American Association for Cancer Research
00085472can120103-sup-can_12-0103_f11_t2_1094k.pdf (1.07 MB)

Supplementary Figures 1-11, Tables 1-2 from MiR-96 Downregulates REV1 and RAD51 to Promote Cellular Sensitivity to Cisplatin and PARP Inhibition

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journal contribution
posted on 2023-03-30, 21:06 authored by Yemin Wang, Jen-Wei Huang, Philamer Calses, Christopher J. Kemp, Toshiyasu Taniguchi

PDF file - 1MB, Figure S1. Overexpression of miR-183-96-182 cluster miRNAs in U2OS cells. Figure S2. Effects of miR-183-96-182 cluster miRNAs on cisplatin-induced foci formation of RAD51, RPA2, FANCD2 and BRCA1. Figure S3. Overexpression of miR-96 sensitizes cancer cells to cisplatin and AZD2281. Figure S4. Overexpression of miR-96 sensitizes HR-deficient cancer cells to cisplatin. Figure S5. MiR-96 is highly conserved across species. Figure S6. Conservation of miR-96 binding sites and surrounding regions in the transcripts of REV1 and RAD51. Figure S7. Combinational treatment with miR-96 and cisplatin delayed tumor growth. Figure S8. Effects of miR-183-96-182 cluster miRNA mimics on cellular sensitivity to cisplatin and AZD2281. Figure S9. Effects of IR on the expression of miR-183-96-182 cluster miRNAs. Figure S10. Effect of miR-183-96-182 cluster miRNAs on BRCA1 and REV1 expression. Figure S11. Effect of miR-183-96-182 cluster miRNAs on cell growth. Supplementary Tables S1-S2 Table S1. Top 100 predicted targets of miR-96 by each miRNA prediction algorithm. Table S2. Predicted miR-96 targets by at least two prediction algorithms



Cell survival after DNA damage relies on DNA repair, the abrogation of which causes genomic instability. The DNA repair protein RAD51 and the trans-lesion synthesis DNA polymerase REV1 are required for resistance to DNA interstrand cross-linking agents such as cisplatin. In this study, we show that overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage. MiR-96 directly targeted the coding region of RAD51 and the 3′-untranslated region of REV1. Overexpression of miR-96 decreased the efficiency of homologous recombination and enhanced sensitivity to the PARP inhibitor AZD2281 in vitro and to cisplatin both in vitro and in vivo. Taken together, our findings indicate that miR-96 regulates DNA repair and chemosensitivity by repressing RAD51 and REV1. As a therapeutic candidate, miR-96 may improve chemotherapeutic efficacy by increasing the sensitivity of cancer cells to DNA damage. Cancer Res; 72(16); 4037–46. ©2012 AACR.

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