrclinonc.2014.225.

    Article  CAS  PubMed  Google Scholar 

  3. Spiegel ML, Goldman JW, Wolf BR, Nameth DJ, Grogan TR, Lisberg AE, Wong DJL, Ledezma BA, Mendenhall MA, Genshaft SJ, Gutierrez AJ, Abtin F, Wallace WD, Adame CR, McKenzie JR, Abarca PA, Li AJ, Strunck JL, Famenini S, Carroll JM, Tucker DA, Sauer LM, Moghadam NM, Elashoff DA, Abaya CD, Brennan MB, Garon EB. Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges. Cancer. 2017;123:4800–7. https://doi.org/10.1002/cncr.31056.

    Article  PubMed  Google Scholar 

  4. Brule SY, Al-Baimani K, Jonker H, Zhang T, Nicholas G, Goss G, Laurie SA, Wheatley-Price P. Palliative systemic therapy for advanced non-small cell lung cancer: investigating disparities between patients who are treated versus those who are not. Lung Cancer. 2016;97:15–21. https://doi.org/10.1016/j.lungcan.2016.04.007.

    Article  PubMed  Google Scholar 

  5. Nagasaka M, Gadgeel SM. Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer. Expert Rev Anticancer Ther. 2018;18:63–70. https://doi.org/10.1080/14737140.2018.1409624.

    Article  CAS  PubMed  Google Scholar 

  6. Ernani V, Steuer CE, Jahanzeb M. The end of nihilism: systemic therapy of advanced non-small cell lung cancer. Annu Rev Med. 2017;68:153–68. https://doi.org/10.1146/annurev-med-042915-102442.

    Article  CAS  PubMed  Google Scholar 

  7. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell. 2006;127:679–95. https://doi.org/10.1016/j.cell.2006.11.001.

    Article  CAS  PubMed  Google Scholar 

  8. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Investig. 2003;112:1776–84. https://doi.org/10.1172/JCI20530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, Baba H, Mori M. Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 2010;101:293–9. https://doi.org/10.1111/j.1349-7006.2009.01419.x.

    Article  CAS  PubMed  Google Scholar 

  10. Yang D, Sun Y, Hu L, Zheng H, Ji P, Pecot CV, Zhao Y, Reynolds S, Cheng H, Rupaimoole R, Cogdell D, Nykter M, Broaddus R, Rodriguez-Aguayo C, Lopez-Berestein G, Liu J, Shmulevich I, Sood AK, Chen K, Zhang W. Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer. Cancer Cell. 2013;23:186–99. https://doi.org/10.1016/j.ccr.2012.12.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhao B, Tumaneng K, Guan KL. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat Cell Biol. 2011;13:877–83. https://doi.org/10.1038/ncb2303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L, Zheng P, Ye K, Chinnaiyan A, Halder G, Lai ZC, Guan KL. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007;21:2747–61. https://doi.org/10.1101/gad.1602907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pan D. The Hippo signaling pathway in development and cancer. Dev Cell. 2010;19:491–505. https://doi.org/10.1016/j.devcel.2010.09.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mo JS, Park HW, Guan KL. The Hippo signaling pathway in stem cell biology and cancer. EMBO Rep. 2014;15:642–56. https://doi.org/10.15252/embr.201438638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sohn BH, Shim JJ, Kim SB, Jang KY, Kim SM, Kim JH, Hwang JE, Jang HJ, Lee HS, Kim SC, Jeong W, Kim SS, Park ES, Heo J, Kim YJ, Kim DG, Leem SH, Kaseb A, Hassan MM, Cha M, Chu IS, Johnson RL, Park YY, Lee JS. Inactivation of Hippo pathway is significantly associated with poor prognosis in hepatocellular carcinoma. Clin Cancer Res: Off J Am Assoc Cancer Res. 2016;22:1256–64. https://doi.org/10.1158/1078-0432.CCR-15-1447.

