Research Paper Volume 12, Issue 8 pp 7282—7298

HMGN5 promotes IL-6-induced epithelial-mesenchymal transition of bladder cancer by interacting with Hsp27

Kun Yao 1, 2, , Leye He 1, 2, , Yu Gan 1, 2, , Jianye Liu 1, 2, , Jin Tang 1, 2, , Zhi Long 1, 2, , Jing Tan 1, 2, ,

  • 1 Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan, P.R. China
  • 2 Institute of Prostate Disease, Central South University, Changsha 410013, Hunan, P.R. China

received: September 3, 2019 ; accepted: March 24, 2020 ; published: April 21, 2020 ;

https://doi.org/10.18632/aging.103076
How to Cite

Copyright © 2020 Yao 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

Bladder cancer (BC) is one of the most common cancers worldwide, with a high rate of recurrence and poor outcomes. High-mobility group nucleosome-binding domain 5 (HMGN5) is overexpressed in many cancers and could cause carcinogenesis in BC. By protein-protein-interaction (PPI) analysis, we found that heat shock protein 27 (Hsp27), also a crucial functional factor in BC carcinogenesis, is significantly related to HMGN5. Hsp27 is required for IL-6-mediated EMT via STAT3/Twist signaling in prostate cancer. Here, we hypothesize that HMGN5 may interact with Hsp27 to affect IL-6-induced EMT and invasion in BC via STAT3 signaling. In the present study, we found that HMGN5 and Hsp27 are highly expressed in BC tissues and positively correlated with each other. HMGN5 interacts with Hsp27 in vitro, to modulate the cell invasion and EMT in BC. Moreover, HMGN5 could modulate IL-6-Hsp27-induced EMT and invasion in BC cells by regulating STAT3 phosphorylation and STAT3 targeting of the Twist promoter. HMGN5 interacts with Hsp27 to promote tumor growth in a human BC xenograft model in nude mice. In summary, HMGN5 interacts with Hsp27 to promote IL-6-induced EMT, therefore promoting invasion in BC and contributing to the progression of BC.

Abbreviations

HMGN5: High-mobility group nucleosome-binding domain 5; PPI: Protein-Protein-Interaction; Hsp27: heat shock protein 27; TCC: transitional cell carcinoma; Hsps: Heat shock proteins; HE: Hematoxylin and eosin; IHC: Immunohistochemistry; IF: Immunofluorescence.