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MicroRNA-143 act as a tumor suppressor microRNA in human lung cancer cells by inhibiting cell proliferation, invasion, and migration

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Abstract

Background/aim

MicroRNAs play crucial roles in controlling cellular biological processes. miR-143 expression is usually downregulated in different cancers. In this study, we focused on exploring the role of miR143 in NSCLC development.

Methods

Bioinformatics analyses were used to detect the expression level of miR-143 in lung tumors. The cells were transfected by pCMV-miR-143 vectors. The efficacy of transfection was verified by Flow cytometry. The influence of miR-143 replacement on NSCLC cells migration, proliferation, and apoptosis was detected using wound-healing assay, MTT assay, and DAPI staining, respectively.

Results

MTT assay revealed that overexpression of miR143 inhibited cell growth and proliferation. Scratch assay results demonstrated that restoration of miR143 suppressed cell migration. The qRT-PCR assay was further used to detect the assumed relationship between miR143 and apoptotic and metastatic-related genes.

Conclusion

The findings showed that miR-143 could reduce cell proliferation, invasion, and migration by reducing CXCR4, Vimentin, MMP-1, Snail-1, C-myc expression level, and increasing E-cadherin expression levels in lung cancer cells and might be a potential target in NSCLC’s targeted therapy.

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Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.

Abbreviations

LC:

Lung cancer.

SCLC:

Small cell lung carcinoma.

NSCLC:

Non-small cell lung cancer.

miRNAs:

MicroRNAs.

miR-143:

microRNA-143.

TCGA:

The Cancer Genome Atlas.

G418:

Geneticin.

FACS:

Fluorescence-activated cell sorting.

DAPI:

2-(4-amidinophenyl)-6-indolecarbamidine dihydrochloride.

M-MuLV RT:

Moloney murine leukemia virus.

SD:

Standard deviation.

NC:

Negative control.

TS miRNA:

Tumor suppressor miRNA.

OSCC:

Oral squamous cell carcinoma cells

EMT:

Epithelial-mesenchymal transition

MMP-1:

Matrix metalloproteinase 1

MMPs:

Matrix metalloproteinase

References

  1. Barta JA, Powell CA, Wisnivesky JP (2019)Global Epidemiology of Lung Cancer. Annals of global health, 85(1)

  2. Herbst RS, Morgensztern D, Boshoff C (2018) The biology and management of non-small cell lung cancer. Nature 553(7689):446

    Article  CAS  Google Scholar 

  3. Hosseinahli N et al (2018) Treating cancer with microRNA replacement therapy: A literature review. J Cell Physiol 233(8):5574–5588

    Article  CAS  Google Scholar 

  4. Ivey KN, Srivastava D (2015) microRNAs as developmental regulators. Cold Spring Harbor perspectives in biology, 7(7): p. a008144

  5. Ha M, Kim VN (2014) Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15(8):509

    Article  CAS  Google Scholar 

  6. Tavanafar F et al (2017) Restoration of miR-143 expression could inhibit migration and growth of MDA-MB-468 cells through down-regulating the expression of invasion-related factors, vol 91. Biomedicine & Pharmacotherapy, pp 920–924

  7. Zhang N, Su Y, Xu L (2013) Targeting PKCε by miR-143 regulates cell apoptosis in lung cancer. FEBS letters. 587:3661–366722

  8. Fan X et al (2013) Upregulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression. BMC cancer. 13:611

  9. Mallick R, Patnaik SK, Yendamuri S (2010)MicroRNAs and lung cancer: Biology and applications in diagnosis and prognosis. Journal of carcinogenesis, 9

  10. Mollaei H, Safaralizadeh R, Rostami Z (2019) MicroRNA Replace therapy cancer J Cell Physiol 234(8):12369–12384

    CAS  Google Scholar 

  11. Zhang P et al (2022) MicroRNA-143 expression inhibits the growth and the invasion of osteosarcoma. J Orthop Surg Res 17(1):1–15

    Article  Google Scholar 

  12. Yang H et al (2021) miR–143–3p inhibits endometriotic stromal cell proliferation and invasion by inactivating autophagy in endometriosis. Molecular medicine reports. 23:1–95

  13. Zhang C et al (2021) MiR-143-3p Inhibits Cell Proliferation in Pedatric Acute Myeloid Leukemia via Inhibition of KAT6A. Pediatric Hematology and Oncology, pp 1–11

