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miR-31-5p modulates cell progression in lung adenocarcinoma through TNS1/p53 axis

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Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Objective

To clarify the modulatory mechanism of miR-31-5p in lung adenocarcinoma (LUAD) progression in vivo and in vitro.

Methods

The Cancer Genome Atlas (TCGA) database was employed to access LUAD-related miRNA and mRNA expression data. Downstream targets of miR-31-5p were predicted by public databases. The interaction between miR-31-5p and TNS1 was determined by dual-luciferase reporter assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure miR-31-5p and TNS1 expression levels in LUAD cells. Western blot was introduced to test protein expression levels of TNS1, p53, and apoptosis-related proteins. In-vitro functional assays were conducted to evaluate the biological effects of miR-31-5p on cell proliferation, colony formation, migration, and apoptosis. In-vivo tumor xenograft experiment was applied to examine the effects of miR-31-5p on LUAD tumor growth, followed by immunochemistry assays for assessing TNS1 and p53 expression levels in the tumor tissue.

Results

miR-31-5p was prominently upregulated in LUAD tissue and was identified to present a similar trend in LUAD cell lines H1299, H23, and A549. miR-31-5p overexpression exerted an active role in cell proliferation and migration, but it suppressed cell apoptosis. Additionally, a reverse correlation between miR-31-5p and TNS1 regarding the expression level was identified, and TNS1 was verified to be a direct target of miR-31-5p. Besides, it was further validated by the rescue experiments that the tumor-promoting effects of miR-31-5p on LUAD cell functions were attenuated by TNS1 overexpression to some extent. The results based on the tumor xenograft experiment revealed that LUAD cell growth could be facilitated by miR-31-5p via the TNS1/p53 axis.

Conclusion

miR-31-5p facilitates LUAD cell progression mediated by the TNS1/p53 axis.

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References

  1. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34. https://doi.org/10.3322/caac.21551

    Article  PubMed  Google Scholar 

  2. Carrato A et al (2014) Clinical management patterns and treatment outcomes in patients with non-small cell lung cancer (NSCLC) across Europe: EPICLIN-lung study. Curr Med Res Opin 30:447–461. https://doi.org/10.1185/03007995.2013.860372

    Article  CAS  PubMed  Google Scholar 

  3. Ferlay J et al (2019) Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 144:1941–1953. https://doi.org/10.1002/ijc.31937

    Article  CAS  PubMed  Google Scholar 

  4. The Cancer Genome Atlas Research Network (2018) Author correction: comprehensive molecular profiling of lung adenocarcinoma. Nature 559:E12. https://doi.org/10.1038/s41586-018-0228-6

    Article  CAS  Google Scholar 

  5. Pang B et al (2017) Overexpression of RCC2 enhances cell motility and promotes tumor metastasis in lung adenocarcinoma by inducing epithelial-mesenchymal transition. Clin Cancer Res 23:5598–5610. https://doi.org/10.1158/1078-0432.CCR-16-2909

    Article  CAS  PubMed  Google Scholar 

  6. Zheng H, Liu JY, Song FJ, Chen KX (2013) Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer. Cancer Biol Med 10:123–130. https://doi.org/10.7497/j.issn.2095-3941.2013.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Summerer I et al (2013) Changes in circulating microRNAs after radiochemotherapy in head and neck cancer patients. Radiat Oncol 8:296. https://doi.org/10.1186/1748-717X-8-296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Domingues C et al (2018) Epithelial-mesenchymal transition and microRNAs: challenges and future perspectives in oral cancer. Head Neck 40:2304–2313. https://doi.org/10.1002/hed.25381

    Article  PubMed  Google Scholar 

  9. He J et al (2020) Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma. Int J Cancer 146:1052–1063. https://doi.org/10.1002/ijc.32543

    Article  CAS  PubMed  Google Scholar 

  10. Lu Z et al (2019) miR-31-5p is a potential circulating biomarker and therapeutic target for oral cancer. Mol Ther Nucleic Acids 16:471–480. https://doi.org/10.1016/j.omtn.2019.03.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Peng H et al (2019) MiR-31-5p promotes the cell growth, migration and invasion of colorectal cancer cells by targeting NUMB. Biomed Pharmacother 109:208–216. https://doi.org/10.1016/j.biopha.2018.10.048

    Article  CAS  PubMed  Google Scholar 

  12. Chen X et al (2019) Down-regulation of miR-31-5p inhibits proliferation and invasion of osteosarcoma cells through Wnt/beta-catenin signaling pathway by enhancing AXIN1. Exp Mol Pathol 108:32–41. https://doi.org/10.1016/j.yexmp.2019.03.001

