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.
Highlights
Bladder cancer is one of the most common malignant tumors globally with a high rate of recurrence and poor outcomes, as a result of relapse
heat shock protein 27 (Hsp27) and High-mobility group nucleosome-binding domain 5 (HMGN5) mRNA expression was remarkably upregulated in 56 cases bladder cancer tissues (Figure 1C, 1D), and the expression levels were positively correlated with each other (Figure 1E)
Hsp27 overexpression further enhanced the promoting effect of HMGN5 overexpression (Figure 3A–3C), suggesting that HMGN5 interacts with Hsp27 to modulate bladder cancer cell invasion and epithelial-mesenchymal transition (EMT)
Summary
Bladder cancer is one of the most common malignant tumors globally with a high rate of recurrence and poor outcomes, as a result of relapse. Of all primary bladder cancers, approximately 90% are transitional cell carcinomas, 5% are squamous cell carcinomas, and 1– 2% are adenocarcinomas [1, 2]. Recent emerging research has reported that HMGN5 is overexpressed in many human cancers and that HMGN5 is related to carcinogenesis in a variety of cancer models [5], including bladder cancer [6]. To study how HMGN5 exerts its effects on bladder cancer cell invasion and epithelial-mesenchymal transition (EMT), a crucial issue during cancer metastasis, we performed protein-protein-interaction (PPI) analysis to search for factors related to HMGN5. Heat shock protein 27 (Hsp27), another crucial functional factor in bladder cancer carcinogenesis [8, 9], drew our attention
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