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Article

Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel

  • Authors:
    • Ning Chen
    • Hye Sook Chon
    • Yin Xiong
    • Douglas C. Marchion
    • Patricia L. Judson
    • Ardeshir Hakam
    • Jesus Gonzalez-Bosquet
    • Jennifer Permuth-Wey
    • Robert M. Wenham
    • Sachin M. Apte
    • Jin Q. Cheng
    • Thomas A. Sellers
    • Johnathan M. Lancaster
  • View Affiliations / Copyright

    Affiliations: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
  • Pages: 376-383
    |
    Published online on: November 13, 2013
       https://doi.org/10.3892/or.2013.2847
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Abstract

Paclitaxel is a mainstay of treatment for many solid tumors, and frequently, clinical outcome is influenced by paclitaxel sensitivity. Despite this, our understanding of the molecular basis of paclitaxel response is incomplete. Recently, it has been shown that microRNAs (miRNAs) influence messenger RNA (mRNA) transcriptional control and can contribute to human carcinogenesis. In the present study, our objective was to identify miRNAs associated with cancer cell line response to paclitaxel and to evaluate these miRNAs as therapeutic targets to increase paclitaxel sensitivity. We measured the expression of 335 unique miRNAs in 40 human cancer cell lines selected from the NCI panel. We then integrated miRNA expression data with publicly available paclitaxel-sensitivity (GI50) data for each of the 40 cell lines to identify miRNAs associated with paclitaxel sensitivity. Ovarian cancer cell lines with differential miRNA expression and paclitaxel sensitivity were transiently transfected with miRNA precursors and inhibitors, and the effects on in vitro cell paclitaxel sensitivity were evaluated. Pearson's correlation identified 2 miRNAs (miR-367 and miR-30a-5p) associated with the NCI40 cell line in vitro paclitaxel response (P<0.0003). Ovarian cancer cells were selected based on the association between paclitaxel sensitivity and miR-367/miR-30a-5p expression. Overexpression of miR-367 in the paclitaxel-sensitive cells [PA1; IC50, 1.69 nM, high miR-367 (2.997), low miR-30a-5p (-0.323)] further increased paclitaxel sensitivity, whereas miR-367 depletion decreased paclitaxel sensitivity. In contrast, overexpression and depletion of miR-30a-5p in the paclitaxel-resistant cells [OVCAR4; IC50, 17.8 nM, low miR-367 (-0.640), high miR-30a-5p (3.270)] decreased and increased paclitaxel sensitivity, respectively. We identified and successfully targeted miRNAs associated with human cancer cell line response to paclitaxel. Our strategy of integrating in vitro miRNA expression and drug sensitivity data may not only aid in the characterization of determinants of drug response but also in the identification of novel therapeutic targets to increase activity of existing therapeutics.
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Copy and paste a formatted citation
Spandidos Publications style
Chen N, Chon HS, Xiong Y, Marchion DC, Judson PL, Hakam A, Gonzalez-Bosquet J, Permuth-Wey J, Wenham RM, Apte SM, Apte SM, et al: Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel. Oncol Rep 31: 376-383, 2014.
APA
Chen, N., Chon, H.S., Xiong, Y., Marchion, D.C., Judson, P.L., Hakam, A. ... Lancaster, J.M. (2014). Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel. Oncology Reports, 31, 376-383. https://doi.org/10.3892/or.2013.2847
MLA
Chen, N., Chon, H. S., Xiong, Y., Marchion, D. C., Judson, P. L., Hakam, A., Gonzalez-Bosquet, J., Permuth-Wey, J., Wenham, R. M., Apte, S. M., Cheng, J. Q., Sellers, T. A., Lancaster, J. M."Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel". Oncology Reports 31.1 (2014): 376-383.
Chicago
Chen, N., Chon, H. S., Xiong, Y., Marchion, D. C., Judson, P. L., Hakam, A., Gonzalez-Bosquet, J., Permuth-Wey, J., Wenham, R. M., Apte, S. M., Cheng, J. Q., Sellers, T. A., Lancaster, J. M."Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel". Oncology Reports 31, no. 1 (2014): 376-383. https://doi.org/10.3892/or.2013.2847
Copy and paste a formatted citation
x
Spandidos Publications style
Chen N, Chon HS, Xiong Y, Marchion DC, Judson PL, Hakam A, Gonzalez-Bosquet J, Permuth-Wey J, Wenham RM, Apte SM, Apte SM, et al: Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel. Oncol Rep 31: 376-383, 2014.
APA
Chen, N., Chon, H.S., Xiong, Y., Marchion, D.C., Judson, P.L., Hakam, A. ... Lancaster, J.M. (2014). Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel. Oncology Reports, 31, 376-383. https://doi.org/10.3892/or.2013.2847
MLA
Chen, N., Chon, H. S., Xiong, Y., Marchion, D. C., Judson, P. L., Hakam, A., Gonzalez-Bosquet, J., Permuth-Wey, J., Wenham, R. M., Apte, S. M., Cheng, J. Q., Sellers, T. A., Lancaster, J. M."Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel". Oncology Reports 31.1 (2014): 376-383.
Chicago
Chen, N., Chon, H. S., Xiong, Y., Marchion, D. C., Judson, P. L., Hakam, A., Gonzalez-Bosquet, J., Permuth-Wey, J., Wenham, R. M., Apte, S. M., Cheng, J. Q., Sellers, T. A., Lancaster, J. M."Human cancer cell line microRNAs associated with in vitro sensitivity to paclitaxel". Oncology Reports 31, no. 1 (2014): 376-383. https://doi.org/10.3892/or.2013.2847
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