Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 14, Issue 2, Pages 3802-3816Publisher
MDPI
DOI: 10.3390/ijms14023802
Keywords
miR-17 similar to 92 cluster; transduction; ovarian carcinoma; paclitaxel resistance; PTEN; BIM
Funding
- Natural Science Foundation of China [30973189]
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To better understand the molecular mechanisms of paclitaxel resistance in ovarian carcinoma, we evaluated the expression of miRNAs using miRNA microarray between human ovarian carcinoma SKOV3 cells and paclitaxel resistant SKOV3-TR30 cells. Results showed that 69 miRNAs were upregulated while 102 miRNAs were downregulated in SKOV3-TR30 cells. Using real-time PCR, we further clarified that miR-17 similar to 92 was overexpressed in SKOV3-TR30 cells compared with that in SKOV3 cells. We then established stable virally transduced SKOV3-TR30-m-PTIP-Sponge all SKOV3-TR30 cells and its vector-only control SKOV3-TR30-m-PTIP-GFP cells. Real time-PCR revealed that SKOV3-TR30-m-PTIP-Sponge all cells expressed approximately 6.18-fold lower levels of miR-17 similar to 92 compared with the control group. Decreased expression of miR-17 similar to 92 resulted in cell cycle arrest in the G2/M phase and growth inhibition. After the transduction, the BIM protein level was increased in SKOV3-TR30 cells and luciferase reporter assays revealed that miR-17 similar to 92 binds directly to the 3'-UTR of BIM. Results of luciferase reporter assays accompanied with Western Blot showed that although miR-17 similar to 92 binds directly to the 3'-UTR of PTEN, the PTEN protein expression level was upregulated slightly while the result is of no statistical significance. Our results showed that miR-17 similar to 92 could be a causal factor of the downregulation of BIM in SKOV3-TR30 cells and thus induce the paclitaxel resistance in SKOV3-TR30 cells.
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