miR-375 is upregulated in acquired paclitaxel resistance in cervical cancer |
| |
Authors: | Y Shen P Wang Y Li F Ye F Wang X Wan X Cheng W Lu X Xie |
| |
Institution: | 1.Women''s Reproductive Health Laboratory of Zhejiang Province, Women''s Hospital, School of Medicine, Zhejiang University, Hangzhou, China;2.Department of Gynecologic Oncology, Women''s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China |
| |
Abstract: | Background: Chemo-resistance is one of the key causal factors in cancer death and emerging evidences suggest that microRNAs (miRNAs) have critical roles in the regulation of chemo-sensitivity in cancers. Cervical cancer is one of the most common malignancies in women and insensitive to chemotherapy clinically.Methods: The differentially expressed miRNAs in cervical squamous cell carcinoma tissues were screened by using a microarray platform (μParaflo Sanger miRBase release 13.0). The expression of miR-375 was determined by stem-loop RT–PCR using 23 clinical cervical cancer samples and 2 cervical cancer cell lines. We exogenously upregulated miR-375 expression in SiHa and Caski cells using a pre-miRNA lentiviral vector transfection and observed its impact on paclitaxel sensitivity using MTS. The cells that stably overexpressed miR-375 were subcutaneously injected into mice to determine tumour growth and chemo-sensitivity in vivo.Results: Twenty-one differentially expressed miRNAs were found by miRNA microarray between pro- and post-paclitaxel cervical cancer tissues. Of those, miR-375 showed consistent high expression levels across paclitaxel-treated cervical cells and tissues. Paclitaxel induced upregulated miR-375 expression in a clear dose-dependent manner. Forced overexpression of miR-375 in cervical cancer cells decreased paclitaxel sensitivity in vitro and in vivo.Conclusion: Collectively, our results suggest that miR-375 might be a therapeutic target in paclitaxel-resistant cervical cancer. |
| |
Keywords: | miR-375 paclitaxel chemo-resistance cervical cancer |
|
|