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

ZOPPINO F. C. M.; GUERRERO M.; CAYADO-GUTIÉRREZ N.; CASTRO G. N.; CUELLO CARRION D.; FANELLI M. A.; CIOCCA D. R.

Huangshan

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 (luminal A cells) as a biological breast cancer model. The cells were transfected (miRNAmax, Invitrogen) either with hsa-miR-214 or with 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 HSPBl, either by western blot and/or confocal inmunofluorescence. Also we performed a RNA-Seq bioinformatic analysis of The Cancer Genome Atlas Project [TCGA], specifically we used breast cancer database. We examined 1,039 samples obtained at the time of initial diagnosis. Kaplan Meier curves for HSPB1 (categorical data) and hsa-rniR-214 (categorical data) were generated to analyze overall survival (OS). Results: We report that HSPB1 and phosphorylated HSPB1 are downregulated in MCF-7 cells transfected with hsa-miR-214. Moreover, beta-Catenin and PTEN, important proteins involved in cancer with demonstrated capacity to interact withHSPB1, presented an up-regulated express ion including phosphorylated forms ofPTEN in the transfected cells (hsa-miR-214). Our studies indicate that hsa-miR-214 increases the levels of the protumoral proteins Akt and phosphorylated Akt. We have found in luminal A breast cancer patients that high levels of HSPB1 were associated with significant increased survival. In contrast, patients with increased levels of hsa-rniR-214 presented significant poor survival; these observations were noted mainly in luminal A breast cancer patients. Conclusion: We report for the first time the participation of hsa-miR-214 in breast cancer biology and theirclínical significance.