Dataset Information

LncRNA CASC2 inhibits lipopolysaccharide?induced acute lung injury via miR?27b/TAB2 axis.

ABSTRACT: Long non?coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) has been reported to exert an important role in acute lung injury (ALI). The present study aimed to investigate the potential underlying mechanism of CASC2 in ALI progression. Reverse transcription?quantitative PCR was conducted to examine the expression of CASC2, microRNA (miR/miRNA)?27b and TGF?? activated kinase 1 and MAP3K7?binding protein 2 (TAB2) in A549 cells. Cell viability and apoptosis were analyzed using 3?(4,5?dimethylthiazol?2?yl)?2,5?diphenyltetrazolium bromide assay and flow cytometry. Enzyme?linked immunosorbent assay was used to measure the levels of inflammatory?related cytokines to assess the inflammatory response, including interleukin?1? (IL?1?), IL?6 and tumor necrosis factor ? (TNF??). The binding sites of miR?27b in CASC2 or TAB2 were predicted using LncBase or microT?CDS software, following which dual?luciferase reporter and RNA binding protein immunoprecipitation assays were performed to confirm the target relationship between miR?27b and CASC2 or TAB2. The protein expression of TAB2 was detected by western blotting. The decreased viability, and increased apoptosis and inflammatory responses were attenuated by the accumulation of CASC2 in lipopolysaccharide (LPS)?stimulated A549 cells. CASC2 could directly bind to miR?27b in A549 cells. CASC2 protected A549 cells from LPS?triggered injury by downregulating miR?27b. TAB2 was a target of miR?27b in A549 cells. The influence of miR?27b depletion was reversed by the silencing of TAB2 in an ALI cell model. CASC2 could increase the expression of TAB2 by serving as a competing endogenous RNA of miR?27b in A549 cells. Collectively, the results suggested that CASC2 attenuated LPS?induced injury in the ALI cell model by modulating the miR?27b/TAB2 axis.

SUBMITTER: Li X

PROVIDER: S-EPMC7646969 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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lncRNA CASC2 inhibits lipopolysaccharide‑induced acute lung injury via miR‑27b/TAB2 axis.

Li Xiaoquan X Mo Jingxin J Li Jun J Chen Yalin Y

Molecular medicine reports 20201016 6

Long non‑coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) has been reported to exert an important role in acute lung injury (ALI). The present study aimed to investigate the potential underlying mechanism of CASC2 in ALI progression. Reverse transcription‑quantitative PCR was conducted to examine the expression of CASC2, microRNA (miR/miRNA)‑27b and TGF‑β activated kinase 1 and MAP3K7‑binding protein 2 (TAB2) in A549 cells. Cell viability and apoptosis were analyzed using 3‑(4,5‑dim ...[more]

PMID: 33174006

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Project description:Recently, it has been reported that long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a novel tumor suppressor, participates in regulating the carcinogenesis and suppresses tumor progression by sponging microRNAs (miRNAs). However, the expression and function of CASC2 in hepatocellular carcinoma (HCC) remain unclear.The expression of CASC2 and miR-367 in HCC specimens and cell lines were detected by real-time PCR. Western blotting and immunohistochemistry were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers in HCC. Transwell assays were used to determine migration and invasion of HCC cells. A mouse model for lung metastasis was established to evaluated HCC metastasis in vivo. The correlation among CASC2, miR-367 and F-box and WD repeat domain containing 7 (FBXW7) were disclosed by a dual-luciferase reporter assay, RIP assay and biotin pull-down assay.Here, CASC2 expression was significantly downregulated in HCC tissues, especially in aggressive and recurrent cases. In accordance, CASC2 underexpression was observed in HCC cell lines compared to LO2. In vitro and in vivo experiments revealed that CASC2 inhibited migration and invasion of HCC cells. Additionally, CASC2 repressed EMT process of HCC cells. Further studies demonstrated that CASC2 could function as a competing endogenous RNA (ceRNA) by sponging miR-367 in HCC cells. Functionally, gain- and loss-of-function studies showed that miR-367 promoted migration, invasion and EMT progression of HCC cells. Moreover, further investigations disclosed that FBXW7 was a downstream target of miR-367 and CASC2 prohibited EMT progression and subsequently exerted its anti-metastatic effects via CASC2/miR-367/FBXW7 axis in HCC cells. Clinically, CASC2 underexpression and miR-367 overexpression were closely correlated with the metastasis-associated clinicopathologic features. Notably, CASC2 low-expressing and miR-367 high-expressing HCC patients showed the poorest clinical outcome.Overall, we conclude that the CASC2/miR-367/FBXW7 axis may be a ponderable and promising therapeutic target for HCC.

Project description:BackgroundAcute lung injury (ALI) is a common clinical complication with a high mortality rate. Resveratrol (Res) has been shown to protect against ALI, but the role of long noncoding RNAs (lncRNAs) in this process is still unclear.MethodsMale rats (n=20) aged 7-8 weeks were randomly divided into four groups: control, lipopolysaccharide (LPS), LPS + Res, and LPS + dexamethasone (Dexa). Intragastric administration of Res (0.5 mg/kg) or Dexa (1.5 mg/kg) was performed 1 h before intraperitoneal injection of LPS (5 mg/kg). Lung tissue, serum, and bronchoalveolar lavage fluid were sampled 6 h after LPS treatment for inflammatory factor detection, pathological detection, lncRNA sequencing and bioinformatical analysis, and TdT-mediated dUTP Nick-End Labeling. Quantitative real time polymerase chain reaction and western blotting were used to verify the sequencing results. LPS, Res, and RNA interference were used in rat alveolar epithelial cells experiments to confirm the protective of Res/lncRNA against ALI.ResultsRes pretreatment inhibited lung injury and the increase of inflammatory cytokines induced by LPS. The differentially expressed lncRNAs and mRNAs (P<0.05 and |fold change| >2) were mainly involved in the signaling pathway of immunity, infection, signaling molecules and interactions. Among the lncRNAs and mRNAs, 26 mRNAs and 23 lncRNAs had high levels in lungs treated with LPS but decreased with Res, and 17 mRNAs and 27 lncRNAs were at lower levels in lungs treated with LPS but increased with Res. lncRNA and adjacent mRNA analysis showed that lncRNAs XLOC_014869 and the adjacent gene Fos, and the possible downstream genes Jun and Faslg were increased by LPS, but these changes were attenuated by Res. Pretreatment with Res reduced LPS-induced lung tissue apoptosis. Similarly, Res treatment and knockdown of lncRNA XLOC_014869 reduced LPS-induced apoptosis and the levels of Fos, c-Jun, and Fas-L.ConclusionsRes can inhibit the increase of lncRNAs XLOC_014869 caused by LPS stimulation and inhibit lung cell apoptosis. These effects may be due to lncRNA XLOC_014869 mediation of the pro-apoptotic factors (Fos, c-Jun, and Fas-L).

Dataset Information

LncRNA CASC2 inhibits lipopolysaccharide?induced acute lung injury via miR?27b/TAB2 axis.

Publications

lncRNA CASC2 inhibits lipopolysaccharide‑induced acute lung injury via miR‑27b/TAB2 axis.

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