Skip to main content
SpringerLink
Log in

The Role of miRNAs in Cisplatin-Resistant HeLa Cells

  • Conference paper
Bioinformatics Research and Applications (ISBRA 2015)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 9096))

Included in the following conference series:

Abstract

Chemotherapy is the main strategy in the treatment of cancer, however, the development of drug-resistance is the obstacle in long-term treatment of cervical cancer. Cisplatin is one of the most common drugs used in cancer therapy. Recently, accumulating evidence suggests that miRNAs are involved in various bioactivities in oncogenesis. It is not unexpected that miRNAs play a key role in acquiring of drug-resistance in the progression of tumor. In this study, we induced and maintained four levels of cisplatin-resistant HeLa cell lines (HeLa/CR1, HeLa/CR2, HeLa/CR3 and HeLa/CR4). According to the previous studies and exiting evidence, we selected five miRNAs (miR-183, miR-182, miR-30a, miR-15b and miR-16) and their potential target mRNAs as our research targets. The real-time RT-PCR was used to detect the relative expression of miRNAs and their mRNAs. The results show that miR-182 and miR-15b were up-regulated in resistant cell lines while miR-30a was significantly down-regulated. At the same time, the targets they regulated are related to the drug-resistance. The expression alteration of selected miRNAs in resistant cell lines compared to their parent HeLa cell line suggests that HeLa cell drug resistance is associated with distinct miRNAs, which indicates that miRNAs may be one of the therapy targets in the treatment of cervical cancer by sensitizing cell to chemotherapy.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Florea, A.M., Busselberg, D.: Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 3, 1351–1371 (2011)

    Article  Google Scholar 

  2. Cepeda, V., Fuertes, M.A., Castilla, J., Alonso, C., Quevedo, C., Pérez, J.M.: Biochemical mechanisms of cisplatin cytotoxicity. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 7(1), 3–18 (2007)

    Google Scholar 

  3. Calin, G.A., Sevignani, C., Dumitru, C.D., Hyslop, T., Noch, E., Yendamuri, S., Shimizu, M., Rattan, S., Bullrich, F., Negrini, M., Croce, C.M.: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences of the United States of America 101, 2999–3004 (2004)

    Article  Google Scholar 

  4. Saito, Y., Jones, P.M.: Epigenetic Activation of Tumor Suppressor MicroRNAs in Human Cancer Cells. Cell Cycle 5, 2220–2222 (2006)

    Article  Google Scholar 

  5. Sarkar, F.H., Li, Y., Wang, Z., Kong, D., Ali, S.: Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy 13, 57–66 (2010)

    Article  Google Scholar 

  6. Blower, P.E., Chung, J.H., Verducci, J.S., Lin, S., Park, J.K., Dai, Z., Liu, C.G., Schmittgen, T.D., Reinhold, W.C., Croce, C.M., Weinstein, J.N., Sadee, W.: MicroRNAs modulate the chemosensitivity of tumor cells. Molecular Cancer Therapeutics 7, 1–9 (2008)

    Article  Google Scholar 

  7. Zou, Z., Wu, L., Ding, H., Wang, Y., Zhang, Y., Chen, X., Chen, X., Zhang, C.Y., Zhang, Q., Zen, K.: MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing beclin 1-mediated autophagy. The Journal of Biological Chemistry 287, 4148–4156 (2012)

    Article  Google Scholar 

  8. Weller, M.: Predicting response to cancer chemotherapy: the role of p53. Cell and Tissue Research 292, 435–445 (1998)

    Article  Google Scholar 

  9. Minagawa, Y., Kigawa, J., Itamochi, H., Kanamori, Y., Shimada, M., Takahashi, M., Terakawa, N.: Cisplatin-resistant HeLa Cells Are Resistant to Apoptosis via p53-dependent and-independent Pathways. Cancer Science 90, 1373–1379 (1999)

    Google Scholar 

  10. Abate, G., Mshana, R.N., Miörner, H.: Evaluation of a colorimetric assay based on 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) for rapid detection of rifampicin resistance in Mycobacterium tuberculosis. The International Journal of Tuberculosis and Lung Disease 2, 1011–1016 (1998)

    Google Scholar 

  11. Cai, Z., Zhang, T., Wan, X.-F.: A Computational Framework for Influenza Antigenic Cartography. PLoS Comput Biol 6(10), e1000949 (2010)

