Emerging role of microRNA-21 in cancer (Review)

  • Authors:
    • Yin-Hsun Feng
    • Chao-Jung Tsao
  • View Affiliations

  • Published online on: August 26, 2016     https://doi.org/10.3892/br.2016.747
  • Pages: 395-402
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

MicroRNAs (miRs) are a class of single-stranded RNA molecules of 15-27 nucleotides in length that regulate gene expression at the post-translational level. miR-21 is one of the earliest identified cancer-promoting ‘oncomiRs’, targeting numerous tumor suppressor genes associated with proliferation, apoptosis and invasion. The regulation of miR-21 and its role in carcinogenesis have been extensively investigated. Recent studies have focused on the diagnostic and prognostic value of miR-21 as well as its implication in the drug resistance of human malignancies. The further use of miR-21 as a biomarker and target for cancer treatments is likely to improve the outcome for patients with cancer. The present review highlights recent findings associated with the importance of miR-21 in hematological and non-hematological malignancies.

References

1 

Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A and Enright AJ: miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34:D140–D144. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Kim VN: MicroRNA biogenesis: Coordinated cropping and dicing. Nat Rev Mol Cell Biol. 6:376–385. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Feng YH, Wu CL, Tsao CJ, Chang JG, Lu PJ, Yeh KT, Uen YH, Lee JC and Shiau AL: Deregulated expression of sprouty2 and microRNA-21 in human colon cancer: Correlation with the clinical stage of the disease. Cancer Biol Ther. 11:111–121. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S, Castellano L, Magrelli A, Citarella F, Messina M, et al: Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood. 109:4944–4951. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Medina PP, Nolde M and Slack FJ: OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature. 467:86–90. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Sheedy FJ: Turning 21: Induction of miR-21 as a key switch in the inflammatory response. Front Immunol. 6:192015. View Article : Google Scholar : PubMed/NCBI

8 

Ma X, Conklin DJ, Li F, Dai Z, Hua X, Li Y, Xu-Monette ZY, Young KH, Xiong W, Wysoczynski M, et al: The oncogenic microRNA miR-21 promotes regulated necrosis in mice. Nat Commun. 6:71512015. View Article : Google Scholar : PubMed/NCBI

9 

Krichevsky AM and Gabriely G: miR-21: A small multi-faceted RNA. J Cell Mol Med. 13:39–53. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Selcuklu SD, Donoghue MT and Spillane C: miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 37:918–925. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Chan JA, Krichevsky AM and Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 65:6029–6033. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, et al: MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 24:4677–4684. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Tatsuguchi M, Seok HY, Callis TE, Thomson JM, Chen JF, Newman M, Rojas M, Hammond SM and Wang DZ: Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. J Mol Cell Cardiol. 42:1137–1141. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H, Dean DB and Zhang C: MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res. 100:1579–1588. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, et al: A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 129:1401–1414. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Lu TX, Munitz A and Rothenberg ME: MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol. 182:4994–5002. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Lu TX, Hartner J, Lim EJ, Fabry V, Mingler MK, Cole ET, Orkin SH, Aronow BJ and Rothenberg ME: MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J Immunol. 187:3362–3373. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Murugaiyan G, Garo LP and Weiner HL: MicroRNA-21, T helper lineage and autoimmunity. Oncotarget. 6:9644–9645. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Fujita S, Ito T, Mizutani T, Minoguchi S, Yamamichi N, Sakurai K and Iba H: miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. J Mol Biol. 378:492–504. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Pan X, Wang ZX and Wang R: MicroRNA-21: A novel therapeutic target in human cancer. Cancer Biol Ther. 10:1224–1232. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Löffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermüller J, Kretzschmar AK, Burger R, Gramatzki M, Blumert C, Bauer K, et al: Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood. 110:1330–1333. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, et al: MicroRNA signatures in human ovarian cancer. Cancer Res. 67:8699–8707. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Yang HS, Knies JL, Stark C and Colburn NH: Pdcd4 suppresses tumor phenotype in JB6 cells by inhibiting AP-1 transactivation. Oncogene. 22:3712–3720. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Hatley ME, Patrick DM, Garcia MR, Richardson JA, Bassel-Duby R, van Rooij E and Olson EN: Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer Cell. 18:282–293. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Zhu S, Si ML, Wu H and Mo YY: MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 282:14328–14336. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Schramedei K, Mörbt N, Pfeifer G, Läuter J, Rosolowski M, Tomm JM, von Bergen M, Horn F and Brocke-Heidrich K: MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4. Oncogene. 30:2975–2985. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Zhu S, Wu H, Wu F, Nie D, Sheng S and Mo YY: MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 18:350–359. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS and Krichevsky AM: MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol. 28:5369–5380. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Thorland EC, Myers SL, Gostout BS and Smith DI: Common fragile sites are preferential targets for HPV16 integrations in cervical tumors. Oncogene. 22:1225–1237. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST and Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 133:647–658. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Wu H, Ng R, Chen X, Steer CJ and Song G: MicroRNA-21 is a potential link between non-alcoholic fatty liver disease and hepatocellular carcinoma via modulation of the HBP1-p53-Srebp1c pathway. Gut gutjnl-2014-308430. 2015.

