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HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer.
Cancer Medicine ( IF 2.9 ) Pub Date : 2019-07-30 , DOI: 10.1002/cam4.2440 Chenlong Song 1 , Yang Han 2, 3 , Huan Luo 4 , Zhiwei Qin 1 , Zhengqian Chen 1 , Yuan Liu 1 , Su Lu 5 , Huimin Sun 5 , Chongzhi Zhou 1
Cancer Medicine ( IF 2.9 ) Pub Date : 2019-07-30 , DOI: 10.1002/cam4.2440 Chenlong Song 1 , Yang Han 2, 3 , Huan Luo 4 , Zhiwei Qin 1 , Zhengqian Chen 1 , Yuan Liu 1 , Su Lu 5 , Huimin Sun 5 , Chongzhi Zhou 1
Affiliation
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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.
中文翻译：
HOXA10诱导BCL2表达，抑制细胞凋亡并促进胃癌中的细胞增殖。
同源盒A10（HOXA10）已被认为对促进致癌作用至关重要，但HOXA10与恶性胃癌（GC）表型之间的潜在机制仍然难以捉摸。在本研究中，我们分析并验证了HOXA10和BCL2的表达在GC组织的mRNA和蛋白水平上均升高。上调的HOXA10促进了GC细胞的增殖，减少了体外的细胞凋亡，并加速了GC的体内肿瘤生长。生物信息学分析和定量实时聚合酶链反应（qRT-PCR）实验表明，HOXA10可能上调BCL2的表达。通过进行蛋白质印迹，染色质免疫沉淀和定量PCR（ChIP-qPCR）和救援实验，我们发现HOXA10可能与BCL2启动子区域结合，诱导其表达，从而抑制内在的凋亡途径。此外，HOXA10和BCL2的较高表达预示了GC患者的总体生存期（OS）较差。总之，我们的研究表明HOXA10在GC中被上调，并且HOXA10可能通过提高BCL2表达和抑制细胞凋亡来促进细胞增殖。
更新日期：2019-07-31
中文翻译：
HOXA10诱导BCL2表达，抑制细胞凋亡并促进胃癌中的细胞增殖。
同源盒A10（HOXA10）已被认为对促进致癌作用至关重要，但HOXA10与恶性胃癌（GC）表型之间的潜在机制仍然难以捉摸。在本研究中，我们分析并验证了HOXA10和BCL2的表达在GC组织的mRNA和蛋白水平上均升高。上调的HOXA10促进了GC细胞的增殖，减少了体外的细胞凋亡，并加速了GC的体内肿瘤生长。生物信息学分析和定量实时聚合酶链反应（qRT-PCR）实验表明，HOXA10可能上调BCL2的表达。通过进行蛋白质印迹，染色质免疫沉淀和定量PCR（ChIP-qPCR）和救援实验，我们发现HOXA10可能与BCL2启动子区域结合，诱导其表达，从而抑制内在的凋亡途径。此外，HOXA10和BCL2的较高表达预示了GC患者的总体生存期（OS）较差。总之，我们的研究表明HOXA10在GC中被上调，并且HOXA10可能通过提高BCL2表达和抑制细胞凋亡来促进细胞增殖。
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