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Increased expression of miR-15b is associated with clinicopathological features and poor prognosis in cervical carcinoma

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

The aims of this study were to explore the expression of microRNA-15b (miR-15b) in cervical carcinoma and to correlate its expression with clinicopathological characteristics and prognosis.

Methods

Quantitative reverse transcriptase polymerase chain reaction analysis was conducted to quantify the expression level of miR-15b in 607 cervical tissues, including 185 cervical carcinoma tissues, 124 CIN I lesions, 148 CIN II-III lesions, and 150 normal cervical tissues. The 5-year overall cumulative survival rates for all patients with cervical carcinoma were calculated using Kaplan–Meier survival analysis, and multivariate survival analysis of these patients was completed using the stepwise Cox proportional hazards regression model.

Results

The expression of miR-15b gradually increased from normal cervical tissues to CIN lesions and then to cervical carcinoma tissues (all P < 0.05), and it was strongly correlated with degree of differentiation, clinical stage, tumor diameter, and lymph-node metastases (all P < 0.05). When the median value of miR-15b expression was used as the cut-off point, patients with high miR-15b expression (above the median) had worse 5-year overall cumulative survival rates than those who exhibited low miR-15b expression (below the median; P < 0.05). Multivariate analysis using the Cox regression model identified miR-15b expression, clinical stage, tumor diameter, and lymph-node metastasis as independent risk factors for cervical carcinoma prognosis (all P < 0.05).

Conclusion

Our results indicate that elevated miRNA-15b expression is a typical feature in cervical carcinoma, which could be a useful clinical predictor for the early diagnosis and evaluation of cervical carcinoma prognosis.

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References

  1. Liu JH, Xi P, Chai YL, Wang J, Wang T, Liu Z, Dai PG (2016) Association of DNA repair gene polymorphisms with response to cisplatin-based concurrent chemoradiotherapy in patients with cervical carcinoma. DNA Repair (Amst) 41:69–72

    Article  CAS  Google Scholar 

  2. Zhang L, Qian H, Sha M, Luan Z, Lin M, Yuan D, Li X, Huang J, Ye L (2016) Downregulation of HOTAIR Expression Mediated Anti-Metastatic Effect of Artesunate on Cervical Cancer by Inhibiting COX-2 Expression. PLoS One 11:e0164838

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sandoval-Basilio J, Serafin-Higuera N, Reyes-Hernandez OD, Serafin-Higuera I, Leija-Montoya G, Blanco-Morales M, Sierra-Martinez M, Ramos-Mondragon R, Garcia S, Lopez-Hernandez LB, Yocupicio-Monroy M, Alcaraz-Estrada SL (2016) Low proteolytic clipping of histone H3 in cervical cancer. J Cancer 7:1856–1860

    Article  PubMed  PubMed Central  Google Scholar 

  4. Liu P, Xin F, Ma CF (2015) Clinical significance of serum miR-196a in cervical intraepithelial neoplasia and cervical cancer. Genet Mol Res 14:17995–18002

    Article  CAS  PubMed  Google Scholar 

  5. Yu JQ, Zhou Q, Zheng YF, Bao Y (2015) Expression of vimentin and Ki-67 proteins in cervical squamous cell carcinoma and their relationships with clinicopathological features. Asian Pac J Cancer Prev 16:4271–4275

    Article  PubMed  Google Scholar 

  6. Cho U, Kim HM, Park HS, Kwon OJ, Lee A, Jeong SW (2016) Nuclear expression of GS28 protein: a novel biomarker that predicts worse prognosis in cervical cancers. PLoS One 11:e0162623

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lin Y, Wu J, Chen H, Mao Y, Liu Y, Mao Q, Yang K, Zheng X, Xie L (2012) Cyclin-dependent kinase 4 is a novel target in micoRNA-195-mediated cell cycle arrest in bladder cancer cells. FEBS Lett 586:442–447

    Article  CAS  PubMed  Google Scholar 

  8. Liu ZL, Wang H, Liu J, Wang ZX (2013) 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

    Article  CAS  PubMed  Google Scholar 

  9. Xiao H, Zeng J, Li H, Chen K, Yu G, Hu J, Tang K, Zhou H, Huang Q, Li A, Li Y, Ye Z, Wang J, Xu H (2015) MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis. Oncotarget 6:13201–13215

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chen X, Zhao G, Wang F, Gao F, Luo H, Wang Y, Du Y, Chen X, Xue C, Dong Z, Song G (2014) Upregulation of miR-513b inhibits cell proliferation, migration, and promotes apoptosis by targeting high mobility group-box 3 protein in gastric cancer. Tumour Biol 35:11081–11089

    Article  CAS  PubMed  Google Scholar 

  11. Li S, Qin X, Li Y, Zhang X, Niu R, Zhang H, Cui A, An W, Wang X (2015) MiR-133a suppresses the migration and invasion of esophageal cancer cells by targeting the EMT regulator SOX4. Am J Transl Res 7:1390–1403

    PubMed  PubMed Central  Google Scholar 

  12. Zhang Y, Huang F, Wang J, Peng L, Luo H (2015) MiR-15b mediates liver cancer cells proliferation through targeting BCL-2. Int J Clin Exp Pathol 8:15677–15683

    PubMed  PubMed Central  Google Scholar 

  13. Li J, Chen Y, Guo X, Zhou L, Jia Z, Tang Y, Lin L, Liu W, Ren C (2016) Inhibition of miR-15b decreases cell migration and metastasis in colorectal cancer. Tumour Biol 37:8765–8773

