BACKGROUND Gastric cancer (GC) is one of the most prevalent and deadly malignancies worldwide. Accumulating reports have indicated the participation of long non-coding RNAs (lncRNAs) in the onset and progression of GC. METHODS GSE109476 data was utilized to screen out lncRNAs dysregulated in GC. Gene expressions were determined by qRT-PCR and western blot. Both in vitro and in vivo experiments were carried out to assess the function of HOXC-AS1 in GC. The association between genes was verified via RIP, ChIP, CoIP, RNA pull down and luciferase reporter assays, as appropriate. RESULTS HOXC-AS1 was discovered to be upregulated in GC and located both in cytoplasm and in nucleus in GC cells. Functionally, inhibition of HOXC-AS1 restrained GC cell growth and metastasis both in vitro and in vivo. Moreover, HOXC-AS1 was proved to be trans-activated by c-MYC in GC. In return, HOXC-AS1 positively regulated MYC expression in GC through targeting miR-590-3p/MYC axis in cytoplasm and modulating BRG1/β-catenin complex-activated MYC transcription in nucleus. Furthermore, the rescue assays verified that MYC mediated HOXC-AS1-affected GC progression. CONCLUSION Our research illustrated a feedback loop of HOXC-AS1-MYC in aggravating GC cell growth and metastasis, highlighting HOXC-AS1 as a promising target for GC diagnosis and treatment.

中文翻译：

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HOXC-AS1-MYC调节环有助于胃癌的生长和转移。

背景技术胃癌（GC）是世界上最普遍和致命的恶性肿瘤之一。越来越多的报告表明，长的非编码RNA（lncRNA）参与了GC的发生和发展。方法利用GSE109476数据筛选出GC中失调的lncRNA。通过qRT-PCR和蛋白质印迹确定基因表达。进行了体外和体内实验，以评估HOXC-AS1在GC中的功能。基因之间的关联通过RIP，ChIP，CoIP，RNA下拉和荧光素酶报告基因检测进行了验证。结果发现HOXC-AS1在GC中被上调，并位于GC细胞的细胞质和细胞核中。从功能上讲，HOXC-AS1的抑制作用可在体外和体内抑制GC细胞的生长和转移。而且，证明HOXC-AS1在GC中被c-MYC反式激活。作为回报，HOXC-AS1通过靶向细胞质中的miR-590-3p / MYC轴并调节细胞核中的BRG1 /β-catenin复合物激活的MYC转录来积极调节GC中的MYC表达。此外，救援分析证实MYC介导的HOXC-AS1影响了GC进程。结论我们的研究阐明了HOXC-AS1-MYC在加重GC细胞生长和转移中的反馈回路，强调了HOXC-AS1作为GC诊断和治疗的有希望的靶标。