Tumor Biology

, Volume 35, Issue 5, pp 3975–3979 | Cite as

MicroRNA-21 is a novel promising target in cancer radiation therapy

  • Jia Liu
  • Hongcheng Zhu
  • Xi Yang
  • Yangyang Ge
  • Chi Zhang
  • Qin Qin
  • Jing Lu
  • Liangliang Zhan
  • Hongyan Cheng
  • Xinchen Sun


MicroRNAs (miRNAs) represent an important nonprotein part of the human genome in tumor biology. Among the several types of miRNAs, microRNA-21 (miR-21) is dysregulated in several types of cancer and plays a key role in carcinogenesis, recurrence, and metastasis. Thus, it can be a potential target for cancer therapy including radiation therapy. In this review, we focus on miR-21, which has been identified in human cancer tissues, to suggest reasonable strategies for future research. miR-21 may have an influence on cell cycle, DNA damage repair, apoptosis, autophagy, and hypoxia of cancer during irradiation. We review the use of miR-21 in cancer radiation therapy and describe the known functions and possible underlying molecular mechanisms of miR-21 in radiosensitivity and radioresistance. Furthermore, the current and potential future applications of miR-21 in cancer radiation therapy are also discussed.


MicroRNA miR-21 Cancer Radiotherapy Radiosensitivity 



This work was supported by the Natural Science Foundation of China (No. 81272504), Innovation Team [No. LJ201123 (EH11)], A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) (JX10231801), grants from Key Academic Discipline of Jiangsu Province “Medical Aspects of Specific Environments”, Six Major Talent Peak Project of Jiangsu Province (2013-WSN-040), Jiangsu Provincial Science and Technology Projects [BK2011854 (DA11)], and “333” Project of Jiangsu Province [BRA2012210 (RS12)].