32 

Gu L, Song G, Chen L, Nie Z, He B, Pan Y, Xu Y, Li R, Gao T, Cho WC, et al: Inhibition of miR-21 induces biological and behavioral alterations in diffuse large B-cell lymphoma. Acta Haematol. 130:87–94. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, et al: Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 463:88–92. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Pfeifer M, Grau M, Lenze D, Wenzel SS, Wolf A, Wollert-Wulf B, Dietze K, Nogai H, Storek B, Madle H, et al: PTEN loss defines a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma. Proc Natl Acad Sci USA. 110:12420–12425. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Hong JY, Hong ME, Choi MK, Kim YS, Chang W, Maeng CH, Park S, Lee SJ, Do IG, Jo JS, et al: The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: A clinicopathological study of 262 cases. Ann Oncol. 25:182–188. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Go H, Jang JY, Kim PJ, Kim YG, Nam SJ, Paik JH, Kim TM, Heo DS, Kim CW and Jeon YK: MicroRNA-21 plays an oncogenic role by targeting FOXO1 and activating the PI3K/AKT pathway in diffuse large B-cell lymphoma. Oncotarget. 6:15035–15049. 2015. View Article : Google Scholar : PubMed/NCBI

37 

Karube K, Nakagawa M, Tsuzuki S, Takeuchi I, Honma K, Nakashima Y, Shimizu N, Ko YH, Morishima Y, Ohshima K, et al: Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses. Blood. 118:3195–3204. 2011. View Article : Google Scholar : PubMed/NCBI

38 

Yin Q, McBride J, Fewell C, Lacey M, Wang X, Lin Z, Cameron J and Flemington EK: MicroRNA-155 is an Epstein-Barr virus-induced gene that modulates Epstein-Barr virus-regulated gene expression pathways. J Virol. 82:5295–5306. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Chen W, Wang H, Chen H, Liu S, Lu H, Kong D, Huang X, Kong Q and Lu Z: Clinical significance and detection of microRNA-21 in serum of patients with diffuse large B-cell lymphoma in Chinese population. Eur J Haematol. 92:407–412. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Jones K, Nourse JP, Keane C, Bhatnagar A and Gandhi MK: Plasma microRNA are disease response biomarkers in classical Hodgkin lymphoma. Clin Cancer Res. 20:253–264. 2014. View Article : Google Scholar : PubMed/NCBI

41 

Anger B, Carbonell F, Braunger I, Heinze B, Gutensohn W, Thiel E and Heimpel H: Blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia (CML). Treatment results of 69 patients. Blut. 57:131–137. 1988. View Article : Google Scholar : PubMed/NCBI

42 

Zhou M, Zeng J, Wang X, Wang X, Huang T, Fu Y, Sun T, Jia J and Chen C: Histone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid leukemia. Oncotarget. 6:1249–1261. 2015. View Article : Google Scholar : PubMed/NCBI

43 

Ruiz-Lafuente N, Alcaraz-García MJ, Sebastián-Ruiz S, García-Serna AM, Gómez-Espuch J, Moraleda JM, Minguela A, García-Alonso AM and Parrado A: IL-4 up-regulates MiR-21 and the MiRNAs hosted in the CLCN5 gene in chronic lymphocytic leukemia. PLoS One. 10:e01249362015. View Article : Google Scholar : PubMed/NCBI

