Skip to main content

Advertisement

Log in

Combined downregulation of microRNA-133a and microRNA-133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

microRNA-133a (miR-133a) and miR-133b, located on chromosome 18 in the same bicistronic unit, have been commonly identified as being downregulated in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the correlation of miR-133a/b expression with efficacy of paclitaxel-based chemotherapy and clinical outcome of ESCC patients. miR-133a expression and miR-133b expression were examined in 100 newly diagnosed ESCC patients prior to treatment by quantitative real-time PCR. Then, the patients received four cycles of paclitaxel-based chemotherapy, the short-term treatment efficacy was evaluated, and a 3-year follow-up was performed. Expression levels of miR-133a and miR-133b were both significantly lower in ESCC tissues compared to adjacent noncancerous tissues (both P < 0.001). In addition, combined miR-133a/b downregulation was found to be closely correlated with advanced tumor stage (P = 0.02) and poor differentiation (P = 0.01). Moreover, the response rate of ESCC patients to paclitaxel-based chemotherapy was significantly higher in combined miR-133a/b downregulation group compared with other groups (P = 0.02). Furthermore, univariate and multivariate Cox analyses revealed that tumor stage and combined expression of miR-133a/b were independent prognosis factors in ESCC patients. Our data offer the convincing evidence that combined expression of miR-133a and miR-133b may predict chemosensitivity of patients with ESCC undergoing paclitaxel-based chemotherapy, implying its importance in applying ‘personalized cancer medicine’ in the clinical treatment of ESCC. We also identified combined expression of miR-133a and miR-133b as an effective prognostic marker of this malignancy.

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

Similar content being viewed by others

References

  1. Uemura N, Kondo T. Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer. World J Gastrointest Pathophysiol. 2014;5:322–34.

    PubMed  PubMed Central  Google Scholar 

  2. D’Journo XB, Thomas PA. Current management of esophageal cancer. J Thorac Dis. 2014;6(Suppl 2):S253–64.

    PubMed  PubMed Central  Google Scholar 

  3. Nakajima M, Kato H. Treatment options for esophageal squamous cell carcinoma. Expert Opin Pharmacother. 2013;14:1345–54.

    Article  PubMed  CAS  Google Scholar 

  4. Baba Y, Watanabe M, Yoshida N, Baba H. Neoadjuvant treatment for esophageal squamous cell carcinoma. World J Gastrointest Oncol. 2014;6:121–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Xu Y, Yu X, Chen Q, Mao W. Neoadjuvant versus adjuvant treatment: which one is better for resectable esophageal squamous cell carcinoma? World J Surg Oncol. 2012;10:173.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Lehrbach DM, Nita ME, Cecconello I. Molecular aspects of esophageal squamous cell carcinoma carcinogenesis. Arq Gastroenterol. 2003;40:256–61.

    Article  PubMed  Google Scholar 

  7. van Rooij E, Kauppinen S. Development of microRNA therapeutics is coming of age. EMBO Mol Med. 2014;6:851–64.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cipollini M, Landi S, Gemignani F. MicroRNA binding site polymorphisms as biomarkers in cancer management and research. Pharmgenomics Pers Med. 2014;7:173–91.

    PubMed  PubMed Central  Google Scholar 

  9. Wahid F, Khan T, Kim YY. MicroRNA and diseases: therapeutic potential as new generation of drugs. Biochimie. 2014;104C:12–26.

    Article  Google Scholar 

  10. Chen D, Cabay RJ, Jin Y, Wang A, Lu Y, Shah-Khan M, Zhou X. MicroRNA deregulations in head and neck squamous cell carcinomas. J Oral Maxillofac Res. 2013;4:e2.

    PubMed  PubMed Central  Google Scholar 

  11. Wang Y, Wang Q, Zhang N, Ma H, Gu Y, Tang H, Xu Z, Gao Y. Identification of microRNAs as novel biomarkers for detecting esophageal squamous cell carcinoma in Asians: a meta-analysis. Tumour Biol. 2014 In press.

  12. Chen Z, Li J, Tian L, Zhou C, Gao Y, Zhou F, Shi S, Feng X, Sun N, Yao R, Shao K, Li N, Qiu B, Tan F, He J. MiRNA expression profile reveals a prognostic signature for esophageal squamous cell carcinoma. Cancer Lett. 2014;350:34–42.

    Article  PubMed  CAS  Google Scholar 

  13. Lu J, Lu N, Xue L, Jin M. Different expression of miRNAs in early esophageal squamous cell carcinoma with differential prognosis. Dis Esophagus. 2014 In press.

  14. Yu H, Lu Y, Li Z, Wang Q. microRNA-133: expression, function and therapeutic potential in muscle diseases and cancer. Curr Drug Targets. 2014;15:817–28.

    Article  PubMed  CAS  Google Scholar 

  15. Feng Y, Niu LL, Wei W, Zhang WY, Li XY, Cao JH, Zhao SH. A feedback circuit between miR-133 and the ERK1/2 pathway involving an exquisite mechanism for regulating myoblast proliferation and differentiation. Cell Death Dis. 2013;4:e934.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Zhou Y, Wu D, Tao J, Qu P, Zhou Z, Hou J. MicroRNA-133 inhibits cell proliferation, migration and invasion by targeting epidermal growth factor receptor and its downstream effector proteins in bladder cancer. Scand J Urol. 2013;47:423–32.

    Article  PubMed  CAS  Google Scholar 

  17. Nohata N, Hanazawa T, Enokida H, Seki N. microRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. Oncotarget. 2012;3:9–21.

