Regulation of HSPB1 (HSP27) by hsa-miR- 214 in breast cancer

ZOPPINO FELIPE CARLOS MARTIN; GUERRERO GIMENEZ, MARTIN EDUARDO; CASTRO, GISELA NATALIA; CAYADO-GUTIÉRREZ NIUBYS

Huangshan, China

Congreso; VIIth International Congress on Stress Response in Biology and Medicine; 2015

Cell Stress Society International

Aim: To evaluate effects of hsa-miR-214 on HSPB1 in the context of breast cancer. Methods: We used MCF-7, classified as luminal A cells, as biological model of breast cancer. The cells were transfected (miRNAmax, Invitrogen) either with hsa-miR-214 or a negative control miRNA. After 48 hours we evaluated the expression of HSPB1 and its phosphorylated variant at residue Ser78 by western blot. We studied known proteins that interact with HSPB1, either by western blot and/or confocal inmunofluorescence. Also we realized RNA-Seq bioinformatic analysis of The Cancer Genome Atlas Project [TCGA], specifically we used breast cancer database. We examined 1039 samples obtained at the time of initial diagnosis. Kaplan Meier curves for HSPB1 (categorical data) and hsa-miR-214 (categorical data) were generated to analyze overall survival (OS). Results: In this study, we report that HSPB1 and phosphorylated HSPB1 are downregulated in MCF-7 cells transfected with hsa-miR-214. Moreover, βCatenin and PTEN, important proteins involved in cancer with demonstrated capacity to interact with HSPB1, present an up-regulated expression including phosphorylated forms of PTEN. Ours studies indicate that has-miR-214 increase the levels of the protumoral proteins Akt and phosphorylated Akt. We have found in luminal A breast cancer that high levels of HSPB1 provoke decreased of survival. Also, patients with increased levels of hsa-miR-214 have an impaired survival. This is more important in luminal A breast cancer. Conclusion: We account for first time the participation of hsa-miR-214 in breast cáncer. This study could address HSPB1 as molecular player involved in hsa-miR-214 action.