Dysregulation of miR-106a and miR-591 confers paclitaxel resistance to ovarian cancer
| Autor: | Ho Jung An, Dong Hyeon Lee, Song Ja, Kyu-Pyo Kim, Jeong Jy, Tae Hyo Kim, Minjong Lee, Young Kwan Kim, Huh Jh, Jung Yj |
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| Rok vydání: | 2013 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty endocrine system Paclitaxel medicine.disease_cause Downregulation and upregulation miR-591 Ovarian carcinoma Internal medicine Cell Line Tumor microRNA medicine Cluster Analysis Humans Molecular Diagnostics Ovarian Neoplasms business.industry Cell growth Transfection medicine.disease Microarray Analysis Antineoplastic Agents Phytogenic Survival Analysis Cystadenocarcinoma Serous paclitaxel resistance microRNAs Gene Expression Regulation Neoplastic ovarian cancer Drug Resistance Neoplasm miR-106a Cancer cell Cancer research Female Carcinogenesis business Ovarian cancer Transcriptome |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 |
| Popis: | Background: MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed. Methods: MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT–PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays. Results: Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay. Conclusion: MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1. |
| Databáze: | OpenAIRE |
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