    PubMed  PubMed Central  Google Scholar 

  18. Wang LL, Du LT, Li J, Liu YM, Qu AL, Yang YM, Zhang X, Zheng GX, Wang CX. Decreased expression of miR-133a correlates with poor prognosis in colorectal cancer patients. World J Gastroenterol. 2014;20:11340–6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Luo J, Zhou J, Cheng Q, Zhou C, Ding Z. Role of microRNA-133a in epithelial ovarian cancer pathogenesis and progression. Oncol Lett. 2014;7:1043–8.

    PubMed  CAS  PubMed Central  Google Scholar 

  20. Wang LK, Hsiao TH, Hong TM, Chen HY, Kao SH, Wang WL, Yu SL, Lin CW, Yang PC. MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma. PLoS ONE. 2014;9:e96765.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Xiang KM, Li XR. MiR-133b acts as a tumor suppressor and negatively regulates TBPL1 in colorectal cancer cells. Asian Pac J Cancer Prev. 2014;15:3767–72.

    Article  PubMed  Google Scholar 

  22. Karatas OF, Guzel E, Suer I, Ekici ID, Caskurlu T, Creighton CJ, Ittmann M, Ozen M. miR-1 and miR-133b are differentially expressed in patients with recurrent prostate cancer. PLoS ONE. 2014;9:e98675.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zhao H, Li M, Li L, Yang X, Lan G, Zhang Y. MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis. PLoS ONE. 2013;8:e83571.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Cristobal I, Madoz-Gurpide J, Martin-Aparicio E, Carames C, Aguilera O, Rojo F, Garcia-Foncillas J. The tumour suppressor miR-133b is markedly downregulated in liver metastatic colorectal cancer. Br J Cancer. 2014 In press.

  25. Qin W, Dong P, Ma C, Mitchelson K, Deng T, Zhang L, Sun Y, Feng X, Ding Y, Lu X, He J, Wen H, Cheng J. MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways. Oncogene. 2012;31:4067–75.

    Article  PubMed  CAS  Google Scholar 

  26. Zhao Y, Huang J, Zhang L, Qu Y, Li J, Yu B, Yan M, Yu Y, Liu B, Zhu Z. MiR-133b is frequently decreased in gastric cancer and its overexpression reduces the metastatic potential of gastric cancer cells. BMC Cancer. 2014;14:34.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Zhang C, Wang C, Chen X, Yang C, Li K, Wang J, Dai J, Hu Z, Zhou X, Chen L, Zhang Y, Li Y, Qiu H, Xing J, Liang Z, Ren B, Yang C, Zen K, Zhang CY. Expression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinoma. Clin Chem. 2010;56:1871–9.

    Article  PubMed  CAS  Google Scholar 

  28. Suzuki S, Yokobori T, Tanaka N, Sakai M, Sano A, Inose T, Sohda M, Nakajima M, Miyazaki T, Kato H, Kuwano H. CD47 expression regulated by the miR-133a tumor suppressor is a novel prognostic marker in esophageal squamous cell carcinoma. Oncol Rep. 2012;28:465–72.

    PubMed  CAS  Google Scholar 

  29. Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, Chiyomaru T, Enokida H, Nakagawa M, Matsubara H. miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int J Cancer. 2010;127:2804–14.

    Article  PubMed  CAS  Google Scholar 

  30. Fu HL, de Wu P, Wang XF, Wang JG, Jiao F, Song LL, Xie H, Wen XY, Shan HS, Du YX, Zhao YP. Altered miRNA expression is associated with differentiation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) in patients from Huaian, China. Cell Biochem Biophys. 2013;67:657–68.

    Article  PubMed  CAS  Google Scholar 

  31. Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N, Fuse M, Ichikawa T, Naya Y, Nakagawa M, Seki N. Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2012;106:405–13.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Moriya Y, Nohata N, Kinoshita T, Mutallip M, Okamoto T, Yoshida S, Suzuki M, Yoshino I, Seki N. Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma. J Hum Genet. 2012;57:38–45.

    Article  PubMed  CAS  Google Scholar 

  33. Kinoshita T, Nohata N, Fuse M, Hanazawa T, Kikkawa N, Fujimura L, Watanabe-Takano H, Yamada Y, Yoshino H, Enokida H, Nakagawa M, Okamoto Y, Seki N. Tumor suppressive microRNA-133a regulates novel targets: moesin contributes to cancer cell proliferation and invasion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun. 2012;418:378–83.

    Article  PubMed  CAS  Google Scholar 

  34. Hsu FM, Lin CC, Lee JM, Chang YL, Hsu CH, Tsai YC, Lee YC, Cheng JC. Improved local control by surgery and paclitaxel-based chemoradiation for esophageal squamous cell carcinoma: results of a retrospective non-randomized study. J Surg Oncol. 2008;98:34–41.

    Article  PubMed  Google Scholar 

  35. Chen WW, Lin CC, Huang TC, Cheng AL, Yeh KH, Hsu CH. Prognostic factors of metastatic or recurrent esophageal squamous cell carcinoma in patients receiving three-drug combination chemotherapy. Anticancer Res. 2013;33:4123–8.

    PubMed  CAS  Google Scholar 

  36. Huang JX, Shen SL, Lin M, Xiao W, Chen WC, Lin MS, Yu H, Chen P, Qian RY. Cyclin A overexpression is associated with chemosensitivity to paclitaxel-based chemotherapy in patients with esophageal squamous cell carcinoma. Oncol Lett. 2012;4:607–11.

    PubMed  CAS  PubMed Central  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wanwei Wang.

Additional information

Guiming Chen and Jin Peng have contributed equally in this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, G., Peng, J., Zhu, W. et al. Combined downregulation of microRNA-133a and microRNA-133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy. Med Oncol 31, 263 (2014). https://doi.org/10.1007/s12032-014-0263-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0263-6

Keywords

Navigation