44 

Rossi S, Shimizu M, Barbarotto E, Nicoloso MS, Dimitri F, Sampath D, Fabbri M, Lerner S, Barron LL, Rassenti LZ, et al: microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood. 116:945–952. 2010. View Article : Google Scholar : PubMed/NCBI

45 

Riccioni R, Lulli V, Castelli G, Biffoni M, Tiberio R, Pelosi E, Lo-Coco F and Testa U: miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias. Leuk Res. 39:221–228. 2015. View Article : Google Scholar : PubMed/NCBI

46 

Junker F, Chabloz A, Koch U and Radtke F: Dicer1 imparts essential survival cues in Notch-driven T-ALL via miR-21-mediated tumor suppressor Pdcd4 repression. Blood. 126:993–1004. 2015. View Article : Google Scholar : PubMed/NCBI

47 

Leone E, Morelli E, Di Martino MT, Amodio N, Foresta U, Gullà A, Rossi M, Neri A, Giordano A, Munshi NC, et al: Targeting miR-21 inhibits in vitro and in vivo multiple myeloma cell growth. Clin Cancer Res. 19:2096–2106. 2013. View Article : Google Scholar : PubMed/NCBI

48 

Wang JH, Zhou WW, Cheng ST, Liu BX, Liu FR and Song JQ: Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells. Mol Med Rep. 12:1810–1816. 2015.PubMed/NCBI

49 

Wang W, Li J, Zhu W, Gao C, Jiang R, Li W, Hu Q and Zhang B: MicroRNA-21 and the clinical outcomes of various carcinomas: A systematic review and meta-analysis. BMC Cancer. 14:8192014. View Article : Google Scholar : PubMed/NCBI

50 

Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX and Shao JY: MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 14:2348–2360. 2008. View Article : Google Scholar : PubMed/NCBI

51 

Zhang ZJ and Ma SL: miRNAs in breast cancer tumorigenesis (Review). Oncol Rep. 27:903–910. 2012.PubMed/NCBI

52 

Venturutti L, Romero LV, Urtreger AJ, Chervo MF, Russo RI Cordo, Mercogliano MF, Inurrigarro G, Pereyra MG, Proietti CJ, Izzo F, et al: Stat3 regulates ErbB-2 expression and co-opts ErbB-2 nuclear function to induce miR-21 expression, PDCD4 downregulation and breast cancer metastasis. Oncogene. 35:2208–2222. 2015. View Article : Google Scholar : PubMed/NCBI

53 

Erbes T, Hirschfeld M, Rücker G, Jaeger M, Boas J, Iborra S, Mayer S, Gitsch G and Stickeler E: Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker. BMC Cancer. 15:1932015. View Article : Google Scholar : PubMed/NCBI

54 

Li S, Yang X, Yang J, Zhen J and Zhang D: Serum microRNA-21 as a potential diagnostic biomarker for breast cancer: A systematic review and meta-analysis. Clin Exp Med. 16:29–35. 2014. View Article : Google Scholar : PubMed/NCBI

55 

Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S and Allgayer H: MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 27:2128–2136. 2008. View Article : Google Scholar : PubMed/NCBI

56 

Yu Y, Nangia-Makker P, Farhana LG, Rajendra S, Levi E and Majumdar AP: miR-21 and miR-145 cooperation in regulation of colon cancer stem cells. Mol Cancer. 14:982015. View Article : Google Scholar : PubMed/NCBI

57 

Dong Y, Yu J and Ng SS: MicroRNA dysregulation as a prognostic biomarker in colorectal cancer. Cancer Manag Res. 6:405–422. 2014.PubMed/NCBI

58 

Nielsen BS, Jørgensen S, Fog JU, Søkilde R, Christensen IJ, Hansen U, Brünner N, Baker A, Møller S and Nielsen HJ: High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients. Clin Exp Metastasis. 28:27–38. 2011. View Article : Google Scholar : PubMed/NCBI

