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HOXA10 诱导 BCL2 表达,抑制细胞凋亡,促进胃癌细胞增殖。

HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer.

机构信息

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

出版信息

Cancer Med. 2019 Sep;8(12):5651-5661. doi: 10.1002/cam4.2440. Epub 2019 Jul 30.

Abstract

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.

摘要

Homeobox A10 (HOXA10) 被认为对促进癌症发生至关重要,但 HOXA10 与恶性胃癌 (GC) 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 的表达在 GC 组织中均在 mRNA 和蛋白水平上上调。上调的 HOXA10 促进 GC 细胞增殖,体外减少细胞凋亡,并加速体内 GC 肿瘤生长。生物信息学分析和实时定量聚合酶链反应 (qRT-PCR) 实验推断,HOXA10 可能上调 BCL2 的表达。通过进行 Western blot、染色质免疫沉淀和定量 PCR (ChIP-qPCR) 以及挽救实验,我们发现 HOXA10 可能结合到 BCL2 启动子区域,诱导其表达,从而抑制内在凋亡途径。此外,HOXA10 和 BCL2 的高表达预示着 GC 患者总体生存 (OS) 不良。总之,我们的研究表明 HOXA10 在 GC 中上调,HOXA10 可能通过提高 BCL2 表达和抑制细胞凋亡来促进细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a1b/6745829/6e9dfa334bba/CAM4-8-5651-g001.jpg

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