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HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer.

ABSTRACT: 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/?-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.

SUBMITTER: Dong Y

PROVIDER: S-EPMC6929373 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer.

Dong Yangyang Y Li Xinyu X Lin Zhibin Z Zou Wenbing W Liu Yan Y Qian Huiyang H Jia Jing J

Journal of experimental & clinical cancer research : CR 20191223 1

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 31870402

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Project description:Background: DC-STAMP domain containing 1-antisense 1 (DCST1-AS1) is a long noncoding RNA (lncRNA) that is up-regulated in triple-negative breast cancer (TNBC) tissues. Here, we attempt to investigate the oncogenic property of DCST1-AS1. Methods: LncRNA microarrays were used to detect differentially expressed lncRNA in cancerous tissues. Fluorescence in situ hybridization assay was used to detect the distribution of DCST1-AS1 in BT-549 and MDA-MB-231 cells. Lentiviral systems, inhibitors, siRNA and overexpression plasmids were used for gain- and loss-of-function experiments. Colony formation assay, wound healing assay, CCK8 assay, transwell assay, and flow cytometry assay were used to study the function of DCST1-AS1. Luciferase assay was used to verify the binding of MYC to the promoter region and the binding of miR-873-5p to DCST1-AS1. RNA immunoprecipitation assay was used to verify that argonaute 2 binds to both miR-873-5p and DCST1-AS1. Western blotting was used to measure changes in protein expression. Results: Consistent with the microarray results, we found that DCST1-AS1 was up-regulated in both TNBC tissue samples and cell lines. DCST1-AS1 was positively correlated with distant metastasis and histopathological grades. DCST1-AS1 is distributed in both nucleus and cytoplasm. Knockdown of DCST1-AS1 inhibits TNBC cell proliferation and metastasis, while overexpression of DCST1-AS1 promotes TNBC cell proliferation and metastasis. We confirmed that DCST1-AS1 expression in TNBC cells is regulated by MYC. Furthermore, we found that DCST1-AS1 is negatively correlated with miR-873-5p in TNBC tissues and is a direct target gene of miR-873-5p. Argonaute 2 is involved in the binding of DCST1-AS1 and miR-873-5p and promotes the degradation of DCST1-AS1. The interaction of DCST1-AS1 with miR-873-5p ultimately up-regulated the expression of insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), MYC, CD44 and lymphoid enhancer binding factor 1 (LEF1). Conclusions: DCST1-AS1 is activated by MYC and is degraded by binding to miR-873-5p, thereby upregulating the expression of miR-873-5p downstream proteins IGF2BP1, MYC, LEF1 and CD44. MYC, DCST1-AS1 and miR-873-5p form a positive regulatory loop to promote TNBC cell proliferation and metastasis.

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Dataset Information

HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer.

Publications

HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer.

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