59 

Zhang JX, Song W, Chen ZH, Wei JH, Liao YJ, Lei J, Hu M, Chen GZ, Liao B, Lu J, et al: Prognostic and predictive value of a microRNA signature in stage II colon cancer: A microRNA expression analysis. Lancet Oncol. 14:1295–1306. 2013. View Article : Google Scholar : PubMed/NCBI

60 

Seike M, Goto A, Okano T, Bowman ED, Schetter AJ, Horikawa I, Mathe EA, Jen J, Yang P, Sugimura H, et al: miR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci USA. 106:12085–12090. 2009. View Article : Google Scholar : PubMed/NCBI

61 

Ma XL, Liu L, Liu XX, Li Y, Deng L, Xiao ZL, Liu YT, Shi HS and Wei YQ: Prognostic role of microRNA-21 in non-small cell lung cancer: A meta-analysis. Asian Pac J Cancer Prev. 13:2329–2334. 2012. View Article : Google Scholar : PubMed/NCBI

62 

Fu X, Han Y, Wu Y, Zhu X, Lu X, Mao F, Wang X, He X and Zhao Y and Zhao Y: Prognostic role of microRNA-21 in various carcinomas: A systematic review and meta-analysis. Eur J Clin Invest. 41:1245–1253. 2011. View Article : Google Scholar : PubMed/NCBI

63 

Wang X, Zhang J, Zhou L, Lu P, Zheng ZG, Sun W, Wang JL, Yang XS, Li XL, Xia N, et al: Significance of serum microRNA-21 in diagnosis of hepatocellular carcinoma (HCC): Clinical analyses of patients and an HCC rat model. Int J Clin Exp Pathol. 8:1466–1478. 2015.PubMed/NCBI

64 

Ribas J, Ni X, Haffner M, Wentzel EA, Salmasi AH, Chowdhury WH, Kudrolli TA, Yegnasubramanian S, Luo J, Rodriguez R, et al: miR-21: An androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. Cancer Res. 69:7165–7169. 2009. View Article : Google Scholar : PubMed/NCBI

65 

Reis ST, Pontes-Junior J, Antunes AA, Dall'Oglio MF, Dip N, Passerotti CC, Rossini GA, Morais DR, Nesrallah AJ, Piantino C, et al: miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer. BMC Urol. 12:142012. View Article : Google Scholar : PubMed/NCBI

66 

Coppola V, Musumeci M, Patrizii M, Cannistraci A, Addario A, Maugeri-Saccà M, Biffoni M, Francescangeli F, Cordenonsi M, Piccolo S, et al: BTG2 loss and miR-21 upregulation contribute to prostate cell transformation by inducing luminal markers expression and epithelial-mesenchymal transition. Oncogene. 32:1843–1853. 2013. View Article : Google Scholar : PubMed/NCBI

67 

Li T, Li RS, Li YH, Zhong S, Chen YY, Zhang CM, Hu MM and Shen ZJ: miR-21 as an independent biochemical recurrence predictor and potential therapeutic target for prostate cancer. J Urol. 187:1466–1472. 2012. View Article : Google Scholar : PubMed/NCBI

68 

Samsonov R, Shtam T, Burdakov V, Glotov A, Tsyrlina E, Berstein L, Nosov A, Evtushenko V, Filatov M and Malek A: Lectin-induced agglutination method of urinary exosomes isolation followed by mi-RNA analysis: Application for prostate cancer diagnostic. Prostate. 76:68–79. 2016. View Article : Google Scholar : PubMed/NCBI

69 

Koppers-Lalic D, Hackenberg M, de Menezes R, Misovic B, Wachalska M, Geldof A, Zini N, de Reijke T, Wurdinger T, Vis A, et al: Non-invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles. Oncotarget. 7:22566–22578. 2016.PubMed/NCBI

70 

Hong L, Han Y, Zhang Y, Zhang H, Zhao Q, Wu K and Fan D: MicroRNA-21: A therapeutic target for reversing drug resistance in cancer. Expert Opin Ther Targets. 17:1073–1080. 2013. View Article : Google Scholar : PubMed/NCBI

