Skip to main content

Advertisement

SpringerLink
Log in

MicroRNA-127 is aberrantly downregulated and acted as a functional tumor suppressor in human pancreatic cancer

  • Original Article
  • Published:
Tumor Biology

Abstract

Pancreatic carcinoma is one of the most malignant human cancers. In this study, we intended to explore the molecular functional of microRNA-127 (miR-127) in regulating pancreatic cancer development both in vitro and in vivo. Quantitative real-time PCR (qRT-PCR) was performed to evaluate endogenous miR-127 expression in in vitro pancreatic cancer cell lines and in vivo clinical samples of pancreatic carcinoma. Lentiviral technology was applied to overexpress miR-127 in capan-1 and PANC-1 cells. Pancreatic cancer proliferation, cell-cycle progression, and invasion were assessed in vitro, and capan-1-derived tumorigenicity was evaluated in vivo. Dual-luciferase reporter assay and qRT-PCR were performed to assess the downstream target gene of miR-127 in pancreatic cancer, human Bcl-2-associated athanogene 5 (BAG5). BAG5 was subsequently upregulated in miR-127-overexpressed capan-1 and PANC-1 cells to evaluate its effect on pancreatic cancer progression. MiR-127 was preferentially downregulated in both pancreatic carcinoma cell lines and human pancreatic tumors. In lentivirus-infected capan-1 and PANC-1 cells, miR-127 overexpression significantly inhibited cancer progression, cell-cycle transition and invasion in vitro, as well as tumorigenicity in vivo. Human BAG5 was confirmed to be the downstream target of miR-127 in pancreatic cancer. Forced overexpression of BAG5 in capan-1 and PANC-1 cells reversed the tumor-suppressing effect of miR-127 on cancer development. MiR-127 is downregulated and acting as a tumor suppressor in pancreatic carcinoma. The functional regulation of miR-127 in pancreatic carcinoma is very likely through the inverse correlation of its downstream target gene of BAG5.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

    Article  PubMed  Google Scholar 

  2. Paulson AS, Tran Cao HS, Tempero MA, Lowy AM. Therapeutic advances in pancreatic cancer. Gastroenterology. 2013;144:1316–26.

    Article  CAS  PubMed  Google Scholar 

  3. Ansari D, Gustafsson A, Andersson R. Update on the management of pancreatic cancer: surgery is not enough. World J Gastroenterol. 2015;21:3157–65.

    PubMed  PubMed Central  Google Scholar 

  4. Mohammed S, Van Buren 2nd G, Fisher WE. Pancreatic cancer: advances in treatment. World J Gastroenterol. 2014;20:9354–60.

    PubMed  PubMed Central  Google Scholar 

  5. Puleo F, Marechal R, Demetter P, Bali MA, Calomme A, Closset J, Bachet JB, Deviere J, Van Laethem JL. New challenges in perioperative management of pancreatic cancer. World J Gastroenterol. 2015;21:2281–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Afonso-Grunz F, Muller S. Principles of miRNA-mRNA interactions: beyond sequence complementarity. Cell Mol Life Sci. 2015;72:3127–41.

    Article  CAS  PubMed  Google Scholar 

  7. Takasaki S. Roles of microRNAs in cancers and development. Methods Mol Biol. 2015;1218:375–413.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang R, B S. Small but influential: the role of microRNAs on gene regulatory network and 3′UTR evolution. J Genet Genomics. 2009;36:1–6.

    Article  PubMed  Google Scholar 

  9. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.

    Article  CAS  PubMed  Google Scholar 

  10. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  CAS  PubMed  Google Scholar 

  11. Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med. 2009;60:167–79.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302:1–12.

    Article  CAS  PubMed  Google Scholar 

  13. Lynam-Lennon N, Maher SG, Reynolds JV. The roles of microRNA in cancer and apoptosis. Biol Rev Camb Philos Soc. 2009;84:55–71.

    Article  PubMed  Google Scholar 

  14. Babashah S, Soleimani M. The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer. 2011;47:1127–37.

    Article  CAS  PubMed  Google Scholar 

  15. Gayral M, Jo S, Hanoun N, Vignolle-Vidoni A, Lulka H, Delpu Y, Meulle A, Dufresne M, Humeau M, Chalret du Rieu M, Bournet B, Selves J, Guimbaud R, Carrere N, Buscail L, Torrisani J, Cordelier P. MicroRNAs as emerging biomarkers and therapeutic targets for pancreatic cancer. World J Gastroenterol. 2014;20:11199–209.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Humeau M, Torrisani J, Cordelier P. miRNA in clinical practice: pancreatic cancer. Clin Biochem. 2013;46:933–6.

