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Circular RNA circRAB31 acts as a miR-885-5psponge to suppress gastric cancer progressionvia the PTEN/PI3K/AKT pathway.

ABSTRACT: Emerging evidence indicated that circular RNAs (circRNAs) play essential roles in cancer progression. A large number of circRNAs have been reported to modulate cancer carcinogenesis. However, the underlying mechanisms by which circRNAs regulate gastric cancer remain largely unclear. By using circRNA microarray, we identified that circRAB31 may serve as a tumor suppressor. circRAB31 was downregulated in gastric cancer tissues and gastric cancer cell lines compared with normal tissues and a human gastric epithelial cell line (GES-1). Overexpression of circRAB31 suppressed gastric cancer proliferation and metastasis in vitro and in vivo, whereas silencing of circRAB31 had the opposite effects. Bioinformatic analysis as well as pull-down and luciferase assays revealed that circRAB31 exerted tumor-suppressive functions by binding directly to miR-885-5p. In addition, we demonstrated that circRAB31 could suppress PI3K/AKT signaling via the phosphatase and tensin homologue (PTEN)-a downstream target gene of miR-885-5p. In summary, our results demonstrated that circRAB31 could serve as a sponge of miR-885-5p to regulate gastric cancer cell proliferation, migration, and invasion by affecting the PTEN/PI3K/AKT signaling.

SUBMITTER: Liang X

PROVIDER: S-EPMC8633833 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Periodontal ligament stem cells (PDLSCs) are the ideal seed cells for periodontal tissue regeneration. It is well established that persistent inflammation significantly impairs the osteogenic differentiation capability of PDLSCs. Therefore, maintaining PDLSC osteogenic potential under the inflammatory microenvironment is important for treating bone loss in periodontitis. The aim of our study was to explore the potential role of circular RNA BIRC6 (circBIRC6) in regulating osteogenic differentiation of PDLSCs in the inflammatory conditions. Methods Alkaline phosphatase staining, Alizarin Red staining, quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining were used to evaluated the effects of circBIRC6 on the osteogenic differentiation of PDLSCs. RNA pull-down and luciferase assays were performed to explore the interaction between circBIRC6 and miR-543. Then, the downstream signaling pathway affected by circBIRC6/miR-543 axis was further investigated. Results The expression level of circBIRC6 was higher in PDLSCs exposed to inflammatory stimulus and in periodontitis tissues compared to the respective controls. Downregulation of circBIRC6 enhanced the osteogenic potential of PDLSCs under the inflammatory conditions, and upregulation of circBIRC6 led to opposite findings. Mechanistically, we found that circBIRC6 modulated PDLSC osteogenic differentiation through sponging miR-543. More importantly, we have demonstrated that circBIRC6/miR-543 axis regulated the mineralization capacity of PDLSCs via PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment. Conclusions In summary, the expression of miR-543 is significantly increased following circBIRC6 downregulation, leading to inhibition of PTEN and subsequently activation of PI3K/AKT/mTOR signaling pathway. Therefore, targeting circBIRC6 might represent a potential therapeutic strategy for improving bone loss in periodontitis. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03093-7.

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Circular RNA circRAB31 acts as a miR-885-5psponge to suppress gastric cancer progressionvia the PTEN/PI3K/AKT pathway.

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