71 

Chen Z, Yuan YC, Wang Y, Liu Z, Chan HJ and Chen S: Down-regulation of programmed cell death 4 (PDCD4) is associated with aromatase inhibitor resistance and a poor prognosis in estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 152:29–39. 2015. View Article : Google Scholar : PubMed/NCBI

72 

Yu X, Li R, Shi W, Jiang T, Wang Y, Li C and Qu X: Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells. Biomed Pharmacother. 77:37–44. 2016. View Article : Google Scholar : PubMed/NCBI

73 

Bourguignon LY, Spevak CC, Wong G, Xia W and Gilad E: Hyaluronan-CD44 interaction with protein kinase C(epsilon) promotes oncogenic signaling by the stem cell marker Nanog and the Production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells. J Biol Chem. 284:26533–26546. 2009. View Article : Google Scholar : PubMed/NCBI

74 

Gong C, Yao Y, Wang Y, Liu B, Wu W, Chen J, Su F, Yao H and Song E: Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem. 286:19127–19137. 2011. View Article : Google Scholar : PubMed/NCBI

75 

Müller V, Gade S, Steinbach B, Loibl S, von Minckwitz G, Untch M, Schwedler K, Lübbe K, Schem C, Fasching PA, et al: Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: A translational research project within the Geparquinto trial. Breast Cancer Res Treat. 147:61–68. 2014. View Article : Google Scholar : PubMed/NCBI

76 

Deng J, Lei W, Fu JC, Zhang L, Li JH and Xiong JP: Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro. Biochem Biophys Res Commun. 443:789–795. 2014. View Article : Google Scholar : PubMed/NCBI

77 

Li B, Ren S, Li X, Wang Y, Garfield D, Zhou S, Chen X, Su C, Chen M, Kuang P, et al: miR-21 overexpression is associated with acquired resistance of EGFR-TKI in non-small cell lung cancer. Lung Cancer. 83:146–153. 2014. View Article : Google Scholar : PubMed/NCBI

78 

Shen H, Zhu F, Liu J, Xu T, Pei D, Wang R, Qian Y, Li Q, Wang L, Shi Z, et al: Alteration in Mir-21/PTEN expression modulates gefitinib resistance in non-small cell lung cancer. PLoS One. 9:e1033052014. View Article : Google Scholar : PubMed/NCBI

79 

Wang S, Su X, Bai H, Zhao J, Duan J, An T, Zhuo M, Wang Z, Wu M, Li Z, et al: Identification of plasma microRNA profiles for primary resistance to EGFR-TKIs in advanced non-small cell lung cancer (NSCLC) patients with EGFR activating mutation. J Hematol Oncol. 8:1272015. View Article : Google Scholar : PubMed/NCBI

80 

Wu ZH, Tao ZH, Zhang J, Li T, Ni C, Xie J, Zhang JF and Hu XC: miRNA-21 induces epithelial to mesenchymal transition and gemcitabine resistance via the PTEN/AKT pathway in breast cancer. Tumour Biol. 37:7245–7254. 2016. View Article : Google Scholar : PubMed/NCBI

81 

Yu Y, Kanwar SS, Patel BB, Oh PS, Nautiyal J, Sarkar FH and Majumdar AP: MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFβR2) in colon cancer cells. Carcinogenesis. 33:68–76. 2012. View Article : Google Scholar : PubMed/NCBI

82 

Feng YH, Wu CL, Shiau AL, Lee JC, Chang JG, Lu PJ, Tung CL, Feng LY, Huang WT and Tsao CJ: MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells. Int J Mol Med. 29:920–926. 2012.PubMed/NCBI

83 

Liu ZL, Wang H, Liu J and 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. 372:35–45. 2013. View Article : Google Scholar : PubMed/NCBI

84 

Wei X, Wang W, Wang L, Zhang Y, Zhang X, Chen M, Wang F, Yu J, Ma Y and Sun G: MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4. Cancer Med. 5:693–702. 2016. View Article : Google Scholar : PubMed/NCBI

85 

Paik WH, Kim HR, Park JK, Song BJ, Lee SH and Hwang JH: Chemosensitivity induced by down-regulation of microRNA-21 in gemcitabine-resistant pancreatic cancer cells by indole-3-carbinol. Anticancer Res. 33:1473–1481. 2013.PubMed/NCBI

