Research Paper Volume 12, Issue 9 pp 8605—8621
Identification and functional activity of matrix-remodeling associated 5 (MXRA5) in benign hyperplastic prostate
- 1 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
- 2 Department of Urology, People’s Hospital of Qichun County, Huanggang, China
- 3 Department of Surgery and Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
- 4 Current address: Urological Surgery, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
Received: September 24, 2019 Accepted: April 13, 2020 Published: May 11, 2020
https://doi.org/10.18632/aging.103175How to Cite
Copyright © 2020 Xiao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Benign prostatic hyperplasia (BPH) is a common condition in aging males. The current study aims to identify differentially expressed genes (DEGs) associated with BPH and to elucidate the role of matrix-remodeling associated 5 (MXRA5) protein and mitogen-activated protein kinase (MAPK) signaling pathways in BPH.
Results: A total of 198 DEGs and a number of related pathways were identified with MXRA5 being one of the most significantly altered DEGs. MXRA5 was upregulated in BPH samples and localized mostly in stroma. Knockdown of MXRA5 induced stromal cell cycle arrest instead of inhibiting apoptosis. Consistently, MXRA5 overexpression enhanced epithelial cell proliferation. In addition, phosphorylated ERK1/2 and p38, key members of the MAPK family, were strongly decreased with knockdown but increased with overexpression.
Conclusion: Our novel data demonstrates that upregulation of MXRA5 in the enlarged prostate could contribute to the development of BPH through increasing cell proliferation via the MAPK pathway. Thus, the MXRA5-MAPK system could be rediscovered as a new therapeutic target for treating BPH.
Methods: Microarray analysis and integrated bioinformatics were conducted. The expression and biologic functions of MXRA5 was investigated via RT-PCR, western-blot, immunofluorescence, flow cytometry and MTT assay. Finally, genes involved in regulation of the MAPK pathway were investigated.
Abbreviations
MXRA5: Matrix-remodeling associated 5; MAPK: Mitogen-activated protein kinase; BPH: Benign prostatic hyperplasia; DEGs: Differentially expressed genes; RT-PCR: Reverse transcription-polymerase chain reaction; MTT: 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide; ERK1/2: Extracellular signal-regulated kinase 1/2; LUTS: Lower urinary tract symptoms; WT1: Wilms tumor gene; EMT: Epithelial-mesenchymal transition; ECM: Extracellular matrix; NSCLC: Non-small cell lung cancer; CRC: Colorectal cancer; RMA: Robust Multichip Analysis.