Abstract
BackgroundGastric 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.MethodsGSE109476 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.ResultsHOXC-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.ConclusionOur 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.
Highlights
Gastric cancer (GC) is the most prevalent and deadly cancer type in gastrointestinal system around the world [1, 2]
Overexpressed HOXC-AS1 in GC locates both in the cytoplasm and nucleus of GC cells To recognize the long non-coding RNAs (lncRNAs) implicated in the development of GC, we analyzed the expression profile of dysregulated mRNAs and lncRNAs in GC tissues and adjacent normal tissues from GEO dataset numbered GSE109476
It was indicated that only HOXCAS1 was obviously upregulated in GC tissues relative to the para-carcinoma tissues, whereas no significant enhancement of HOXC-AS3 expression was observed in GC tissues in contrast to adjacent non-cancerous tissues (Fig. 1d)
Summary
Gastric cancer (GC) is the most prevalent and deadly cancer type in gastrointestinal system around the world [1, 2]. Surgical resection is undisputedly the only strategy to cure GC patients, while most of the cases have developed into advanced stages and are unsuitable for surgery [3, 4]. In order to develop effective therapeutic strategies to prolong the lifespan of GC patients, our priority is to understand the pathogenesis and detailed mechanisms underlying GC development. Data from GSE109476 revealed that HOXCAS1 was apparently highly-expressed in GC tissues compared to the normal tissues 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
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