HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer
HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer
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HOXA10在胃癌中诱导BCL2表达、抑制细胞凋亡并促进细胞增殖
DOI：
10.1002/cam4.2440
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发表时间：
2019-07-30
期刊：
影响因子：
4
通讯作者：
Zhou, Chongzhi
中科院分区：
文献类型：
--
作者：
Song, Chenlong;Han, Yang;Zhou, Chongzhi
Homeobox A10(HOXA10)在促进肿瘤发生中起关键作用，但HOXA10与胃癌表型之间的潜在机制仍不清楚。在本研究中，我们分析和验证了HOXA10和BCL2在胃癌组织中的表达在mRNA和蛋白水平上的升高。上调HOXA10基因在体外可促进胃癌细胞增殖，减少细胞凋亡率，促进体内肿瘤生长。生物信息学分析和实时定量聚合酶链式反应(qRT-PCR)实验推测HOXA10可能上调bcl2的表达。通过蛋白质印迹、染色质免疫沉淀和定量聚合酶链式反应(ChIP-qPCR)和挽救实验，我们发现HOXA10可能与bcl2启动子区域结合，诱导其表达，从而抑制内在的细胞凋亡途径。此外，HOXA10和BCL2的高表达预示着GC患者的总体生存率(OS)较差。综上所述，我们的研究表明HOXA10在胃癌中表达上调，并且HOXA10可能通过上调bcl2表达和抑制细胞凋亡来促进细胞增殖。
Homeobox A10 (HOXA10) has been implicated critical for the promotion of carcinogenesis, but the underlying mechanism between HOXA10 and malignant gastric cancer (GC) phenotype remains elusive. In the present study, we analyzed and validated that HOXA10 and BCL2 expressions were elevated both at the mRNA and protein levels in GC tissues. Upregulated HOXA10 promoted GC cell proliferation with reduced apoptosis in vitro and accelerated GC tumor growth in vivo. Bioinformatics analysis and quantitative real‐time polymerase chain reaction (qRT‐PCR) experiment inferred that HOXA10 might upregulate the expression of BCL2. By performing western blot, chromatin immunoprecipitation and quantitative PCR (ChIP‐qPCR), and rescue experiment, we found that HOXA10 might bind to BCL2 promoter region, induce its expression, and thus inhibit intrinsic apoptosis pathway. Moreover, higher expression of HOXA10 and BCL2 predicted poor overall survival (OS) in GC patients. In summary, our study indicated that HOXA10 was upregulated in GC, and that HOXA10 might promote cell proliferation by elevating BCL2 expression and inhibiting apoptosis.