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

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

doi:10.3892/or.2013.2847

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
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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
Published online on: November 13, 2013 https://doi.org/10.3892/or.2013.2847
Pages: 376-383

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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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1	Wani MC, Taylor HL, Wall ME, Coggon P and McPhail AT: Plant antitumor agents. VI The isolation and structure of Taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc. 93:2325–2327. 1971. View Article : Google Scholar : PubMed/NCBI
2	Schiff PB and Horwitz SB: Taxol assembles tubulin in the absence of exogenous guanosine 5′-triphosphate or microtubule-associated proteins. Biochemistry. 20:3247–3252. 1981.PubMed/NCBI
3	Schiff PB and Horwitz SB: Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA. 77:1561–1565. 1980. View Article : Google Scholar : PubMed/NCBI
4	Lim LP, Lau NC, Garrett-Engele P, et al: Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 433:769–773. 2005. View Article : Google Scholar : PubMed/NCBI
5	Cummins JM and Velculescu VE: Implications of micro-RNA profiling for cancer diagnosis. Oncogene. 25:6220–6227. 2006. View Article : Google Scholar : PubMed/NCBI
6	He H, Jazdzewski K, Li W, et al: The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 102:19075–19080. 2005. View Article : Google Scholar : PubMed/NCBI
7	Lu J, Getz G, Miska EA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
8	Chen CZ: MicroRNAs as oncogenes and tumor suppressors. N Engl J Med. 353:1768–1771. 2005. View Article : Google Scholar : PubMed/NCBI
9	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 94:776–780. 2006. View Article : Google Scholar : PubMed/NCBI
10	Johnson SM, Grosshans H, Shingara J, et al: RAS is regulated by the let-7 microRNA family. Cell. 120:635–647. 2005. View Article : Google Scholar : PubMed/NCBI
11	Corney DC, Flesken-Nikitin A, Godwin AK, Wang W and Nikitin AY: MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 67:8433–8438. 2007. View Article : Google Scholar : PubMed/NCBI
12	Chang TC, Wentzel EA, Kent OA, et al: Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 26:745–752. 2007. View Article : Google Scholar : PubMed/NCBI
13	Debernardi S, Skoulakis S, Molloy G, Chaplin T, Dixon-McIver A and Young BD: MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis. Leukemia. 21:912–916. 2007.PubMed/NCBI
14	Blower PE, Chung JH, Verducci JS, et al: MicroRNAs modulate the chemosensitivity of tumor cells. Mol Cancer Ther. 7:1–9. 2008. View Article : Google Scholar : PubMed/NCBI
15	Zheng T, Wang J, Chen X and Liu L: Role of microRNA in anticancer drug resistance. Int J Cancer. 126:2–10. 2010. View Article : Google Scholar : PubMed/NCBI
16	Boren T, Xiong Y, Hakam A, et al: MicroRNAs and their target messenger RNAs associated with ovarian cancer response to chemotherapy. Gynecol Oncol. 113:249–255. 2009. View Article : Google Scholar : PubMed/NCBI
17	Zheng A, Kallio A and Harkonen P: Tamoxifen-induced rapid death of MCF-7 breast cancer cells is mediated via extracellularly signal-regulated kinase signaling and can be abrogated by estrogen. Endocrinology. 148:2764–2777. 2007. View Article : Google Scholar
18	Ritchie ME, Silver J, Oshlack A, et al: A comparison of background correction methods for two-colour microarrays. Bioinformatics. 23:2700–2707. 2007. View Article : Google Scholar : PubMed/NCBI
19	Smyth GK and Speed T: Normalization of cDNA microarray data. Methods. 31:265–273. 2003. View Article : Google Scholar : PubMed/NCBI
20	Tusher VG, Tibshirani R and Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA. 98:5116–5121. 2001. View Article : Google Scholar : PubMed/NCBI
21	Bar M, Wyman SK, Fritz BR, et al: MicroRNA discovery and profiling in human embryonic stem cells by deep sequencing of small RNA libraries. Stem Cells. 26:2496–2505. 2008. View Article : Google Scholar : PubMed/NCBI
22	Wang X and El Naqa IM: Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics. 24:325–332. 2008. View Article : Google Scholar : PubMed/NCBI
23	Sontheimer EJ and Carthew RW: Silence from within: endogenous siRNAs and miRNAs. Cell. 122:9–12. 2005. View Article : Google Scholar : PubMed/NCBI
24	O’Donnell KA, Wentzel EA, Zeller KI, Dang CV and Mendell JT: c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 435:839–843. 2005.PubMed/NCBI
25	Blower PE, Verducci JS, Lin S, et al: MicroRNA expression profiles for the NCI-60 cancer cell panel. Mol Cancer Ther. 6:1483–1491. 2007. View Article : Google Scholar : PubMed/NCBI
26	Cittelly DM, Dimitrova I, Howe EN, et al: Restoration of miR-200c to ovarian cancer reduces tumor burden and increases sensitivity to paclitaxel. Mol Cancer Ther. 11:2556–2565. 2012. View Article : Google Scholar : PubMed/NCBI
27	Chen Y, Zuo J, Liu Y, Gao H and Liu W: Inhibitory effects of miRNA-200c on chemotherapy-resistance and cell proliferation of gastric cancer SGC7901/DDP cells. Chin J Cancer. 29:1006–1011. 2010. View Article : Google Scholar : PubMed/NCBI
28	Fujita Y, Kojima K, Ohhashi R, et al: MiR-148a attenuates paclitaxel resistance of hormone-refractory, drug-resistant prostate cancer PC3 cells by regulating MSK1 expression. J Biol Chem. 285:19076–19084. 2010. View Article : Google Scholar
29	Du L, Subauste MC, DeSevo C, et al: miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers. PLoS One. 7:e391672012.PubMed/NCBI
30	Catuogno S, Cerchia L, Romano G, Pognonec P, Condorelli G and de Franciscis V: miR-34c may protect lung cancer cells from paclitaxel-induced apoptosis. Oncogene. 32:341–351. 2013. View Article : Google Scholar : PubMed/NCBI
31	Holleman A, Chung I, Olsen RR, et al: miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo. Oncogene. 30:4386–4398. 2011. View Article : Google Scholar : PubMed/NCBI
32	Li J, Zhang Y, Zhao J, Kong F and Chen Y: Overexpression of miR-22 reverses paclitaxel-induced chemoresistance through activation of PTEN signaling in p53-mutated colon cancer cells. Mol Cell Biochem. 357:31–38. 2011. View Article : Google Scholar : PubMed/NCBI
33	Zhou M, Liu Z, Zhao Y, et al: MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J Biol Chem. 285:21496–21507. 2010. View Article : Google Scholar : PubMed/NCBI
34	Mei M, Ren Y, Zhou X, et al: Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat. 9:77–86. 2010. View Article : Google Scholar : PubMed/NCBI
35	Huang YW, Liu JC, Deatherage DE, et al: Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer. Cancer Res. 69:9038–9046. 2009. View Article : Google Scholar : PubMed/NCBI
36	Mialon A, Sankinen M, Soderstrom H, et al: DNA topoisomerase I is a cofactor for c-Jun in the regulation of epidermal growth factor receptor expression and cancer cell proliferation. Mol Cell Biol. 25:5040–5051. 2005. View Article : Google Scholar : PubMed/NCBI
37	Barroso-delJesus A, Romero-Lopez C, Lucena-Aguilar G, et al: Embryonic stem cell-specific miR302–367 cluster: human gene structure and functional characterization of its core promoter. Mol Cell Biol. 28:6609–6619. 2008.PubMed/NCBI
38	Lavon I, Zrihan D, Granit A, et al: Gliomas display a microRNA expression profile reminiscent of neural precursor cells. Neuro Oncol. 12:422–433. 2010.PubMed/NCBI
39	Sokilde R, Kaczkowski B, Podolska A, et al: Global microRNA analysis of the NCI-60 cancer cell panel. Mol Cancer Ther. 10:375–384. 2011. View Article : Google Scholar : PubMed/NCBI
40	Greither T, Grochola LF, Udelnow A, Lautenschlager C, Wurl P and Taubert H: Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 126:73–80. 2010. View Article : Google Scholar : PubMed/NCBI
41	Levati L, Alvino E, Pagani E, et al: Altered expression of selected microRNAs in melanoma: antiproliferative and proapoptotic activity of miRNA-155. Int J Oncol. 35:393–400. 2009.PubMed/NCBI
42	Pan X, Zhao J, Zhang WN, et al: Induction of SOX4 by DNA damage is critical for p53 stabilization and function. Proc Natl Acad Sci USA. 106:3788–3793. 2009. View Article : Google Scholar : PubMed/NCBI
43	Baraniskin A, Birkenkamp-Demtroder K, Maghnouj A, et al: MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL. Carcinogenesis. 33:732–739. 2012. View Article : Google Scholar : PubMed/NCBI
44	Yanaihara N, Caplen N, Bowman E, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
45	Marchini S, Cavalieri D, Fruscio R, et al: Association between miR-200c and the survival of patients with stage I epithelial ovarian cancer: a retrospective study of two independent tumour tissue collections. Lancet Oncol. 12:273–285. 2011. View Article : Google Scholar : PubMed/NCBI
46	Li X, Zhang Y, Zhang Y, Ding J, Wu K and Fan D: Survival prediction of gastric cancer by a seven-microRNA signature. Gut. 59:579–585. 2010. View Article : Google Scholar : PubMed/NCBI