    Article  CAS  PubMed  Google Scholar 

  17. Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg. 2008;12:2171–6.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, Xiang D, Desano JT, Bommer GT, Fan D, Fearon ER, Lawrence TS, Xu L. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One. 2009;4:e6816.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Correa-Medina M, Bravo-Egana V, Rosero S, Ricordi C, Edlund H, Diez J, Pastori RL. MicroRNA miR-7 is preferentially expressed in endocrine cells of the developing and adult human pancreas. Gene Expr Patterns. 2009;9:193–9.

    Article  CAS  PubMed  Google Scholar 

  20. Yu J, Li A, Hong SM, Hruban RH, Goggins M. MicroRNA alterations of pancreatic intraepithelial neoplasias. Clin Cancer Res. 2012;18:981–92.

    Article  PubMed  Google Scholar 

  21. Doong H, Vrailas A, Kohn EC. What's in the ‘BAG’?—a functional domain analysis of the BAG-family proteins. Cancer Lett. 2002;188:25–32.

    Article  CAS  PubMed  Google Scholar 

  22. Bruchmann A, Roller C, Walther TV, Schafer G, Lehmusvaara S, Visakorpi T, Klocker H, Cato AC, Maddalo D. Bcl-2 associated athanogene 5 (Bag5) is overexpressed in prostate cancer and inhibits ER-stress induced apoptosis. BMC Cancer. 2013;13:96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lai XL, Huang YH, Li YS, Li GN, Wang LP, Sun R, Ma YS, Feng SY, Chang ZY, Wang XH, Fu D, Han X, Cong XL, Li WP. Differential expression profiling of microRNAs in para-carcinoma, carcinoma and relapse human pancreatic cancer. Clin Transl Oncol. 2015;17:398–408.

    Article  CAS  PubMed  Google Scholar 

  24. Chen J, Wang M, Guo M, Xie Y, Cong YS. miR-127 regulates cell proliferation and senescence by targeting BCL6. PLoS One. 2013;8:e80266.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Guo LH, Li H, Wang F, Yu J, He JS. The tumor suppressor roles of miR-433 and miR-127 in gastric cancer. Int J Mol Sci. 2013;14:14171–84.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ying Z, Haiyan G, Haidong G. BAG5 regulates PTEN stability in MCF-7 cell line. BMB Rep. 2013;46:490–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

This work is supported by Grants from the National Natural Science Foundation of China (No.30872510, 81272534, 81260349, 81370569); and the Natural Science Foundation of Songjiang District (No.15SJGG23) and Key Program of Medical Specialty Construction in Shanghai City (ZK2015B20).

Author information

Authors and Affiliations

  1. Department of General Surgery, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, China

    Yuan Yu

  2. Department of Gastroenterology Surgery, Songjiang Hospital Affiliated to The First People’s Hospital of Shanghai Jiaotong University, 648 Middle Zhongshan Rd, Shanghai, 201600, China

    Lei Liu, Ruirui Ma, Haibing Gong & Congjun Wang

  3. Department of Gastroenterology, Songjiang Hospital Affiliated to The First People’s Hospital of Shanghai Jiaotong University, 648 Middle Zhongshan Rd, Shanghai, 201600, China

    Ping Xu

Authors
  1. Yuan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruirui Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haibing Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ping Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Congjun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ping Xu or Congjun Wang.

Ethics declarations

Ethical approval

Ethical approval for this study was granted by the Clinical Research and Ethic Committee at the Fifth People’s Hospital of Shanghai and Songjiang Hospital Affiliated to The First People’s Hospital of Shanghai Jiaotong University in Shanghai, China. Consent forms were signed by all participating patients. All protocols were performed in accordance with the Declaration of Helsinki and the guidelines for good clinical practice in China.

Conflicts of interest

None

Additional information

Yuan Yu and Lei Liu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Y., Liu, L., Ma, R. et al. MicroRNA-127 is aberrantly downregulated and acted as a functional tumor suppressor in human pancreatic cancer. Tumor Biol. 37, 14249–14257 (2016). https://doi.org/10.1007/s13277-016-5270-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5270-0

Keywords

Search

Navigation