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STRA6 exerts oncogenic role in gastric tumorigenesis by acting as a crucial target of miR-873.

ABSTRACT: BACKGROUND:Increasing evidence shows that stimulated by retinoic acid 6 (STRA6) participates in regulating multiple cancers. However, the biological roles of STRA6 in gastric cancer (GC) remain unknown. This study aimed to investigate the biological function of STRA6 and reveal the underlying mechanism of its dysregulation in GC. METHODS:The expression level of STRA6 was detected through quantitative real-time PCR and Western blot analysis. The effects of STRA6 on the proliferation of GC cells were studied through CCK-8 proliferation, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays. The effects of STRA6 on migration and invasion were detected via wound healing and Transwell assays. Upstream miRNAs, which might regulate STRA6 expression, was predicted through bioinformatics analysis. Their interaction was further confirmed through dual-luciferase reporter assays and rescue experiments. RESULTS:STRA6 was up-regulated in GC and enhanced the proliferation and metastasis of GC cells in vitro and in vivo. STRA6 knockdown could inhibit the Wnt/?-catenin signalling pathway. STRA6 was confirmed as an miR-873 target, which acted as a tumour suppressor in GC. Rescue assays showed that the repressing effect of miR-873 could be partially reversed by overexpressing STRA6. CONCLUSIONS:STRA6 is down-regulated by miR-873 and plays an oncogenic role by activating Wnt/?-catenin signalling in GC.

SUBMITTER: Lin L

PROVIDER: S-EPMC6836487 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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STRA6 exerts oncogenic role in gastric tumorigenesis by acting as a crucial target of miR-873.

Lin Linling L Xiao Jian J Shi Liang L Chen Wangwang W Ge Yugang Y Jiang Mingkun M Li Zengliang Z Fan Hao H Yang Li L Xu Zekuan Z

Journal of experimental & clinical cancer research : CR 20191106 1

<h4>Background</h4>Increasing evidence shows that stimulated by retinoic acid 6 (STRA6) participates in regulating multiple cancers. However, the biological roles of STRA6 in gastric cancer (GC) remain unknown. This study aimed to investigate the biological function of STRA6 and reveal the underlying mechanism of its dysregulation in GC.<h4>Methods</h4>The expression level of STRA6 was detected through quantitative real-time PCR and Western blot analysis. The effects of STRA6 on the proliferatio ...[more]

PMID: 31694721

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Project description:Background: Hypoxia is a crucial factor in the progression of various tumors, including gastric cancer (GC). Circular RNAs (circRNAs) are important regulators in GC, and this study focused on researching circC6orf132 in GC progression under hypoxia. Methods: In vitro experiments were performed in GC cells under hypoxia (1% O2). CircC6orf132, microRNA-873-5p (miR-873-5p), and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) levels were examined by real-time polymerase chain reaction (qRT-PCR). Colony formation assay and transwell assay were used for detecting cell proliferation and migration or invasion. Glycolytic metabolism was evaluated using lactate production, glucose uptake, and adenosine triphosphate (ATP) level and extracellular acidification rate (ECAR). Western blotting was performed for determining protein expression. The target interaction was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo assay was conducted via mouse xenograft model. Results: The expression of circC6orf132 was significantly high in GC cells under hypoxia. Hypoxia-induced GC proliferation, migration, invasion, and glycolysis were reversed by silencing circC6orf132. CircC6orf132 targeted miR-873-5p; and the inhibition of circC6orf132 knockdown for the effects of hypoxia on GC cells was abrogated by miR-873-5p inhibitor. PRKAA1 was validated as a downstream gene of miR-873-5p, and miR-873-5p functioned as an anticancer molecule in GC cells under hypoxia by downregulating PRKAA1 level. CircC6orf132 could regulate PRKAA1 by sponging miR-873-5p. CircC6orf132/miR-873-5p/PRKAA1 axis could regulate GC progression under the hypoxic condition. CircC6orf132 downregulation reduced tumorigenesis in vivo through affecting the miR-873-5p/PRKAA1 axis. Conclusion: CircC6orf132 has been affirmed to promote proliferation, migration, invasion, and glycolysis in GC under hypoxia, partly by depending on the regulation of miR-873-5p/PRKAA1 axis.

Dataset Information

STRA6 exerts oncogenic role in gastric tumorigenesis by acting as a crucial target of miR-873.

Publications

STRA6 exerts oncogenic role in gastric tumorigenesis by acting as a crucial target of miR-873.

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