  14. Ding C et al (2022) The anti-cancer role of microRNA-143 in papillary thyroid carcinoma by targeting high mobility group AT-hook 2. Bioengineered. 13:6629–66403

  15. Peng J et al (2021) miR-143-3p inhibits proliferation and invasion of hepatocellular carcinoma cells by regulating its target gene FGF1. Clinical and Translational Oncology. 23:468–4803

  16. Tang J et al (2021) MiR-495-3p and miR-143-3p co-target CDK1 to inhibit the development of cervical cancer. Clinical and Translational Oncology. 23:2323–233411

  17. Asghariazar V et al (2022) Restoration of miR-143 reduces migration and proliferation of bladder cancer cells by regulating signaling pathways involved in EMT. Molecular and Cellular Probes. 61:101794

  18. Mohammadi A et al (2021) Restoration of miR-330 expression suppresses lung cancer cell viability, proliferation, and migration. J Cell Physiol 236(1):273–283

    Article  CAS  Google Scholar 

  19. Asghariazar V et al (2019) Tumor suppressor microRNAs in lung cancer: An insight to signaling pathways and drug resistance. Journal of cellular biochemistry

  20. Karimi L et al (2017) Function of microRNA-143 in different signal pathways in cancer: New insights into cancer therapy, vol 91. Biomedicine & Pharmacotherapy, pp 121–131

  21. Wu B-L et al (2011) MiRNA profile in esophageal squamous cell carcinoma: downregulation of miR-143 and miR-145. World J Gastroenterol 17(1):79–88

    Article  CAS  Google Scholar 

  22. Liu L et al (2012) miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2. Molecular medicine reports. 5:753–7603

  23. Xia C et al (2018) MiR-143-3p inhibits the proliferation, cell migration and invasion of human breast cancer cells by modulating the expression of MAPK7. Biochimie, 147: p. 98–104

  24. Xia H et al (2014) miR-143 inhibits NSCLC cell growth and metastasis by targeting Limk1. Int J Mol Sci 15(7):11973–11983

    Article  Google Scholar 

  25. Karimi L et al (2019) miRNA-143 replacement therapy harnesses the proliferation and migration of colorectal cancer cells in vitro. Journal of cellular physiology

  26. Chen X et al (2009) Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene 28(10):1385

    Article  CAS  Google Scholar 

  27. Mesgarzadeh AH et al (2019) Transfection of microRNA-143 mimic could inhibit migration of HN-5 cells through down-regulating of metastatic genes. Gene, 716: p. 144033

  28. Hu Y et al (2012) miR-143 inhibits the metastasis of pancreatic cancer and an associated signaling pathway. Tumor Biology. 33:1863–18706

  29. Pozzobon T et al (2016) CXCR4 signaling in health and disease. Immunology letters, 177: p. 6–15

  30. Chatterjee S, Azad BB, Nimmagadda S (2014) The intricate role of CXCR4 in cancer, in Advances in cancer research. Elsevier, pp 31–82

  31. Yu T et al (2014) MicroRNA-9 inhibits the proliferation of oral squamous cell carcinoma cells by suppressing expression of CXCR4 via the Wnt/β-catenin signaling pathway. Oncogene, 33(42): p. 5017–5027

  32. Luo X et al (2018) Wnt inhibitory factor-1-mediated autophagy inhibits Wnt/β-catenin signaling by downregulating dishevelled-2 expression in non-small cell lung cancer cells. Int J Oncol 53(2):904–914

    CAS  PubMed  Google Scholar 

  33. Cano A et al (2000) The transcription factor snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2(2):76

    Article  CAS  Google Scholar 

  34. Diepenbruck M, Christofori G (2016) Epithelial–mesenchymal transition (EMT) and metastasis: yes, no, maybe? Current opinion in cell biology, 43: p. 7–13

  35. Chen T et al (2017) Epithelial–mesenchymal transition (EMT): a biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol 232(12):3261–3272

    Article  CAS  Google Scholar 

  36. He M et al (2017) MiR-143-5p deficiency triggers EMT and metastasis by targeting HIF-1α in gallbladder cancer. Cell Physiol Biochem 42(5):2078–2092

    Article  CAS  Google Scholar 

  37. Peng X et al (2011) Identification of miRs-143 and-145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PloS one. 6:e203415

  38. Jackstadt R, Hermeking H (2015) MicroRNAs as regulators and mediators of c-MYC function. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1849:544–5535

