PURPOSE Based on previous researches of HoxC6, this study aims to investigate the expression levels of isoforms HoxC6-1 and HoxC6-2 and to explore their roles in gastric carcinogenesis as well as the possible molecular mechanism. METHODS We investigated expression levels of HoxC6, HoxC6-1, and HoxC6-2 in gastric cancer tissues, coupled with relevant data in TCGA dataset. In vitro, HoxC6, HoxC6-1, and HoxC6-2 knockdown by small interference RNA was carried for evaluating the changes of malignant biological behaviors of gastric cancer cells, such as proliferation, migration, invasion, apoptosis, and cell cycle alternation. Metastasis-related nucleotide lncRNA HOTAIR was selected by bioinformatics, and verification was carried out by in vitro researches. RESULTS Data suggested HoxC6-1 and HoxC6-2 were considerably over-expressed with different folds in gastric cancerous tissues. Decreased expression of HoxC6-2 was detected in well-differentiated type of gastric cancer. In vitro, the conclusion that HoxC6 functions as a tumor oncogene illuminated by previous studies was verified again. Additionally, down-regulating of HoxC6-2 significantly inhibited SGC-7901 and BGC-823 cells from proliferation, migration, invasion, apoptosis, while quite slight results or none statistically significant results were observed when HoxC6-1 was knockdown. Besides, over-expression of HOTAIR, which is relevant with HoxC6 during gastric carcinogenesis, was detected in gastric cancerous tissues. Restored expression of HoxC6 partially reversed the decreased migration caused by down-regulating HOTAIR in gastric cancer cells. CONCLUSION HoxC6 acts as an oncogene in gastric carcinogenesis and might be a promising therapeutic target. Isoform HoxC6-2 plays a primary carcinogenic role in gastric carcinogenesis. HOTAIR, over-expressed in gastric cancer, might regulate HoxC6 on the protein level in promoting migration of gastric cells.

中文翻译：

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HoxC6作为癌基因和同工型HoxC6-2可能在胃癌发生中起主要作用。

目的基于HoxC6的先前研究，本研究旨在研究HoxC6-1和HoxC6-2同工型的表达水平，并探讨其在胃癌发生中的作用以及可能的分子机制。方法我们结合TCGA数据集中的相关数据，研究了HoxC6，HoxC6-1和HoxC6-2在胃癌组织中的表达水平。在体外，通过小干扰RNA敲低HoxC6，HoxC6-1和HoxC6-2来评估胃癌细胞的恶性生物学行为的变化，例如增殖，迁移，侵袭，凋亡和细胞周期改变。通过生物信息学选择与转移相关的核苷酸lncRNA HOTAIR，并通过体外研究进行验证。结果数据表明，HoxC6-1和HoxC6-2在胃癌组织中明显过量表达，并具有不同的倍数。在高分化型胃癌中检测到HoxC6-2表达降低。在体外，HoxC6作为先前研究阐明的肿瘤癌基因的结论再次得到证实。此外，HoxC6-2的下调显着抑制了SGC-7901和BGC-823细胞的增殖，迁移，侵袭，凋亡，而当敲除HoxC6-1时，观察到的结果很小或没有统计学意义。此外，在胃癌组织中检测到与HoxC6相关的HOTAIR过表达。HoxC6的恢复表达部分逆转了由于下调胃癌细胞中HOTAIR引起的迁移减少。结论HoxC6在胃癌发生中起癌基因的作用，可能是有希望的治疗靶标。亚型HoxC6-2在胃癌发生中起主要致癌作用。在胃癌中过度表达的HOTAIR可能在促进胃细胞迁移的蛋白质水平上调节HoxC6。