    Google Scholar 

  12. Sorrentino, A., Liu, C.G., Addario, A., Peschle, C., Scambia, G., Ferlini, C.: Role of microRNAs in drug-resistant ovarian cancer cells. Gynecologic Oncology 111, 478–486 (2008)

    Article  Google Scholar 

  13. Reczko, M., Maragkakis, M., Alexiou, P., Grosse, I., Hatzigeorgiou, A.G.: Functional microRNA targets in protein coding sequences. Bioinformatics 28, 771–776 (2012)

    Article  Google Scholar 

  14. Paraskevopoulou, M.D., Georgakilas, G., Kostoulas, N., Vlachos, I.S., Vergoulis, T., Reczko, M., Filippidis, C., Dalamagas, T., Hatzigeorgiou, A.G.: DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows. Nucleic Acids Research 41, W169–W173 (2013)

    Google Scholar 

  15. Husted, S., Sokilde, R., Rask, L., Cirera, S., Busk, P.K., Eriksen, J., Litman, T.: MicroRNA expression profiles associated with development of drug resistance in Ehrlich ascites tumor cells. Molecular Pharmaceutics 8, 2055–2062 (2011)

    Article  Google Scholar 

  16. Sui, X., Chen, R., Wang, Z., Huang, Z., Kong, N., Zhang, M., Han, W., Lou, F., Yang, J., Zhang, Q., Wang, X., He, C., Pan, H.: Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment. Cell Death & Disease 4, e838 (2013)

    Google Scholar 

  17. Jami, M.S., Hou, J., Liu, M., Varney, M.L., Hassan, H., Dong, J., Ding, S.J.: Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness. BMC Cancer 14, 194 (2014)

    Article  Google Scholar 

  18. Birkenkamp-Demtroder, K., Maghnouj, A., Mansilla, F., Thorsen, K., Andersen, C.L., Oster, B., Hahn, S., Orntoft, T.F.: Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells. British Journal of Cancer 105, 552–561 (2011)

    Article  Google Scholar 

  19. Evensen, N.A., Kuscu, C., Nguyen, H.L., Zarrabi, K., Dufour, A., Kadam, P., Hu, Y.J., Pulkoski-Gross, A., Bahou, W.F., Zucker, S., Cao, J.: Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in cancer cell migration. Journal of the National Cancer Institute 105, 1402–1416 (2013)

    Article  Google Scholar 

  20. Kuscu, C.: Epigenetic Regulations and Promoter Characterization of CERIG (Cancer Endoplasmic Reticulum Gene-KIAA1199) (2012)

    Google Scholar 

  21. Shiota, M., Izumi, H., Tanimoto, A., Takahashi, M., Miyamoto, N., Kashiwagi, E., Kidani, A., Hirano, G., Masubuchi, D., Fukunaka, Y., Yasuniwa, Y., Naito, S., Nishizawa, S., Sasaguri, Y., Kohno, K.: Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth. Cancer Research 69, 3148–3156 (2009)

    Article  Google Scholar 

  22. Li, J., Fu, H., Xu, C., Tie, Y., Xing, R., Zhu, J., Qin, Y., Sun, Z., Zheng, X.: miR-183 inhibits TGF-beta1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells. BMC Cancer 10, 354 (2010)

    Article  Google Scholar 

  23. Ning, F.L., Wang, F., Li, M.L., Yu, Z.S., Hao, Y.Z., Chen, S.S.: MicroRNA-182 modulates chemosensitivity of human non-small cell lung cancer to cisplatin by targeting PDCD4. Diagn. Pathol. 9, 143 (2014)

    Article  Google Scholar 

  24. Wang, Y.Q., Guo, R.D., Guo, R.M., Sheng, W., Yin, L.R.: MicroRNA-182 promotes cell growth, invasion, and chemoresistance by targeting programmed cell death 4 (PDCD4) in human ovarian carcinomas. Journal of Cellular Biochemistry 114, 1464–1473 (2013)

    Article  Google Scholar 

  25. Tang, H., Bian, Y., Tu, C., Wang, Z., Yu, Z., Liu, Q., Xu, G., Wu, M., Li, G.: The miR-183/96/182 cluster regulates oxidative apoptosis and sensitizes cells to chemotherapy in gliomas. Current Cancer Drug Targets 13, 221–231 (2013)