86 

Shi GH, Ye DW, Yao XD, Zhang SL, Dai B, Zhang HL, Shen YJ, Zhu Y, Zhu YP, Xiao WJ, et al: Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells. Acta Pharmacol Sin. 31:867–873. 2010. View Article : Google Scholar : PubMed/NCBI

87 

Tomimaru Y, Eguchi H, Nagano H, Wada H, Tomokuni A, Kobayashi S, Marubashi S, Takeda Y, Tanemura M, Umeshita K, et al: MicroRNA-21 induces resistance to the anti-tumour effect of interferon-α/5-fluorouracil in hepatocellular carcinoma cells. Br J Cancer. 103:1617–1626. 2010. View Article : Google Scholar : PubMed/NCBI

88 

He C, Dong X, Zhai B, Jiang X, Dong D, Li B, Jiang H, Xu S and Sun X: miR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway. Oncotarget. 6:28867–28881. 2015.PubMed/NCBI

89 

Echevarría-Vargas IM, Valiyeva F and Vivas-Mejía PE: Upregulation of miR-21 in cisplatin resistant ovarian cancer via JNK-1/c-Jun pathway. PLoS One. 9:e970942014. View Article : Google Scholar : PubMed/NCBI

90 

Xie Z, Cao L and Zhang J: miR-21 modulates paclitaxel sensitivity and hypoxia-inducible factor-1α expression in human ovarian cancer cells. Oncol Lett. 6:795–800. 2013.PubMed/NCBI

91 

Lan F, Pan Q, Yu H and Yue X: Sulforaphane enhances temozolomide-induced apoptosis because of down-regulation of miR-21 via Wnt/β-catenin signaling in glioblastoma. J Neurochem. 134:811–818. 2015. View Article : Google Scholar : PubMed/NCBI

92 

Shi L, Chen J, Yang J, Pan T, Zhang S and Wang Z: miR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res. 1352:255–264. 2010. View Article : Google Scholar : PubMed/NCBI

93 

Zhou X, Ren Y, Liu A, Jin R, Jiang Q, Huang Y, Kong L, Wang X and Zhang L: WP1066 sensitizes oral squamous cell carcinoma cells to cisplatin by targeting STAT3/miR-21 axis. Sci Rep. 4:74612014. View Article : Google Scholar : PubMed/NCBI

94 

Bourguignon LY, Earle C, Wong G, Spevak CC and Krueger K: Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells. Oncogene. 31:149–160. 2012. View Article : Google Scholar : PubMed/NCBI

95 

Yang GD, Huang TJ, Peng LX, Yang CF, Liu RY, Huang HB, Chu QQ, Yang HJ, Huang JL, Zhu ZY, et al: Epstein-Barr Virus_Encoded LMP1 upregulates microRNA-21 to promote the resistance of nasopharyngeal carcinoma cells to cisplatin-induced Apoptosis by suppressing PDCD4 and Fas-L. PLoS One. 8:e783552013. View Article : Google Scholar : PubMed/NCBI

96 

Yang SM, Huang C, Li XF, Yu MZ, He Y and Li J: miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN. Toxicology. 306:162–168. 2013. View Article : Google Scholar : PubMed/NCBI

97 

Tao J, Lu Q, Wu D, Li P, Xu B, Qing W, Wang M, Zhang Z and Zhang W: microRNA-21 modulates cell proliferation and sensitivity to doxorubicin in bladder cancer cells. Oncol Rep. 25:1721–1729. 2011.PubMed/NCBI

Related Articles

Journal Cover

October 2016
Volume 5 Issue 4

Print ISSN: 2049-9434
Online ISSN:2049-9442

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Feng, Y., & Feng, Y. (2016). Emerging role of microRNA-21 in cancer (Review). Biomedical Reports, 5, 395-402. https://doi.org/10.3892/br.2016.747
MLA
Feng, Y., Tsao, C."Emerging role of microRNA-21 in cancer (Review)". Biomedical Reports 5.4 (2016): 395-402.
Chicago
Feng, Y., Tsao, C."Emerging role of microRNA-21 in cancer (Review)". Biomedical Reports 5, no. 4 (2016): 395-402. https://doi.org/10.3892/br.2016.747