    Article  CAS  PubMed  Google Scholar 

  13. Que KT et al (2018) MiR-31-5p regulates chemosensitivity by preventing the nuclear location of PARP1 in hepatocellular carcinoma. J Exp Clin Cancer Res 37:268. https://doi.org/10.1186/s13046-018-0930-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Borel JF (1986) Cyclosporine forever? Transplant Proc 18:271–272

    CAS  PubMed  Google Scholar 

  15. Lin K et al (2016) MicroRNA expression profiles predict progression and clinical outcome in lung adenocarcinoma. Onco Targets Ther 9:5679–5692. https://doi.org/10.2147/OTT.S111241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lin Y et al (2018) Four-miRNA signature as a prognostic tool for lung adenocarcinoma. Onco Targets Ther 11:29–36. https://doi.org/10.2147/OTT.S155016

    Article  PubMed  Google Scholar 

  17. Lv C et al (2017) MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists. Nat Commun 8:1036. https://doi.org/10.1038/s41467-017-01059-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang N, Li Y, Zhou J (2017) miR-31 functions as an oncomir which promotes epithelial-mesenchymal transition via regulating BAP1 in cervical cancer. Biomed Res Int 2017:6361420. https://doi.org/10.1155/2017/6361420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shi J et al (2018) MiR-31 mediates inflammatory signaling to promote re-epithelialization during skin wound healing. J Invest Dermatol 138:2253–2263. https://doi.org/10.1016/j.jid.2018.03.1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Brunner M et al (2011) Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent fibronectin deposition. J Cell Biol 194:307–322. https://doi.org/10.1083/jcb.201007108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chen J (2016) The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb Perspect Med 6:a26104. https://doi.org/10.1101/cshperspect.a026104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Garzon R, Marcucci G, Croce CM (2010) Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov 9:775–789. https://doi.org/10.1038/nrd3179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222. https://doi.org/10.1038/nrd.2016.246

    Article  CAS  PubMed  Google Scholar 

  24. Tang C et al (2020) LncRNA MAGI2-AS3 inhibits bladder cancer progression by targeting the miR-31-5p/TNS1 axis. Aging (Albany NY) 12:25547–25563. https://doi.org/10.18632/aging.104162

    Article  CAS  Google Scholar 

  25. Soler Artigas M et al (2011) Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function. Am J Respir Crit Care Med 184:786–795. https://doi.org/10.1164/rccm.201102-0192OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Shih YP, Sun P, Wang A, Lo SH (2015) Tensin1 positively regulates RhoA activity through its interaction with DLC1. Biochim Biophys Acta 1853:3258–3265. https://doi.org/10.1016/j.bbamcr.2015.09.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Burghel GJ et al (2013) Identification of candidate driver genes in common focal chromosomal aberrations of microsatellite stable colorectal cancer. PLoS One 8:e83859. https://doi.org/10.1371/journal.pone.0083859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Lung Cancer Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, 300060, Tianjin, China

    Chaonan Zhu, Bin Zhang, Wuhao Huang, Xiaoyan Sun & Changli Wang MD

  2. Department of Thoracic Surgery, North China University of Science and Technology Affiliated Hospital, 063000, Tangshan, China

    Shuai Wang, Maogen Zheng, Zhiquan Chen & Guochen Wang

  3. Department of Thoracic Surgery, Shanxi Provincial People’s Hospital, 030012, Taiyuan, China

    Jun Ma

Authors
  1. Chaonan Zhu
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  2. Shuai Wang
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  4. Zhiquan Chen
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  5. Guochen Wang
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  6. Jun Ma
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  10. Changli Wang MD
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Corresponding author

Correspondence to Changli Wang MD.

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Conflict of interest

C. Zhu, S. Wang, M. Zheng, Z. Chen, G. Wang, J. Ma, B. Zhang, W. Huang, X. Sun, and C. Wang declare that they have no competing interests.

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Availability of data and materials

The data and materials in the current study are available from the corresponding author on reasonable request.

Supplementary Information

Supplementary Table 1: Primer sequence for cell transfection and qRT-PCR

Supplementary Table 2: Antibodies for western blot and immunohistochemistry

66_2021_1895_MOESM3_ESM.tif

Supplementary Fig. 1: (A) Relationship between miR-31-5p and patients’ survival; (B) relationship between TNS1 and patients’ survival; (C) relationship between miR-31-5p/TNS1 and patients’ survival; (D, E) univariate and multivariate cox regression on miR-31-5p and TNS1 combined with the common clinical features

Supplementary data 1 Details of GSEA method

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Zhu, C., Wang, S., Zheng, M. et al. miR-31-5p modulates cell progression in lung adenocarcinoma through TNS1/p53 axis. Strahlenther Onkol 198, 304–314 (2022). https://doi.org/10.1007/s00066-021-01895-x

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  • DOI: https://doi.org/10.1007/s00066-021-01895-x

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