MicroRNA profile of cisplatin resistant ovarian carcinoma

Mohammad Ghazizadeh, Hajime Shimizu, Ramin Ghazizadeh, Seiko Egawa


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.


Ovarian carcinoma cells, cisplatin resistance, microRNA profile

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