    Article  CAS  PubMed  Google Scholar 

  14. Ji WB, Liu X, Luo Y, Zhang WZ (2016) High expression of miR-15b predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy. Oncol Rep 36:1901–1908

    CAS  PubMed  Google Scholar 

  15. MacLean JA 2nd, King ML, Okuda H, Hayashi K (2016) WNT7A regulation by miR-15b in ovarian cancer. PLoS One 11:e0156109

    Article  PubMed  PubMed Central  Google Scholar 

  16. Guan Y, Guo L, Zukerberg L, Rueda BR, Styer AK (2016) MicroRNA-15b regulates reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression in human uterine leiomyoma. Reprod Biol Endocrinol 14:45

    Article  PubMed  PubMed Central  Google Scholar 

  17. Myklebust MP, Bruland O, Fluge O, Skarstein A, Balteskard L, Dahl O (2011) MicroRNA-15b is induced with E2F-controlled genes in HPV-related cancer. Br J Cancer 105:1719–1725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Arakawa F, Kimura Y, Yoshida N, Miyoshi H, Doi A, Yasuda K, Nakajima K, Kiyasu J, Niino D, Sugita Y, Tashiro K, Kuhara S, Seto M, Ohshima K (2016) Identification of miR-15b as a transformation-related factor in mantle cell lymphoma. Int J Oncol 48:485–492

    CAS  PubMed  Google Scholar 

  19. Sun G, Yan S, Shi L, Wan Z, Jiang N, Li M, Guo J (2015) Decreased expression of miR-15b in human gliomas is associated with poor prognosis. Cancer Biother Radiopharm 30:169–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu LF, Liang Z, Lv ZR, Liu XH, Bai J, Chen J, Chen C, Wang Y (2012) MicroRNA-15a/b are up-regulated in response to myocardial ischemia/reperfusion injury. J Geriatr Cardiol 9:28–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM (2008) Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One 3:e2557

    Article  PubMed  PubMed Central  Google Scholar 

  22. M PN (2014) World medical association publishes the revised declaration of helsinki. Natl Med J India 27:56

    PubMed  Google Scholar 

  23. Pecorelli S, Zigliani L, Odicino F (2009) Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet 105:107–108

    Article  PubMed  Google Scholar 

  24. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  25. Liu J, Yang L, Zhang J, Zhang J, Chen Y, Li K, Li Y, Li Y, Yao L, Guo G (2012) Knock-down of NDRG2 sensitizes cervical cancer Hela cells to cisplatin through suppressing Bcl-2 expression. BMC Cancer 12:370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kedmi M, Ben-Chetrit N, Korner C, Mancini M, Ben-Moshe NB, Lauriola M, Lavi S, Biagioni F, Carvalho S, Cohen-Dvashi H, Schmitt F, Wiemann S, Blandino G, Yarden Y (2015) EGF induces microRNAs that target suppressors of cell migration: miR-15b targets MTSS1 in breast cancer. Sci Signal 8:ra29

    Article  PubMed  Google Scholar 

  27. Cardeal LB, Boccardo E, Termini L, Rabachini T, Andreoli MA, di Loreto C, Longatto Filho A, Villa LL, Maria-Engler SS (2012) HPV16 oncoproteins induce MMPs/RECK-TIMP-2 imbalance in primary keratinocytes: possible implications in cervical carcinogenesis. PLoS One 7:e33585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Frampton AE, Krell J, Gall TM, Castellano L, Stebbing J, Jiao LR (2015) miR-15b and miR-17 are tumor-derived plasma micrornas dysregulated in colorectal neoplasia. Ann Surg 262:e61–e62

    Article  PubMed  Google Scholar 

  29. Gomez-Gomez Y, Organista-Nava J, Gariglio P (2013) Deregulation of the miRNAs expression in cervical cancer: human papillomavirus implications. Biomed Res Int 2013:407052

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shen HW, Tan JF, Shang JH, Hou MZ, Liu J, He L, Yao SZ, He SY (2016) CPE overexpression is correlated with pelvic lymph node metastasis and poor prognosis in patients with early-stage cervical cancer. Arch Gynecol Obstet 294:333–342

    Article  CAS  PubMed  Google Scholar 

  31. Khalil J, Bellefqih S, Afif M, Elkacemi H, Kebdani T, Benjaafar N (2015) Prognostic factors affecting cervical adenocarcinoma: 10 years experience in a single institution. Arch Gynecol Obstet 292:915–921

    Article  CAS  PubMed  Google Scholar 

  32. Finnerty JR, Wang WX, Hebert SS, Wilfred BR, Mao G, Nelson PT (2010) The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases. J Mol Biol 402:491–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank for all the people for their help with editing the manuscript.

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Authors and Affiliations

  1. Department of Gynecology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, No. 60, Jingzhong Road, Jingzhou District, Jingzhou, 434020, Hubei, People’s Republic of China

    Fang Wen, Jia-Zhen Xu & Xian-Rong Wang

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  1. Fang Wen
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Correspondence to Xian-Rong Wang.

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There are no conflicts of interests regarding the publication of this paper.

Ethical approval

The presented study received the ethical approval of the Ethics Committee of the Jingzhou Central Hospital. All participants signed informed consent before the beginning of the research. This study conformed to the standards of the Declaration of Helsinki.

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Wen, F., Xu, JZ. & Wang, XR. Increased expression of miR-15b is associated with clinicopathological features and poor prognosis in cervical carcinoma. Arch Gynecol Obstet 295, 743–749 (2017). https://doi.org/10.1007/s00404-016-4286-4

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  • DOI: https://doi.org/10.1007/s00404-016-4286-4

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