HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer.
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.
['Dong|Yangyang|Y|', 'Li|Xinyu|X|', 'Lin|Zhibin|Z|', 'Zou|Wenbing|W|', 'Liu|Yan|Y|', 'Qian|Huiyang|H|', 'Jia|Jing|J|']
D000818:Animals D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D004195:Disease Models, Animal D058750:Epithelial-Mesenchymal Transition D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D053263:Gene Regulatory Networks D016259:Genes, myc D064593:Heterografts D018398:Homeodomain Proteins D006801:Humans D051379:Mice D035683:MicroRNAs D008954:Models, Biological D009362:Neoplasm Metastasis D009367:Neoplasm Staging D062085:RNA, Long Noncoding D013274:Stomach Neoplasms
Gastric cancer HOXC-AS1 MYC miR-590-3p BRG1