C-MYC and BCL-2 mediate YAP-regulated tumorigenesis in OSCC.
C-MYC and BCL-2 mediate YAP-regulated tumorigenesis in OSCC.
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C-MYC 和 BCL-2 介导 YAP 调节的 OSCC 肿瘤发生
DOI：
10.18632/oncotarget.23089
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发表时间：
2018-01-02
期刊：
影响因子：
--
通讯作者：
Wen Y
中科院分区：
文献类型：
--
作者：
Chen X;Gu W;Wang Q;Fu X;Wang Y;Xu X;Wen Y
转录共激活因子是相关蛋白(YAP)，是哺乳动物细胞中的关键癌基因。目前对YAP在口腔鳞状细胞癌(OSCC)中的表达仍不清楚。本研究旨在探讨YAP对口腔鳞癌细胞增殖和凋亡的影响及其分子机制。结果表明，YAP在口腔鳞癌组织中的表达水平高于癌旁正常组织。在CAL27细胞系中，YAP基因的敲除抑制了细胞的增殖，促进了细胞的凋亡。反之，过表达YAP可保护细胞免于凋亡，促进细胞增殖。此外，由于YAP的差异表达，C-MYC和bcl2的mRNA和蛋白水平也发生了变化。随后在CAL27细胞中用维替普芬处理后发现，bcl2和c-myc的转录和翻译都降低了。在异种移植瘤模型中，YAP基因的敲除抑制了CAL27的体内肿瘤生长，而YAP过表达则促进了肿瘤的生长。这些结果表明，YAP是一个重要的调节因子，通过影响细胞周期和内在的凋亡信号在口腔鳞状细胞癌中发挥促增殖和抗凋亡的作用。因此，YAP有可能成为口腔鳞癌治疗中有价值的分子生物学标志物或治疗靶点。
Transcriptional co-activator Yes-associated protein (YAP) is a key oncogene in mammalian cells. The present understanding of YAP in oral squamous cells carcinoma (OSCC) remains unclear. The purpose of this study is to investigate the effects of YAP on proliferation and apoptosis in OSCC and the molecular mechanism. The results showed the expression level of YAP was higher in OSCC tissues than that in adjacent normal tissues. Knockdown of YAP in CAL27 cell lines prohibited cell proliferation while augmented apoptosis. Conversely, overexpression of YAP protected cells from apoptosis and promoted cell proliferation. Moreover, C-MYC and BCL-2 mRNA and protein levels were altered due to the differential expression of YAP. Subsequent Verteporfin treatment in CAL27 cells revealed that the transcription and translation of BCL-2 and C-MYC both decreased. In a tumor xenograft model, knockdown of YAP suppressed tumor growth of CAL27 in vivo, while YAP overexpression promoted the tumor growth. These results suggest that YAP is a crucial regulator that exerts pro-proliferation and anti-apoptosis effects in OSCC through actions affecting the cell cycle and intrinsic apoptotic signaling. Thus YAP could potentially serve as a valuable molecular biomarker or therapeutic target in the treatment of OSCC.
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