Skip to main content

Advertisement

Log in

RETRACTED ARTICLE: MicroRNA-92a promotes growth, metastasis, and chemoresistance in non-small cell lung cancer cells by targeting PTEN

  • Original Article
  • Published:
Tumor Biology

21 December 2021 This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.3233/TUB-219010 "

Abstract

MicroRNA-92a (miR-92a) has been reported to play important roles in tumorigenesis of human various cancers. However, the roles and underlying molecular mechanism of miR-92a in non-small cell lung cancer (NSCLC) have not been totally elucidated. Therefore, the aims of this study were to determine the role of miR-92a and to elucidate its regulatory mechanism in NSCLC. We found that miR-92a was significantly upregulated in NSCLC tissues compared to matched adjacent normal lung tissues, and its expression is significantly associated with clinical characteristics of patients, including tumor, node, and metastasis (TNM) stage; tumor size; and lymph node metastasis (all P < 0.01). Function assays demonstrated that upregulation of miR-92a in NSCLC cells promoted cell proliferation, migration, and invasion, decreased apoptosis and caspase-3 activity, and enhanced chemoresistance of NSCLC cells, whereas downregulation of miR-92a showed the opposite effects. Moreover, phosphatase and tensin homolog (PTEN), a unique tumor suppressor gene, was confirmed as a direct target of miR-92a, and PTEN messenger RNA (mRNA) expression was decreased in NSCLC tissues and was inversely correlated with miR-92a. Downregulation of PTEN could mimic the same effects of miR-92a mimic in NSCLC cells and rescue the effects on NSCLC cells induced by miR-92a inhibitor. Taken together, these findings suggested that miR-92a could promote growth, metastasis, and chemoresistance in NSCLC cells at least partially by targeting PTEN.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Change history

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    PubMed  Google Scholar 

  2. Sechler M, Cizmic AD, Avasarala S, Van Scoyk M, Brzezinski C, Kelley N, et al. Non-small-cell lung cancer: molecular targeted therapy and personalized medicine—drug resistance, mechanisms, and strategies. Pharmacogenomics Pers Med. 2013;6:25–36.

    Google Scholar 

  3. Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006;5:219–34.

    CAS  PubMed  Google Scholar 

  4. Toyooka S, Mitsudomi T, Soh J, Aokage K, Yamane M, Oto T, et al. Molecular oncology of lung cancer. Gen Thorac Cardiovasc Surg. 2011;59:527–37.

    PubMed  Google Scholar 

  5. Brennecke J, Cohen SM. Towards a complete description of the microRNA complement of animal genomes. Genome Biol. 2003;4:228.

    PubMed  PubMed Central  Google Scholar 

  6. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.

    CAS  PubMed  Google Scholar 

  7. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    CAS  PubMed  Google Scholar 

  8. Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell. 2009;136:642–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.

    CAS  PubMed  Google Scholar 

  10. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    CAS  PubMed  Google Scholar 

  11. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ma J, Dong C, Ji C. MicroRNA and drug resistance. Cancer Gene Ther. 2010;17:523–31.

    CAS  PubMed  Google Scholar 

  13. Hummel R, Hussey DJ, Haier J. MicroRNAs: predictors and modifiers of chemo- and radiotherapy in different tumour types. Eur J Cancer. 2010;46:298–311.

    CAS  PubMed  Google Scholar 

  14. Tutar Y. miRNA and cancer; computational and experimental approaches. Curr Pharm Biotechnol. 2014;15:429.

    CAS  PubMed  Google Scholar 

  15. Skrzypski M, Dziadziuszko R, Jassem J. MicroRNA in lung cancer diagnostics and treatment. Mutat Res. 2011;717:25–31.

    CAS  PubMed  Google Scholar 

  16. Sharifi M, Salehi R, Gheisari Y, Kazemi M. Inhibition of microRNA miR-92a induces apoptosis and necrosis in human acute promyelocytic leukemia. Adva Biomed Res. 2014;3:61.

    Google Scholar 

  17. Li M, Guan X, Sun Y, Mi J, Shu X, Liu F, et al. Mir-92a family and their target genes in tumorigenesis and metastasis. Exp Cell Res. 2014;323:1–6.

    CAS  PubMed  Google Scholar 

  18. He G, Zhang L, Li Q, Yang L. miR-92a/DUSP10/JNK signalling axis promotes human pancreatic cancer cells proliferation = Biomedicine & pharmacotherapy. Biomed Pharmacother. 2014;68:25–30.

    CAS  PubMed  Google Scholar 

  19. Ohyagi-Hara C, Sawada K, Kamiura S, Tomita Y, Isobe A, Hashimoto K, et al. miR-92a inhibits peritoneal dissemination of ovarian cancer cells by inhibiting integrin alpha5 expression. Am J Pathol. 2013;182:1876–89.

    CAS  PubMed  Google Scholar 

  20. Niu H, Wang K, Zhang A, Yang S, Song Z, Wang W, et al. miR-92a is a critical regulator of the apoptosis pathway in glioblastoma with inverse expression of bcl2l11. Oncol Rep. 2012;28:1771–7.

