Dataset Information

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

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.

SUBMITTER: Yao K

PROVIDER: S-EPMC7202510 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Yao Kun K He Leye L Gan Yu Y Liu Jianye J Tang Jin J Long Zhi Z Tan Jing J

Aging 20200421 8

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 prostat ...[more]

PMID: 32315283

Similar Datasets

Project description:BackgroundMetastatic bladder cancer (BLCA) is a lethal disease with an unmet need for study. Transgelin (TAGLN) is an actin-binding protein that affects the dynamics of the actin cytoskeleton indicating its robust potential as a metastasis initiator. Here, we sought to explore the expression pattern of TAGLN and elucidate its specific functioning and mechanisms in BLCA.MethodsA comprehensive assessment of TAGLN expression in BLCA was performed in three cohorts with a total of 847 patients. The potential effects of TAGLN on BLCA were further determined using clinical genomic analyses that guided the subsequent functional and mechanistic studies. In vitro migration, invasion assays and in vivo metastatic mouse model were performed to explore the biological functions of TAGLN in BLCA cells. Immunofluorescence, western blot and correlation analysis were used to investigate the molecular mechanisms of TAGLN.FindingsTAGLN was highly expressed in BLCA and correlated with advanced prognostic features. TAGLN promoted cell colony formation and cell migration and invasion both in vitro and in vivo by inducing invadopodia formation and epithelial-mesenchymal transition, during which a significant correlation between TAGLN and Slug was observed. The progression-dependent correlation between TGF-β and TAGLN was analysed at both the cellular and tissue levels, while TGF-β-mediated migration was abolished by the suppression of TAGLN.InterpretationOverall, TAGLN is a promising novel prognosis biomarker of BLCA, and its metastatic mechanisms indicate that TAGLN may represent a novel target agent that can be utilized for the clinical management of invasive and metastatic BLCA. FUND: This work was supported by the National Natural Science Foundation of China [81772703, 81672546, 81602253]; the Natural Science Foundation of Beijing [71772219, 7152146]. and Innovative Fund for Doctoral Students of Peking University Health Science Center (BUM2018BSS002). Funders had no role in the design of the study, data collection, data analysis, interpretation, or the writing of this report.

Project description:Bladder cancer (BLCA) is the 9th most common cancer of mortality. Autophagy and epithelial to mesenchymal transition (EMT) have an essential role in cancer invasion and metastasis. However, the relationship between autophagy and EMT is still poorly understood in BLCA. Functional enrichment and pathway network analysis were carried out. Comprehensive protein-protein interactions (PPI) networks were proposed to prioritize candidate autophagy-related genes. Furthermore, an autophagy-related signature and a nomogram model were established by integrating clinical information and this signature risk score to evaluate candidate autophagy-related genes. RAB14 expression and its association with pathological information and survival were evaluated in samples from TCGA dataset. Knocking down RAB14 in T24 cells was constructed, and immunofluorescence staining, transmission electron microscopy, immunohistochemistry and western blotting and a series of functional assays were performed to evaluate the migration, invasion, EMT and autophagy abilities of BLCA cells. The autophagy-related gene RAB14 was the only candidate gene identified by three kinds of analytic approaches. RAB14 was highly upregulated in BLCA and correlated with clinical outcomes based on TCGA BLCA datasets. Knocking down RAB14 was found to inhibit EMT and autophagy in T24 cells. RAB14 levels were positively related to those of LC3B and Beclin1, two genes with critical roles in the autophagy process, and the correlation was further confirmed in clinical tissue specimens by IHC and western blot analysis. In addition, RAB14-promoted EMT, migration, and invasion in T24 cells could be partially reversed by autophagy activator, rapamycin. The effects of RAB14 on autophagy was associated with level of p-Akt, indicating that they were possibly mediated via PI3K/AKT signaling. These findings indicated that autophagy-related gene RAB14-promoted EMT, migration and invasion of bladder cancer via the Akt-associated autophagic pathway.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets