PMID- 35075122 OWN - NLM STAT- MEDLINE DCOM- 20220408 LR - 20221024 IS - 2041-4889 (Electronic) VI - 13 IP - 1 DP - 2022 Jan 24 TI - Glucose-regulated protein 78 modulates cell growth, epithelial-mesenchymal transition, and oxidative stress in the hyperplastic prostate. PG - 78 LID - 10.1038/s41419-022-04522-4 [doi] LID - 78 AB - Benign prostatic hyperplasia (BPH) is a chronic condition which mainly affects elderly males. Existing scientific evidences have not completely revealed the pathogenesis of BPH. Glucose-regulated protein 78 (GRP78) is a member of the heat shock protein 70 superfamily, which serves as an important regulator in many diseases. This study aims at elucidating the role of GRP78 in the BPH process. Human prostate tissues, cultured human prostate cell lines (BPH-1 and WPMY-1) and clinical data from BPH patients were utilized. The expression and localization of GRP78 were determined with quantitative real time PCR (qRT-PCR), Western blotting and immunofluorescence staining. GRP78 knockdown and overexpression cell models were created with GRP78 siRNA and GRP78 plasmid transfection. With these models, cell viability, apoptosis rate, as well as marker levels for epithelial-mesenchymal transition (EMT) and oxidative stress (OS) were detected by CCK8 assay, flow cytometry analysis and Western blotting respectively. AKT/mTOR and MAPK/ERK pathways were also evaluated. Results showed GRP78 was localized in the epithelium and stroma of the prostate, with higher expression in BPH tissues. There was no significant difference in GRP78 expression between BPH-1 and WPMY-1 cell lines. In addition, GRP78 knockdown (KD) slowed cell growth and induced apoptosis, without effects on the cell cycle stage of both cell lines. Lack of GRP78 affected expression levels of markers for EMT and OS. Consistently, overexpression of GRP78 completely reversed all effects of knocking down GRP78. We further found that GRP78 modulated cell growth and OS via AKT/mTOR signaling, rather than the MAPK/ERK pathway. Overall, our novel data demonstrates that GRP78 plays a significant role in the development of BPH and suggests that GRP78 might be rediscovered as a new target for treatment of BPH. CI - (c) 2022. The Author(s). FAU - Fu, Xun AU - Fu X AUID- ORCID: 0000-0001-9180-364X AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Liu, Jianmin AU - Liu J AUID- ORCID: 0000-0001-7009-3116 AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Liu, Daoquan AU - Liu D AUID- ORCID: 0000-0002-2628-0229 AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Zhou, Yongying AU - Zhou Y AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Guo, Yuhang AU - Guo Y AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Wang, Zhen AU - Wang Z AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Yang, Shu AU - Yang S AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - He, Weixiang AU - He W AUID- ORCID: 0000-0002-4366-8321 AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Chen, Ping AU - Chen P AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Wang, Xinghuan AU - Wang X AUID- ORCID: 0000-0003-3497-0024 AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - DiSanto, Michael E AU - DiSanto ME AD - Department of Surgery and Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA. FAU - Zhang, Xinhua AU - Zhang X AUID- ORCID: 0000-0003-0267-428X AD - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. zhangxinhuad@163.com. LA - eng GR - 82070780/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 81770757/National Natural Science Foundation of China (National Science Foundation of China)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220124 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (HSPA5 protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Aged MH - Cell Cycle/genetics MH - *Endoplasmic Reticulum Chaperone BiP/genetics/metabolism MH - Epithelial-Mesenchymal Transition/genetics MH - Glucose/metabolism MH - Humans MH - Male MH - *Oxidative Stress MH - *Prostate/metabolism MH - *Prostatic Hyperplasia/metabolism MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - TOR Serine-Threonine Kinases/genetics/metabolism PMC - PMC8786955 COIS- The authors declare no competing interest. EDAT- 2022/01/26 06:00 MHDA- 2022/04/09 06:00 PMCR- 2022/01/24 CRDT- 2022/01/25 05:48 PHST- 2021/07/15 00:00 [received] PHST- 2022/01/11 00:00 [accepted] PHST- 2021/12/14 00:00 [revised] PHST- 2022/01/25 05:48 [entrez] PHST- 2022/01/26 06:00 [pubmed] PHST- 2022/04/09 06:00 [medline] PHST- 2022/01/24 00:00 [pmc-release] AID - 10.1038/s41419-022-04522-4 [pii] AID - 4522 [pii] AID - 10.1038/s41419-022-04522-4 [doi] PST - epublish SO - Cell Death Dis. 2022 Jan 24;13(1):78. doi: 10.1038/s41419-022-04522-4.