Conflicts of interest



  1. 1.
    Chatterjee S, Willis N, Locks SM, Mott JH, Kelly CG. Dosimetric and radiobiological comparison of helical tomotherapy, forward-planned intensity-modulated radiotherapy and two-phase conformal plans for radical radiotherapy treatment of head and neck squamous cell carcinomas. Br J Radiol. 2011;84:1083–90.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Joubert A, Vogin G, Devic C, Granzotto A, Viau M, Maalouf M, et al. Radiation biology: major advances and perspectives for radiotherapy. Cancer Radiotherapie : J de la Societe Francaise de Radiotherapie Oncologique. 2011;15:348–54.CrossRefGoogle Scholar
  3. 3.
    Janga SC, Vallabhaneni S. MicroRNAs as post-transcriptional machines and their interplay with cellular networks. Adv Exp Med Biol. 2011;722:59–74.CrossRefPubMedGoogle Scholar
  4. 4.
    Liu J, Zheng M, Tang YL, Liang XH, Yang Q. MicroRNAs, an active and versatile group in cancers. Int J Oral Sci. 2011;3:165–75.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Zhao L, Chen X, Cao Y. New role of microRNA: carcinogenesis and clinical application in cancer. Acta biochimica et biophysica Sinica. 2011;43:831–9.CrossRefPubMedGoogle Scholar
  6. 6.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65:6029–33.CrossRefPubMedGoogle Scholar
  8. 8.
    Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene. 2007;26:2799–803.CrossRefPubMedGoogle Scholar
  9. 9.
    Qian B, Katsaros D, Lu L, Preti M, Durando A, Arisio R, et al. High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-beta1. Breast cancer research and treatment. 2009;117:131–40.CrossRefPubMedGoogle Scholar
  10. 10.
    Markou A, Tsaroucha EG, Kaklamanis L, Fotinou M, Georgoulias V, Lianidou ES. Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clin Chem. 2008;54:1696–704.CrossRefPubMedGoogle Scholar
  11. 11.
    Li J, Huang H, Sun L, Yang M, Pan C, Chen W, et al. MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin Cancer Res: Off J Am Assoc Cancer Res. 2009;15:3998–4008.CrossRefGoogle Scholar
  12. 12.
    Chan SH, Wu CW, Li AF, Chi CW, Lin WC. miR-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res. 2008;28:907–11.PubMedGoogle Scholar
  13. 13.
    Li Y, Zhao S, Zhen Y, Li Q, Teng L, Asai A, et al. A miR-21 inhibitor enhances apoptosis and reduces G(2)-M accumulation induced by ionizing radiation in human glioblastoma U251 cells. Brain Tumor Pathol. 2011;28:209–14.CrossRefPubMedGoogle Scholar
  14. 14.
    Anastasov N, Hofig I, Vasconcellos IG, Rappl K, Braselmann H, Ludyga N, et al. Radiation resistance due to high expression of miR-21 and G2/M checkpoint arrest in breast cancer cells. Radiat Oncol. 2012;7:206.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gwak HS, Kim TH, Jo GH, Kim YJ, Kwak HJ, Kim JH, et al. Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. PloS One. 2012;7:e47449.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chao TF, Xiong HH, Liu W, Chen Y, Zhang JX. MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2, Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen Ban. 2013;33:525–9.Google Scholar
  17. 17.
    Boutros R, Dozier C, Ducommun B. The when and wheres of CDC25 phosphatases. Curr Opin Cell Biol. 2006;18:185–91.CrossRefPubMedGoogle Scholar
  18. 18.
    Ray D, Kiyokawa H. CDC25A phosphatase: a rate-limiting oncogene that determines genomic stability. Cancer Res. 2008;68:1251–3.CrossRefPubMedGoogle Scholar
  19. 19.
    Wang P, Zou F, Zhang X, Li H, Dulak A, Tomko Jr RJ, et al. microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. Cancer Res. 2009;69:8157–65.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gupta AK, Bakanauskas VJ, Cerniglia GJ, Cheng Y, Bernhard EJ, Muschel RJ, et al. The Ras radiation resistance pathway. Cancer Res. 2001;61:4278–82.PubMedGoogle Scholar
  21. 21.
    Grana TM, Rusyn EV, Zhou H, Sartor CI, Cox AD. Ras mediates radioresistance through both phosphatidylinositol 3-kinase-dependent and Raf-dependent but mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-independent signaling pathways. Cancer Res. 2002;62:4142–50.PubMedGoogle Scholar
  22. 22.
    Gupta AK, McKenna WG, Weber CN, Feldman MD, Goldsmith JD, Mick R, et al. Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin Cancer Res : Off J Am Assoc Cancer Res. 2002;8:885–92.Google Scholar
  23. 23.
    Lee CM, Fuhrman CB, Planelles V, Peltier MR, Gaffney DK, Soisson AP, et al. Phosphatidylinositol 3-kinase inhibition by LY294002 radiosensitizes human cervical cancer cell lines. Clin Cancer Res: An off J Am Assoc Cancer Res. 2006;12:250–6.CrossRefGoogle Scholar
