Tumor Biology

, Volume 36, Issue 8, pp 5825–5830 | Cite as

MicroRNA-335 represents an independent prognostic marker in cervical cancer

  • Changhe Wang
  • Tao Jiang
Research Article


Advanced stages with distant metastases or recurrence lack reliable prognostic predictor for cervical cancer. Therefore, the purpose of this study was to investigate the clinical significance of miR-335 expression in cervical cancer. A total of 138 cervical cancer samples were collected, and normal cervical tissues were obtained as matched-pair controls. The level of miR-335 expression was examined using quantitative real-time polymerase chain reaction. Overall survival was analyzed using Kaplan–Meier method. Moreover, the relationship between the expression of miR-335 and the clinicopathological features was further analyzed using Cox regression. Lower miR-335 expression was found in cervical cancer specimens. Cervical cancer patients with reduced miR-335 level had shorter survival time, compared with those with high levels of miR-335 expression (P = 0.011, log-rank = 6.458). Through Cox regression, we found that miR-335 expression was associated with the survival of cervical cancer (RR = 0.251, 95 % CI 0.095–0.663, P = 0.005). The results suggested that miR-335 expression was decreased in cervical cancer specimens and lower miR-335 expression resulted in poorer survival in patients with cervical cancer. Our findings indicated that miR-335 may be a candidate factor for predicting prognosis for cervical cancer.