    Article  Google Scholar 

  26. Wang, W.Q., Zhang, H., Wang, H.B., Sun, Y.G., Peng, Z.H., Zhou, G., Shi, M.Y., Wang, R.Q., Fang, D.C.: Programmed cell death 4 (PDCD4) enhances the sensitivity of gastric cancer cells to TRAIL-induced apoptosis by inhibiting the PI3K/Akt signaling pathway. Molecular Diagnosis & Therapy 14, 155–161 (2010)

    Article  Google Scholar 

  27. Wilson, M.S., Brosens, J.J., Schwenen, H.D., Lam, E.: FOXO and FOXM1 in cancer: the FOXO-FOXM1 axis shapes the outcome of cancer chemotherapy. Current Drug Targets 12, 1256–1266 (2011)

    Article  Google Scholar 

  28. Yang, A., Ma, J., Wu, M., Qin, W., Zhao, B., Shi, Y., Jin, Y., Xie, Y.: Aberrant microRNA-182 expression is associated with glucocorticoid resistance in lymphoblastic malignancies. Leukemia & Lymphoma 53, 2465–2473 (2012)

    Article  Google Scholar 

  29. Gong, C., Bauvy, C., Tonelli, G., Yue, W., Delomenie, C., Nicolas, V., Zhu, Y., Domergue, V., Marin-Esteban, V., Tharinger, H., Delbos, L., Gary-Gouy, H., Morel, A.P., Ghavami, S., Song, E., Codogno, P., Mehrpour, M.: Beclin 1 and autophagy are required for the tumorigenicity of breast cancer stem-like/progenitor cells. Oncogene 32, 2261–2272, 2272e 2261–2211 (2013)

    Google Scholar 

  30. Aredia, F., Scovassi, A.I.: Manipulation of autophagy in cancer cells: an innovative strategy to fight drug resistance. Future Medicinal Chemistry 5, 1009–1021 (2013)

    Article  Google Scholar 

  31. Kong, Y.W., Ferland-McCollough, D., Jackson, T.J., Bushell, M.: microRNAs in cancer management. The Lancet Oncology 13, e249–e258 (2012)

    Google Scholar 

  32. Kang, R., Zeh, H.J., Lotze, M.T., Tang, D.: The Beclin 1 network regulates autophagy and apoptosis. Cell Death and Differentiation 18, 571–580 (2011)

    Article  Google Scholar 

  33. Yu, Y., Yang, L., Zhao, M., Zhu, S., Kang, R., Vernon, P., Tang, D., Cao, L.: Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells. Leukemia 26, 1752–1760 (2012)

    Article  Google Scholar 

  34. Yang, J., Cao, Y., Sun, J., Zhang, Y.: Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells. Medical Oncology 27, 1114–1118 (2010)

    Article  Google Scholar 

  35. Aqeilan, R.I., Calin, G.A., Croce, C.M.: miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death and Differentiation 17, 215–220 (2010)

    Article  Google Scholar 

  36. Xia, L., Zhang, D., Du, R., Pan, Y., Zhao, L., Sun, S., Hong, L., Liu, J., Fan, D.: miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. International Journal of Cancer. Journal International du Cancer 123, 372–379 (2008)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Food Science and Engineering, Harbin Institute of Technology, Harbin, China

    Yubo Yang, Cuihong Dai, Aiju Hou, Dayou Cheng & Dechang Xu

  2. Department of Computer Science, Georgia State University, Atlanta, USA

    Zhipeng Cai

Authors
  1. Yubo Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cuihong Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhipeng Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aiju Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dayou Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dechang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Georgia State University, Atlanta, USA

    Robert Harrison

  2. Old Dominion University, Norfolk, USA

    Yaohang Li

  3. University of Connecticut, Storrs, Connecticut, USA

    Ion Măndoiu

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this paper

Cite this paper

Yang, Y., Dai, C., Cai, Z., Hou, A., Cheng, D., Xu, D. (2015). The Role of miRNAs in Cisplatin-Resistant HeLa Cells. In: Harrison, R., Li, Y., Măndoiu, I. (eds) Bioinformatics Research and Applications. ISBRA 2015. Lecture Notes in Computer Science(), vol 9096. Springer, Cham. https://doi.org/10.1007/978-3-319-19048-8_30

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-19048-8_30

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-19047-1

  • Online ISBN: 978-3-319-19048-8

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics

Search

Navigation