  39. Zhang Y et al (2015) Sp1 and c-Myc modulate drug resistance of leukemia stem cells by regulating survivin expression through the ERK-MSK MAPK signaling pathway. Molecular cancer. 14:561

  40. Chen Z et al (2010) miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc. J Experimental Clin Cancer Res 29(1):151

    Article  Google Scholar 

  41. Dong Y, Hu T (2018) Effects of miR-143 overexpression on proliferation, apoptosis, EGFR and downstream signaling pathways in PC9/GR cell line. cell. 80:4

  42. Hossian A et al (2018) Multipronged activity of combinatorial miR-143 and miR-506 inhibits lung cancer cell cycle progression and angiogenesis in vitro. Scientific reports. 8:1–141

  43. Liu M et al (2016) MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma. Cancer letters. 377:97–1041

  44. Kuliopulos A, Koukos G (2016) PAR-1 activation by metalloproteinase-1 (MMP-1). Google Patents

  45. Bibby BA et al (2019) Silencing microRNA-330-5p increases MMP1 expression and promotes an invasive phenotype in oesophageal adenocarcinoma. BMC Cancer 19(1):1–11

    Article  CAS  Google Scholar 

  46. Caley MP, Martins VL (2015) O’Toole, Metalloproteinases and wound healing. Advances in wound care. 4:225–2344

  47. Jiang Q et al (2019) Therapeutic delivery of microRNA-143 by cationic lipoplexes for non-small cell lung cancer treatment in vivo. J Cancer Res Clin Oncol 145(12):2951–2967

    Article  CAS  Google Scholar 

  48. Ma Q et al (2013) MicroRNA-143 inhibits migration and invasion of human non-small-cell lung cancer and its relative mechanism. International journal of biological sciences, 9(7): p. 680

  49. Shen Pf et al (2014) MicroRNA-494‐3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer. Prostate 74(7):756–767

    Article  CAS  Google Scholar 

  50. Ma F et al (2017) MiR-361-5p inhibits glycolytic metabolism, proliferation and invasion of breast cancer by targeting FGFR1 and MMP-1. J Experimental Clin Cancer Res 36(1):158

    Article  Google Scholar 

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Acknowledgements

The current study was performed with the financial assistance of Tabriz University of Medical Science, Tabriz, Iran (grant number 60131).

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Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Vahid Asghariazar & Ebrahim Sakhinia

  2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Vahid Asghariazar, Mahtab Kadkhodayi & Behzad Baradaran

  3. Cellular and Molecular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA

    Behzad Mansoori

  4. Department of Animal Biology, Faculty of Natural Sciences, The University of Tabriz, Tabriz, Iran

    Mahtab Kadkhodayi

  5. Department of Microbiology and Immunology, faculty of medicine, Ardabil university of medical sciences, Ardabil, Iran

    Elham Safarzadeh

  6. Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark

    Ali Mohammadi

  7. Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Ebrahim Sakhinia

  8. Tabriz Genetic Analysis Centre (TGAC), Tabriz University of Medical Sciences, Tabriz, Iran

    Ebrahim Sakhinia

  9. Immunology Research Center, Tabriz University of Medical Science, Beside Shahid GhaziTabatabaei Hospital, Gholghasht Ave, Tabriz, Iran

    Behzad Baradaran

Authors
  1. Vahid Asghariazar
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  2. Behzad Mansoori
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  3. Mahtab Kadkhodayi
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  4. Elham Safarzadeh
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  5. Ali Mohammadi
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  6. Behzad Baradaran
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  7. Ebrahim Sakhinia
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Contributions

Vahid Asghariazar wrote the original paper and carried out the experiments, Behzad Mansoori and Mahtab Kadkhodayi contributed to data collection; Elham Safarzadeh and Ali Mohammadi provided advice and consultation; Behzad Baradaran and Ebrahim Sakhinia contributed to the final revision of the manuscript, analyzed the statistical data and verified the accuracy of the tests. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Behzad Baradaran.

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Asghariazar, V., Mansoori, B., Kadkhodayi, M. et al. MicroRNA-143 act as a tumor suppressor microRNA in human lung cancer cells by inhibiting cell proliferation, invasion, and migration. Mol Biol Rep 49, 7637–7647 (2022). https://doi.org/10.1007/s11033-022-07580-1

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  • DOI: https://doi.org/10.1007/s11033-022-07580-1

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