    Article  CAS  Google Scholar 

  16. Lee HJ, Diaz MF, Price KM, Ozuna JA, Zhang S, Sevick-Muraca EM, Hagan JP, Wenzel PL. Fluid shear stress activates YAP1 to promote cancer cell motility. Nat Commun. 2017;8:14122. https://doi.org/10.1038/ncomms14122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cui R, Meng W, Sun HL, Kim T, Ye Z, Fassan M, Jeon YJ, Li B, Vicentini C, Peng Y, Lee TJ, Luo Z, Liu L, Xu D, Tili E, Jin V, Middleton J, Chakravarti A, Lautenschlaeger T, Croce CM. MicroRNA-224 promotes tumor progression in nonsmall cell lung cancer. Proc Natl Acad Sci USA. 2015;112:E4288-4297. https://doi.org/10.1073/pnas.1502068112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Joshi P, Jeon YJ, Lagana A, Middleton J, Secchiero P, Garofalo M, Croce CM. MicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC. Proc Natl Acad Sci USA. 2015;112:8650–5. https://doi.org/10.1073/pnas.1500886112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cai J, Fang L, Huang Y, Li R, Yuan J, Yang Y, Zhu X, Chen B, Wu J, Li M. miR-205 targets PTEN and PHLPP2 to augment AKT signaling and drive malignant phenotypes in non-small cell lung cancer. Cancer Res. 2013;73:5402–15. https://doi.org/10.1158/0008-5472.CAN-13-0297.

    Article  CAS  PubMed  Google Scholar 

  20. Faversani A, Amatori S, Augello C, Colombo F, Porretti L, Fanelli M, Ferrero S, Palleschi A, Pelicci PG, Belloni E, Ercoli G, Degrassi A, Baccarin M, Altieri DC, Vaira V, Bosari S. miR-494–3p is a novel tumor driver of lung carcinogenesis. Oncotarget. 2017;8:7231–47. https://doi.org/10.18632/oncotarget.13933.

    Article  PubMed  Google Scholar 

  21. Abdolvahabi Z, Nourbakhsh M, Hosseinkhani S, Hesari Z, Alipour M, Jafarzadeh M, Ghorbanhosseini SS, Seiri P, Yousefi Z, Yarahmadi S, Golpour P. MicroRNA-590-3P suppresses cell survival and triggers breast cancer cell apoptosis via targeting sirtuin-1 and deacetylation of p53. J Cell Biochem. 2018. https://doi.org/10.1002/jcb.28211.

    Article  PubMed  Google Scholar 

  22. Wang WT, Qi Q, Zhao P, Li CY, Yin XY, Yan RB. miR-590–3p is a novel microRNA which suppresses osteosarcoma progression by targeting SOX9. Biomed Pharmacother. 2018;107:1763–9. https://doi.org/10.1016/j.biopha.2018.06.124.

    Article  CAS  PubMed  Google Scholar 

  23. Salem M, O’Brien JA, Bernaudo S, Shawer H, Ye G, Brkic J, Amleh A, Vanderhyden BC, Refky B, Yang BB, Krylov SN, Peng C. miR-590-3p promotes ovarian cancer growth and metastasis via a novel FOXA2-versican pathway. Can Res. 2018;78:4175–90. https://doi.org/10.1158/0008-5472.CAN-17-3014.

    Article  CAS  Google Scholar 

  24. Ma Z, Wang Y, He B, Cui J, Zhang C, Wang H, Feng W, Wang B, Wei D, Wu Y, Zeng Y, Yu G. Expression of miR-590 in lung cancer and its correlation with prognosis. Oncol Lett. 2018;15:1753–7. https://doi.org/10.3892/ol.2017.7497.

