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Circ_100984-miR-432-3p axis regulated c-Jun/YBX-1/β-catenin feedback loop promotes bladder cancer progression.

ABSTRACT: Bladder cancer (BC) is one of the most commonly diagnosed cancers globally. Recently, circular RNAs (circRNAs) have been revealed to participate in BC progression with diverse mechanisms. However, mechanisms of circ_100984 in BC have not been determined. Here, we found that circ_100984 and YBX-1 were high presented, while miR-432-3p was low presented in BC. Silencing of circ_100984 and YBX-1 repressed BC tumor growth, migration, and invasion in vitro and in vivo. Mechanistically, we revealed that circ_100984 served as a competing endogenous RNA that sponged miR-432-3p to indirectly regulate YBX-1 and epithelial-mesenchymal transition (EMT)-related molecules. Moreover, we confirmed that YBX-1 or c-Jun acted as a transcription regulatory factor for β-catenin or YBX-1, respectively, in BC cells. Knockdown of YBX-1 inhibited the expression of β-catenin and c-Jun, whereas downregulated c-Jun inversely repressed the expression of YBX-1 and β-catenin. Our results suggested that circ_100984-miR-432-3p axis regulated c-Jun/YBX-1/β-catenin feedback loop promotes BC progression, providing a potential therapeutic axis for BC progression.

SUBMITTER: Tong L

PROVIDER: S-EPMC8019231 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAs novel biomarkers for various cancers, microRNAs negatively regulate genes expression via promoting mRNA degradation and suppressing mRNA translation. miR-589 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in gastric cancer. Here, we aim to investigate the biological effect of miR-589 on gastric cancer and to reveal the possible mechanism.MethodsReal-time PCR was performed to evaluate the expression of miR-589 in 34 paired normal and stomach tumor specimens, as well as gastric cell lines. Functional assays, such as wound healing, transwell assays and in vivo assays, were used to detect the biological effect of miR-589 and LIFR. We determined the role of miR-589 in gastric cancer tumorigenesis in vivo using xenograft nude models. Dual-luciferase report assays and Chromatin immunoprecipitation (ChIP) assay were performed for target evaluation, and the relationships were confirmed by western blot assay.ResultMiR-589 expression was significantly higher in tumor tissues and gastric cancer cells than those in matched normal tissues and gastric epithelial cells, respectively. Clinically, overexpression of miR-589 is associated with tumor metastasis, invasion and poor prognosis of GC patients. Gain- and loss-of function experiments showed that miR-589 promoted cell migration, metastasis and invasion in vitro and lung metastasis in vivo. Mechanistically, we found that miR-589 directly targeted LIFR to activate PI3K/AKT/c-Jun signaling. Meanwhile, c-Jun bound to the promoter region of miR-589 and activated its transcription. Thus miR-589 regulated its expression in a feedback loop that promoted cell migration, metastasis and invasion.ConclusionOur study identified miR-589, as an oncogene, markedly induced cell metastasis and invasion via an atypical miR-589-LIFR-PI3K/AKT-c-Jun feedback loop, which suggested miR-589 as a potential biomarker and/or therapeutic target for the gastric cancer management.

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Circ_100984-miR-432-3p axis regulated c-Jun/YBX-1/β-catenin feedback loop promotes bladder cancer progression.

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