miR-375 is upregulated in acquired paclitaxel resistance in cervical cancer.

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.

• Authors: Y Shen, P Wang, Y Li, F Ye, F Wang, X Wan, X Cheng, W Lu, X Xie
• Journal: British journal of cancer (Br J Cancer) Vol. 109 Issue 1 Pg. 92-9 (Jul 09 2013) ISSN: 1532-1827 [Electronic] England
• PMID: 23778521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• MIRN375 microRNA, human
• MicroRNAs
• Paclitaxel

Topics

• Adult
• Aged
• Animals
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Cell Line, Tumor
• Drug Resistance, Neoplasm (genetics)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (biosynthesis, genetics)
• Middle Aged
• Paclitaxel (therapeutic use)
• Up-Regulation
• Uterine Cervical Neoplasms (drug therapy, genetics, metabolism)
• Young Adult