HOXA10 deteriorates gastric cancer through activating JAK1/STAT3 signaling pathway
HOXA10 deteriorates gastric cancer through activating JAK1/STAT3 signaling pathway
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DOI：
10.2147/cmar.s201342
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Sun, Peichun
中科院分区：
文献类型：
--
作者：
Chen, Wenchao;Wu, Gang;Sun, Peichun
背景：HOXA 10在包括胃癌在内的多种肿瘤中表达失调。但它在胃癌进展中的作用是有争议的。因此，本研究拟探讨HOXA 10在胃癌中的作用及其机制。材料与方法：采用免疫组化和Western blotting方法检测HOXA 10在胃癌组织和细胞中的表达。慢病毒感染改变胃癌NCI-N87和MKN 28细胞中HOXA 10、STAT3和JAK 1的表达。采用MTT法、克隆形成实验、流式细胞术和体内异种移植实验检测细胞增殖、克隆形成、凋亡和成瘤性。HOXA 10的上调可显著增强胃癌细胞的增殖、克隆形成和成瘤能力，减少胃癌细胞的凋亡，并促进JAK 1/STAT 3信号通路的激活。结论：HOXA 10作为一种癌基因，通过激活JAK1/STAT3信号通路在胃癌中发挥作用。
Background: HOXA10 has been reported to be deregulated in many kinds of cancers including gastric cancer. But its role in gastric cancer progression is controversial. Therefore, the current study was performed to explore the role and mechanism of HOXA10 in gastric cancer.Materials and methods: IHC and Western blotting assays were used to assess HOXA10 expression in gastric cancer tissues and cells. Lentivirus infection was used to alter HOXA10, STAT3 and JAK1 expression in gastric cancer NCI-N87 and MKN28 cells. MTT, cloning formation, flow cytometry and in vivo xenotransplantation experiments were carried out to assess cell proliferation, cloning formation, apoptosis and tumorigenesis.Results: HOXA10 expression was obviously increased in gastric cancer tissues and cells when compared with the normal gastric tissue samples and cells. Upregulation of HOXA10 significantly enhanced cell proliferation, cloning formation and tumorigenesis abilities and reduced cell apoptosis in gastric cancer, and promoted the activation of JAK1/STAT3 signaling. In addition, we showed that the effects of HOXA10 on the promotion of cell viability and tumorigenesis and cell apoptosis repression were all weakened when JAK1 or STAT3 was downregulated.Conclusion: This study demonstrates that HOXA10 functions as an oncogene in gastric cancer through activating JAK1/STAT3 signaling.