Chen Wenchao, Wu Gang, Zhu Yuanzeng, Zhang Wei, Zhang Han, Zhou Yang, Sun Peichun
Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People's Republic of China.
Cancer Manag Res. 2019 Jul 15;11:6625-6635. doi: 10.2147/CMAR.S201342. eCollection 2019.
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. 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. 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. This study demonstrates that HOXA10 functions as an oncogene in gastric cancer through activating JAK1/STAT3 signaling.
据报道，HOXA10在包括胃癌在内的多种癌症中表达失调。但其在胃癌进展中的作用存在争议。因此，本研究旨在探讨HOXA10在胃癌中的作用及机制。采用免疫组化（IHC）和蛋白质免疫印迹法（Western blotting）检测胃癌组织和细胞中HOXA10的表达。利用慢病毒感染改变胃癌NCI - N87和MKN28细胞中HOXA10、信号转导与转录激活因子3（STAT3）和Janus激酶1（JAK1）的表达。通过MTT法、克隆形成实验、流式细胞术和体内异种移植实验评估细胞增殖、克隆形成、凋亡和肿瘤发生情况。与正常胃组织样本和细胞相比，HOXA10在胃癌组织和细胞中的表达明显增加。HOXA10的上调显著增强了胃癌细胞的增殖、克隆形成和肿瘤发生能力，降低了细胞凋亡，并促进了JAK1/STAT3信号通路的激活。此外，我们发现当JAK1或STAT3表达下调时，HOXA10对细胞活力促进、肿瘤发生及细胞凋亡抑制的作用均减弱。本研究表明，HOXA10通过激活JAK1/STAT3信号通路在胃癌中发挥癌基因作用。
