American Association for Cancer Research
00085472can121400-sup-t4_xls_164kb.xls (295 kB)

Supplementary Table 4 from Cisplatin Sensitivity Mediated by WEE1 and CHK1 Is Mediated by miR-155 and the miR-15 Family

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posted on 2023-03-30, 21:30 authored by Lynn M. Pouliot, Yu-Chi Chen, Jennifer Bai, Rajarshi Guha, Scott E. Martin, Michael M. Gottesman, Matthew D. Hall

XLs file - 164K, Results from kinome siRNA screen



Resistance to platinum-based therapies arises by multiple mechanisms, including by alterations to cell-cycle kinases that mediate G2–M phase arrest. In this study, we conducted parallel high-throughput screens for microRNAs (miRNA) that could restore sensitivity to cisplatin-resistant cells, and we screened for kinases targeted by miRNAs that mediated cisplatin resistance. Overexpression of the cell-cycle kinases WEE1 and CHK1 occurred commonly in cisplatin-resistant cells. miRNAs in the miR-15/16/195/424/497 family were found to sensitize cisplatin-resistant cells to apoptosis by targeting WEE1 and CHK1. Loss-of-function and gain-of-function studies showed that miR-15 family members controlled the expression of WEE1 and CHK1. Supporting these results, we found that in the presence of cisplatin altering expression of miR-16 or related genes altered cell cycle distribution. Our findings reveal critical regulation of miRNAs and their cell-cycle–associated kinase targets in mediating resistance to cisplatin. Cancer Res; 72(22); 5945–55. ©2012 AACR.