MicroRNA-335 Prognosis Cervical cancer Expression 


Conflicts of interest





  1. 1.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMedGoogle Scholar
  2. 2.
    Wei LH. Prevention and treatment of cervical cancer, it is a long-term and arduous task. Zhonghua Fu Chan Ke Za Zhi. 2013;48:304–6.PubMedGoogle Scholar
  3. 3.
    Huang EY, Hsu HC, Sun LM, Chanchien CC, Lin H, et al. Prognostic value of pretreatment carcinoembryonic antigen after definitive radiotherapy with or without concurrent chemotherapy for squamous cell carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys. 2011;81:1105–13.CrossRefPubMedGoogle Scholar
  4. 4.
    Tsai CC, Liu YS, Huang EY, Huang SC, Chang HW, et al. Value of preoperative serum CA125 in early-stage adenocarcinoma of the uterine cervix without pelvic lymph node metastasis. Gynecol Oncol. 2006;100:591–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Tsai CC, Lin H, Huang EY, Huang SC, Hsieh CH, et al. The role of the preoperative serum carcinoembryonic antigen level in early-stage adenocarcinoma of the uterine cervix. Gynecol Oncol. 2004;94:363–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Hacker NF, Nieberg RK, Berek JS, Leuchter RS, Lucas WE, et al. Superficially invasive vulvar cancer with nodal metastases. Gynecol Oncol. 1983;15:65–77.CrossRefPubMedGoogle Scholar
  7. 7.
    Pickel H, Haas J, Lahousen M. Prognostic factors in cervical cancer. Eur J Obstet Gynecol Reprod Biol. 1997;71:209–13.CrossRefPubMedGoogle Scholar
  8. 8.
    Jin L, Shen Q, Ding S, Jiang W, Jiang L, et al. Immunohistochemical expression of Annexin A2 and S100A proteins in patients with bulky stage IB-IIA cervical cancer treated with neoadjuvant chemotherapy. Gynecol Oncol. 2012;126:140–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Li Z, Yu CP, Zhong Y, Liu TJ, Huang QD, et al. Sam68 expression and cytoplasmic localization is correlated with lymph node metastasis as well as prognosis in patients with early-stage cervical cancer. Ann Oncol. 2012;23:638–46.CrossRefPubMedGoogle Scholar
  10. 10.
    Song C, Zhu S, Wu C, Kang J. Histone deacetylase (HDAC) 10 suppresses cervical cancer metastasis through inhibition of matrix metalloproteinase (MMP) 2 and 9 expression. J Biol Chem. 2013;288:28021–33.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.CrossRefPubMedGoogle Scholar
  12. 12.
    Ronchetti D, Lionetti M, Mosca L, Agnelli L, Andronache A, et al. An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma. BMC Med Genomics. 2008;1:37.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Shu M, Zhou Y, Zhu W, Zhang H, Wu S, et al. MicroRNA 335 is required for differentiation of malignant glioma cells induced by activation of cAMP/protein kinase A pathway. Mol Pharmacol. 2012;81:292–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Shi L, Jiang D, Sun G, Wan Y, Zhang S, et al. miR-335 promotes cell proliferation by directly targeting Rb1 in meningiomas. J Neuro-Oncol. 2012;110:155–62.CrossRefGoogle Scholar
  15. 15.
    Huang HY, Cheng YY, Liao WC, Tien YW, Yang CH, et al. SOX4 transcriptionally regulates multiple SEMA3/plexin family members and promotes tumor growth in pancreatic cancer. PLoS One. 2012;7:e48637.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Heyn H, Engelmann M, Schreek S, Ahrens P, Lehmann U, et al. MicroRNA miR-335 is crucial for the BRCA1 regulatory cascade in breast cancer development. Int J Cancer. 2011;129:2797–806.CrossRefPubMedGoogle Scholar
  17. 17.
    Dohi O, Yasui K, Gen Y, Takada H, Endo M, et al. Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. Int J Oncol. 2013;42:411–8.PubMedGoogle Scholar
  18. 18.
    Cao J, Cai J, Huang D, Han Q, Chen Y, et al. miR-335 represents an independent prognostic marker in epithelial ovarian cancer. Am J Clin Pathol. 2014;141:437–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Yan Z, Xiong Y, Xu W, Gao J, Cheng Y, et al. Identification of hsa-miR-335 as a prognostic signature in gastric cancer. PLoS One. 2012;7:e40037.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Xu Y, Zhao F, Wang Z, Song Y, Luo Y, et al. MicroRNA-335 acts as a metastasis suppressor in gastric cancer by targeting Bcl-w and specificity protein 1. Oncogene. 2012;31:1398–407.CrossRefPubMedGoogle Scholar
  21. 21.
    Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12:861–74.CrossRefPubMedGoogle Scholar
  22. 22.
    Jiang W, Chen X, Liao M, Li W, Lian B, et al. Identification of links between small molecules and miRNAs in human cancers based on transcriptional responses. Sci Rep. 2012;2:282.PubMedPubMedCentralGoogle Scholar
  23. 23.
    He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.CrossRefPubMedGoogle Scholar
  24. 24.
    Babashah S, Soleimani M. The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer. 2011;47:1127–37.CrossRefPubMedGoogle Scholar
  25. 25.
    Christensen BC, Moyer BJ, Avissar M, Ouellet LG, Plaza SL, et al. A let-7 microRNA-binding site polymorphism in the KRAS 3’ UTR is associated with reduced survival in oral cancers. Carcinogenesis. 2009;30:1003–7.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72:397–402.CrossRefPubMedGoogle Scholar
  27. 27.
    Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.CrossRefPubMedGoogle Scholar
  28. 28.
    Peng HH, Zhang YD, Gong LS, Liu WD, Zhang Y. Increased expression of microRNA-335 predicts a favorable prognosis in primary gallbladder carcinoma. Onco Targets Ther. 2013;6:1625–30.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Ma J, Li N, Guarnera M, Jiang F. Quantification of plasma miRNAs by digital PCR for cancer diagnosis. Biomark Insights. 2013;8:127–36.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Yang H, Zhang C, Lu YX, Wu XJ, Yuan L, et al. Construction of has-miR-335 lentiviral vector and verification of the target gene of miR-335. Nan Fang Yi Ke Da Xue Xue Bao. 2012;32:306–11.PubMedGoogle Scholar
  31. 31.
    Tome M, Lopez-Romero P, Albo C, Sepulveda JC, Fernandez-Gutierrez B, et al. miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ. 2011;18:985–95.CrossRefPubMedGoogle Scholar
  32. 32.
    Lynch J, Fay J, Meehan M, Bryan K, Watters KM, et al. MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-beta signalling pathway. Carcinogenesis. 2012;33:976–85.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Jiang J, Sun X, Wang W, Jin X, Bo X, et al. Tumor microRNA-335 expression is associated with poor prognosis in human glioma. Med Oncol. 2012;29:3472–7.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of GynecologyJining No.1 People’s HospitalJiningChina

Personalised recommendations