  24. 24.
    Li B, Yuan M, Kim IA, Chang CM, Bernhard EJ, Shu HK. Mutant epidermal growth factor receptor displays increased signaling through the phosphatidylinositol-3 kinase/AKT pathway and promotes radioresistance in cells of astrocytic origin. Oncogene. 2004;23:4594–602.CrossRefPubMedGoogle Scholar
  25. 25.
    Rosenzweig KE, Youmell MB, Palayoor ST, Price BD. Radiosensitization of human tumor cells by the phosphatidylinositol3-kinase inhibitors wortmannin and LY294002 correlates with inhibition of DNA-dependent protein kinase and prolonged G2-M delay. Clin Cancer Res: An Off J Am Assoc Cancer Res. 1997;3:1149–56.Google Scholar
  26. 26.
    Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression. Cell. 2008;133:403–14.CrossRefPubMedGoogle Scholar
  28. 28.
    Chang F, Lee JT, Navolanic PM, Steelman LS, Shelton JG, Blalock WL, et al. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia. 2003;17:590–603.CrossRefPubMedGoogle Scholar
  29. 29.
    Puc J, Keniry M, Li HS, Pandita TK, Choudhury AD, Memeo L, et al. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer cell. 2005;7:193–204.CrossRefPubMedGoogle Scholar
  30. 30.
    Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 2006;130:2113–29.CrossRefPubMedGoogle Scholar
  31. 31.
    Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Wickramasinghe NS, Manavalan TT, Dougherty SM, Riggs KA, Li Y, Klinge CM. Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids Res. 2009;37:2584–95.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ma WJ, Lv GD, Tuersun A, Liu Q, Liu H, Zheng ST, et al. Role of microRNA-21 and effect on PTEN in Kazakh’s esophageal squamous cell carcinoma. Mol Biol Rep. 2011;38:3253–60.CrossRefPubMedGoogle Scholar
  34. 34.
    Huang S, Li XQ, Chen X, Che SM, Chen W, Zhang XZ. Inhibition of microRNA-21 increases radiosensitivity of esophageal cancer cells through phosphatase and tensin homolog deleted on chromosome 10 activation. Dis Esophagus: Off J Int Soc Dis Esophagus/ISDE. 2013;26:823–31.CrossRefGoogle Scholar
  35. 35.
    Liu ZL, Wang H, Liu J, Wang ZX. MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo- or radioresistance in non-small cell lung cancer cells by targeting PTEN. Mol Cell Biochem. 2013;372:35–45.CrossRefPubMedGoogle Scholar
  36. 36.
    Mathew R, Karantza-Wadsworth V, White E. Role of autophagy in cancer. Nature Reviews Cancer. 2007;7:961–7.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ito H, Aoki H, Kuhnel F, Kondo Y, Kubicka S, Wirth T, et al. Autophagic cell death of malignant glioma cells induced by a conditionally replicating adenovirus. J Natl Cancer Inst. 2006;98:625–36.CrossRefPubMedGoogle Scholar
  38. 38.
    Gewirtz DA, Hilliker ML, Wilson EN. Promotion of autophagy as a mechanism for radiation sensitization of breast tumor cells. Radiother Oncol: J Eur Soc Ther Radiol Oncol. 2009;92:323–8.CrossRefGoogle Scholar
  39. 39.
    Belozerov VE, Van Meir EG. Hypoxia inducible factor-1: a novel target for cancer therapy. Anti-cancer Drugs. 2005;16:901–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Yang Y, Sun M, Wang L, Jiao B. HIFs, angiogenesis, and cancer. J Cell Biochem. 2013;114:967–74.CrossRefPubMedGoogle Scholar
  41. 41.
    Meijer TW, Kaanders JH, Span PN, Bussink J. Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clin Cancer Res: Off J Am Assoc Cancer Res. 2012;18:5585–94.CrossRefGoogle Scholar
  42. 42.
    Mace TA, Collins AL, Wojcik SE, Croce CM, Lesinski GB, Bloomston M. Hypoxia induces the overexpression of microRNA-21 in pancreatic cancer cells. J Surg Res. 2013;184:855–60.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, et al. MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1alpha expression. PloS One. 2011;6:e19139.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Jia Liu
    • 1
  • Hongcheng Zhu
    • 1
  • Xi Yang
    • 1
  • Yangyang Ge
    • 2
  • Chi Zhang
    • 1
  • Qin Qin
    • 1
  • Jing Lu
    • 1
  • Liangliang Zhan
    • 1
  • Hongyan Cheng
    • 3
  • Xinchen Sun
    • 1
  1. 1.Department of Radiation Oncology, The First Affiliated HospitalNanjing Medical UniversityNanjingChina
  2. 2.Department of Radiation OncologyNantong Tumor Hospital Affiliated to Nantong UniversityNantongChina
  3. 3.Department of General Internal Medicine, The First Affiliated HospitalNanjing Medical UniversityNanjingChina

Personalised recommendations