Neoplasma Vol.65, No.6, p.915-924, 2018
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| Title: SLC27A2 regulates miR-411 to affect chemo-resistance in ovarian cancer |
| Author: F. D. Chen, H. H. Chen, S. C. Ke, L. R. Zheng, X. Y. Zheng |
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Abstract: Although platinum-based chemotherapies have long been used as standard treatment in ovarian cancer, cisplatin resistance is a major problem that restricts its use. Herein, we investigate the biological function of SLC27A2 and its underlying mechanisms in regulating chemo-resistance in ovarian cancer. The findings show that SLC27A2 down-regulation in primary ovarian cancer tissues correlates with chemo-resistance and poor patient survival in our patient cohort. Significantly, we demonstrate that up-regulation of SLC27A2 by lentivirus-mediated p-SLC27A2 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo via apoptosis. Mechanistic investigation reveals that miR-411 is the most strikingly over-expressed gene in response to ectopic expression of SLC27A2, but under-expressed in recurrent ovarian cancer tissues. Lower miR-411 expression contributes to ovarian cancer chemo-resistance in vitro and in vivo. Furthermore, SLC27A2 directly binds specific sites in the miR-411 promoter region and promoter activity decreases after mutation of putative SLC27A2-binding sites. This indicates that SLC27A2 is required for the transcriptional induction of miR-411. The luciferase assays also confirm that miR-411 directly targets ABCG2 in ovarian cancer, and overall findings establish the SLC27A2-miR-411-ABCG2 pathway in the regulation of ovarian cancer chemo-resistance with potential therapeutic applications.
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| Keywords: ovarian cancer, SLC27A2, miR-411, ABCG2, chemo-resistance |
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Published online: 08-Oct-2018
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| Year: 2018, Volume: 65, Issue: 6 |
Page From: 915, Page To: 924 |
doi:10.4149/neo_2018_180122N48
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