    CAS  PubMed  Google Scholar 

  21. Yoshizawa S, Ohyashiki JH, Ohyashiki M, Umezu T, Suzuki K, Inagaki A, et al. Downregulated plasma miR-92a levels have clinical impact on multiple myeloma and related disorders. Blood Cancer J. 2012;2, e53.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Lin HY, Chiang CH, Hung WC. STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells. Br J Cancer. 2013;109:731–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang J, Han L, Ge Y, Zhou X, Zhang A, Zhang C, et al. miR-221/222 promote malignant progression of glioma through activation of the Akt pathway. Int J Oncol. 2010;36:913–20.

    CAS  PubMed  Google Scholar 

  24. Feng B, Zhang K, Wang R, Chen L. Non-small-cell lung cancer and miRNAs: novel biomarkers and promising tools for treatment. Clin Sci. 2015;128:619–34.

    CAS  Google Scholar 

  25. Tsuchida A, Ohno S, Wu W, Borjigin N, Fujita K, Aoki T, et al. miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer. Cancer Sci. 2011;102:2264–71.

    CAS  PubMed  Google Scholar 

  26. Ohyashiki K, Umezu T, Yoshizawa S, Ito Y, Ohyashiki M, Kawashima H, et al. Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin’s lymphoma. PLoS ONE. 2011;6, e16408.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Nilsson S, Moller C, Jirstrom K, Lee A, Busch S, Lamb R, et al. Downregulation of miR-92a is associated with aggressive breast cancer features and increased tumour macrophage infiltration. PLoS ONE. 2012;7, e36051.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang G, Zhou H, Xiao H, Liu Z, Tian H, Zhou T. MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN. Dig Dis Sci. 2014;59:98–107.

    CAS  PubMed  Google Scholar 

  29. Chen ZL, Zhao XH, Wang JW, Li BZ, Wang Z, Sun J, et al. MicroRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via e-cadherin. J Biol Chem. 2011;286:10725–34.

    CAS  PubMed  Google Scholar 

  30. Zhou C, Shen L, Mao L, Wang B, Li Y, Yu H. miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7. Biochem Biophys Res Commun. 2015;458:63–9.

    CAS  PubMed  Google Scholar 

  31. Chun-Zhi Z, Lei H, An-Ling Z, Yan-Chao F, Xiao Y, Guang-Xiu W, et al. MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN. BMC Cancer. 2010;10:367.

    PubMed  PubMed Central  Google Scholar 

  32. Tang JM, He QY, Guo RX, Chang XJ. Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer. 2006;51:181–91.

    PubMed  Google Scholar 

  33. Xu HJ, Xu K, Zhou Y, Li J, Benedict WF, Hu SX. Enhanced tumor cell growth suppression by an n-terminal truncated retinoblastoma protein. Proc Natl Acad Sci U S A. 1994;91:9837–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Vatsyayan R, Chaudhary P, Lelsani PC, Singhal P, Awasthi YC, Awasthi S, et al. Role of RLIP76 in doxorubicin resistance in lung cancer. Int J Oncol. 2009;34:1505–11.

    CAS  PubMed  Google Scholar 

  35. Singhal SS, Yadav S, Singhal J, Drake K, Awasthi YC, Awasthi S. The role of PKCalpha and RLIP76 in transport-mediated doxorubicin-resistance in lung cancer. FEBS Lett. 2005;579:4635–41.

    CAS  PubMed  Google Scholar 

  36. Injac R, Strukelj B. Recent advances in protection against doxorubicin-induced toxicity. Technol Cancer Res Treatment. 2008;7:497–516.

    CAS  Google Scholar 

  37. Roca-Alonso L, Castellano L, Mills A, Dabrowska AF, Sikkel MB, Pellegrino L, et al. Myocardial miR-30 downregulation triggered by doxorubicin drives alterations in beta-adrenergic signaling and enhances apoptosis. Cell Death Dis. 2015;6, e1754.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Tormo E, Pineda B, Serna E, Guijarro A, Ribas G, Fores J, Chirivella E, Climent J, Lluch A, Eroles P: MicroRNA profile in response to doxorubicin treatment in breast cancer. Journal of cellular biochemistry 2015.

  39. Zhu X, Li H, Long L, Hui L, Chen H, Wang X, et al. miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor a. Acta Biochim Biophys Sin. 2012;44:519–26.

    CAS  PubMed  Google Scholar 

  40. Zhong S, Li W, Chen Z, Xu J, Zhao J. miR-222 and miR-29a contribute to the drug-resistance of breast cancer cells. Gene. 2013;531:8–14.

    CAS  PubMed  Google Scholar 

  41. Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, et al. miR-221&222 regulate trail resistance and enhance tumorigenicity through PTEN and timp3 downregulation. Cancer Cell. 2009;16:498–509.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Li N, Yang L, Wang H, Yi T, Jia X, Chen C, et al. miR-130a and miR-374a function as novel regulators of cisplatin resistance in human ovarian cancer a2780 cells. PLoS ONE. 2015;10, e0128886.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hong Zhang.

Ethics declarations

Conflicts of interest

None

Additional information

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.3233/TUB-219010"

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ren, P., Gong, F., Zhang, Y. et al. RETRACTED ARTICLE: MicroRNA-92a promotes growth, metastasis, and chemoresistance in non-small cell lung cancer cells by targeting PTEN. Tumor Biol. 37, 3215–3225 (2016). https://doi.org/10.1007/s13277-015-4150-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4150-3

Keywords

Navigation