    Article  CAS  PubMed  Google Scholar 

  25. Xu BB, Gu ZF, Ma M, Wang JY, Wang HN. MicroRNA-590–5p suppresses the proliferation and invasion of non-small cell lung cancer by regulating GAB1. Eur Rev Med Pharmacol Sci. 2018;22:5954–63. https://doi.org/10.26355/eurrev_201809_15926.

    Article  PubMed  Google Scholar 

  26. Piao L, Wang F, Wang Y, Yang Z, Li Q, Cui L, Yu Q. miR-424-5p regulates hepatoma cell proliferation and apoptosis. Cancer Biother Radiopharm. 2019. https://doi.org/10.1089/cbr.2018.2625.

    Article  PubMed  Google Scholar 

  27. Sun Z, Ou C, Liu J, Chen C, Zhou Q, Yang S, Li G, Wang G, Song J, Li Z, Zhang Z, Yuan W, Li X. YAP1-induced MALAT1 promotes epithelial-mesenchymal transition and angiogenesis by sponging miR-126-5p in colorectal cancer. Oncogene. 2018. https://doi.org/10.1038/s41388-018-0628-y.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Liu G, Huang K, Jie Z, Wu Y, Chen J, Chen Z, Fang X, Shen S. CircFAT1 sponges miR-375 to promote the expression of yes-associated protein 1 in osteosarcoma cells. Mol Cancer. 2018;17:170. https://doi.org/10.1186/s12943-018-0917-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cheng H, Dong H, Feng J, Tian H, Zhang H, Xu L. miR-497 inhibited proliferation, migration and invasion of thyroid papillary carcinoma cells by negatively regulating YAP1 expression. Onco Targets Ther. 2018;11:4711–21. https://doi.org/10.2147/OTT.S164052.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chen M, Wu L, Tu J, Zhao Z, Fan X, Mao J, Weng Q, Wu X, Huang L, Xu M, Ji J. miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression. EBioMedicine. 2018;35:142–54. https://doi.org/10.1016/j.ebiom.2018.08.010.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Yu M, Luo Y, Cong Z, Mu Y, Qiu Y, Zhong M. MicroRNA-590-5p inhibits intestinal inflammation by targeting YAP. J Crohns Colitis. 2018;12:993–1004. https://doi.org/10.1093/ecco-jcc/jjy046.

    Article  PubMed  Google Scholar 

  32. Wei J, Jia A, Ma L, Wang Y, Qiu L, Xiao B. MicroRNA-16 inhibits the proliferation and metastasis of human lung cancer cells by modulating the expression of YAP1. J BUON. 2020;25:862–8.

    PubMed  Google Scholar 

  33. Ou C, Sun Z, Li X, Li X, Ren W, Qin Z, Zhang X, Yuan W, Wang J, Yu W, Zhang S, Peng Q, Yan Q, Xiong W, Li G, Ma J. MiR-590-5p, a density-sensitive microRNA, inhibits tumorigenesis by targeting YAP1 in colorectal cancer. Cancer Lett. 2017;399:53–63. https://doi.org/10.1016/j.canlet.2017.04.011.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. X. Hao and A. Su have contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China

    X. Hao

  2. General Department, Bejing Chaoyang District Sanhuan Cancer Hospital, Beijing, 100122, China

    A. Su

Authors
  1. X. Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XH conceived and designed the study, and drafted the manuscript. AS collected, analyzed and interpreted the experimental data. XH and AS revised the manuscript for important intellectual content. Both authors read and approved the final manuscript.

Corresponding author

Correspondence to X. Hao.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by Ethical Committee of Weifang Cancer Hospital and conducted in accordance with the ethical standards.

Informed consent

Subjects signed the informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 13 KB)

Supplementary file2 (DOCX 15 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hao, X., Su, A. MiR-590 suppresses the progression of non-small cell lung cancer by regulating YAP1 and Wnt/β-catenin signaling. Clin Transl Oncol 24, 546–555 (2022). https://doi.org/10.1007/s12094-021-02713-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-021-02713-7

Keywords

Search

Navigation