Wang Huafeng, Zhang Benyan, Wang Xue, Mao Jianhua, Li Weiguang, Sun Yunwei, Yuan Yaozong, Ben Qiwen, Hua Li, Qian Aihua
Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Onco Targets Ther. 2020 Aug 21;13:8383-8394. doi: 10.2147/OTT.S256918. eCollection 2020.
Transient receptor potential vanilloid 4 (TRPV4) has been reported to be involved in the progression of several human tumors. Nevertheless, clinical significance and molecular mechanism of TRPV4 in gastric cancer (GC) remain poorly defined.
Immunohistochemistry assays were used to investigate the correlation between the expression of TRPV4 and epithelial-mesenchymal transition (EMT) markers in human GC tissues. The correlations between TRPV4 expression and clinicopathological features and between TRPV4 expression and survival rates were also examined. TRPV4 knockdown was performed by using small interfering RNAs. In vitro, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and transwell assay were employed to further explore the biological functions of TRPV4, and Western blotting was used to evaluate the changes in the expression of TRPV4 protein and EMT-related proteins in HGC-27 and MGC-803 human GC cell lines.
TRPV4 expression was upregulated in GC tissues and cell lines. TRPV4 overexpression was associated with greater depth of tumor invasion, lymph node metastasis, higher TNM stage, poor overall survival, and worse disease-free survival. TRPV4 expression was inversely correlated with E-cadherin expression and positively correlated with vimentin expression. In vitro, knockdown of TRPV4 inhibited GC cell proliferation, colony formation, and invasion. Furthermore, the knockdown of TRPV4 modulated EMT by upregulating E-cadherin expression and downregulating the expression of N-cadherin and vimentin. In addition, the EMT-related transcription factor Snail was downregulated, whereas the expression levels of other transcription factors such as Slug and Twist did not change.
TRPV4 was upregulated in human GC and the overexpression of TRPV4 could promote GC progression, partially through Snail-mediated EMT.
据报道，瞬时受体电位香草酸受体4（TRPV4）参与多种人类肿瘤的进展。然而，TRPV4在胃癌（GC）中的临床意义和分子机制仍不清楚。
采用免疫组织化学分析研究人GC组织中TRPV4表达与上皮-间质转化（EMT）标志物之间的相关性。还检测了TRPV4表达与临床病理特征之间以及TRPV4表达与生存率之间的相关性。通过使用小干扰RNA进行TRPV4基因敲低。在体外，采用细胞计数试剂盒-8（CCK-8）检测、集落形成检测和Transwell检测进一步探索TRPV4的生物学功能，并使用蛋白质印迹法评估人GC细胞系HGC-27和MGC-803中TRPV4蛋白和EMT相关蛋白表达的变化。
GC组织和细胞系中TRPV4表达上调。TRPV4过表达与肿瘤浸润深度增加、淋巴结转移、更高的TNM分期、较差的总生存期和无病生存期相关。TRPV4表达与E-钙黏蛋白表达呈负相关，与波形蛋白表达呈正相关。在体外，敲低TRPV4可抑制GC细胞增殖、集落形成和侵袭。此外，敲低TRPV4通过上调E-钙黏蛋白表达和下调N-钙黏蛋白及波形蛋白表达来调节EMT。此外，EMT相关转录因子Snail下调，而其他转录因子如Slug和Twist的表达水平未改变。
人GC中TRPV4上调，TRPV4过表达可促进GC进展，部分通过Snail介导的EMT实现。
