MicroRNA profile of cisplatin resistant ovarian carcinoma

Mohammad Ghazizadeh, Hajime Shimizu, Ramin Ghazizadeh, Seiko Egawa

Abstract


Chemotherapy is a major part of cancer therapy with DNA-damaging drugs being effective in clinical practice. One such drug, cisplatin, has significant anti-tumor activity against a wide variety of solid tumors and is currently approved to treat metastatic ovarian cancer and testicular cancers. Resistance to cisplatin is a major impediment to successful treatment. On the other hand, microRNAs may have potential involvement in drug resistance. Here, we briefly review the concept of drug resistance particularly as related to the cisplatin and the microRNA profiles associated with development of cisplatin resistance in ovarian carcinoma based on the available literature including our own data. As for our experiments, a panel of cisplatin-resistant ovarian carcinoma cell lines A2780/CP, 2008/C13, and IGROV-1/CP and their corresponding parental cell lines were cultured in growth medium in the presence of 1mmol cisplatin as stimulant. Small RNAs were isolated using mirVana Kit and subjected to a high throughput microRNA profile analysis. Statistical and clustering analyses were performed using ANOVA and paired t-tests. Validation of the microRNA results was by real time qRT-PCR. Differential microRNA microarray profiles have demonstrated the involvement of a number of microRNAs in platinum-based drug resistant ovarian cancer cell lines. These included upregulation of miR-130a, miR-27a, miR-451, miR-214 and downregulation of let-7i in the drug-resistant cell lines. In addition, higher expression of miR-27a and miR-23a was observed in drug-resistant ovarian cancer tissues which were significantly correlated with prognosis. The results of our own experiments revealed upregulation of miR-23a and miR-23b in cisplatin resistant A2780/CP and 2008/C13 ovarian cancer cell line. Taken together, these studies demonstrate that overexpression of distinct microRNAs may provide new targets for the development of novel therapeutics to overcome cisplatin resistance in ovarian cancer and prompt further in-depth studies on miR-23 family and miR-27a in relation to cisplatin resistance.


Keywords


Ovarian carcinoma cells, cisplatin resistance, microRNA profile

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References


Ovarian cancer statistics, 2018. CA Cancer J Clin 2018. doi: 10.3322/caac.21456.

Boulikas T, and Vougiouka M. Cisplatin and platinum drugs at the molecular level. Oncol Rep 10: 1663- 1682, 2003.

Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular mechanisms of cisplatin resistance. Oncogene 31:1869-1883, 2012.

Sedletska Y, Giraud-Panis MJ, Malinge JM. Cisplatin is a DNA-damaging antitumour compound triggering multifactorial biochemical responses in cancer cells: importance of apoptotic pathways. Curr Med Chem Anticancer Agents 5:251-265, 2005.

Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed

RNAs. Science 294:853-858, 2001.

Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G, Ferlini C. Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol 111:478-486, 2008.

Zhu H, Wu H, Liu X, Evans BR, Medina DJ, Liu CG,

Yang JM. Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol 76:582-588, 2008.

Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV, Cheng JQ. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 68:425-433, 2008.

Yang N, Kaur S, Volinia S, Greshock J, Lassus H, Hasegawa K, Liang S, Leminen A, Deng S, Smith L, Johnstone CN, Chen XM, Liu CG, Huang Q, Katsaros D,

Calin GA, Weber BL, Bützow R, Croce CM, Coukos G,

Zhang L. MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res 68:10307-10314, 2008.

Eitan R, Kushnir M, Lithwick-Yanai G, David MB, Hoshen M, Glezerman M, Hod M, Sabah G, Rosenwald S, Levavi H. Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecol Oncol 114:253-259, 2009.

Zong C, Wang J, Shi TM. MicroRNA 130b enhances drug resistance in human ovarian cancer cells. Tumour Biol 35:12151-12156, 2014.

Jin AH, Zhou XP, Zhou FZ. Inhibition of microRNA-23a increases cisplatin sensitivity of ovarian cancer cells: the possible molecular mechanisms. Nan Fang Yi Ke Da Xue Xue Bao 35:125-128, 2015.

Dong H, Zitt C, Auriga C, Hatzelmann A, Epstein PM. Inhibition of PDE3, PDE4 and PDE7 potentiates glucocorticoid-induced apoptosis and overcomes glucocorticoid resistance in CEM T leukemic cells. Biochem Pharmacol 79:321-329, 2010.

Yamanaka Y, Mammoto T, Kirita T, Mukai M, Mashimo T, Sugimura M, Kishi Y and Nakamura H. Epinephrine inhibits invasion of oral squamous carcinoma cells by modulating intra-cellular cAMP. Cancer Lett 176:143-148, 2002.

McEwan DG, Brunton VG, Baillie GS, Leslie NR, Houslay MD, Frame MC. Chemoresistant KM12C colon cancer cells are addicted to low cyclic AMP levels in a phosphodiesterase 4-regulated compartment via effects on phosphoinositide 3-kinase. Cancer Res 67:5248-5257. 2007.

Kahn BB, Rossetti L, Lodish HF, Charron MJ. Decreased in vivo glucose uptake but normal expression of GLUT1 and GLUT4 in skeletal muscle of diabetic rats. J Clin Invest 87:2197-2206, 1999.

Marta De Donato, Mara Fanelli, Marisa Mariani, Giuseppina Raspaglio, Deep Pandya, Shiquan He, Paul Fiedler, Marco Petrillo, Giovanni Scambia, Cristiano Ferlini. Nek6 and Hif-1α cooperate with the cytoskeletal gateway of drug resistance to drive outcome in serous ovarian cance. Am J Cancer Res 5:1862-1877, 2015.


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