MicroRNA-296: a promising target in the pathogenesis of atherosclerosis?

Li, Heng; Ouyang, Xin; Jiang, Ting; Zheng, Xi-Long; He, Ping; Zhao, Guo-Jun

doi:10.1186/s10020-018-0012-y

Cited by 36 publications

(28 citation statements)

References 61 publications

(93 reference statements)

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“…It functions as a tumor suppressor in cervical, pancreatic and colorectal cancer by regulating specific targets (8)(9)(10). miR-296-3p is derived from the 3' arm of mature miR-296, and miR-296-5p is derived from the 5' arm (11). In NSCLC, miR-296-5p has been demonstrated to suppress tumor progression by targeting polo like kinase 1 (12).…”

Section: Introductionmentioning

confidence: 99%

miR‑296‑3p targets APEX1 to suppress cell migration and invasion of non‑small‑cell lung cancer

2019

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Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-associated mortality worldwide. MicroRNAs (miRs) are a class of small non-coding RNAs that are commonly dysregulated in human cancer. The aim of the current study was to evaluate the effect of miR-296-3p on the cell migration and invasion of NSCLC. Pairs of tumor tissues and para-cancerous tissues (n=50) were collected from patients with NSCLC, and the expression of miR-296-3p was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, tumor cell viability, migration and invasion were examined in vitro using Cell Counting Kit-8, wound healing and Matrigel assays, respectively. Furthermore, potential targets of miR-296-3p were screened for using TargetScan and validated using a dual-luciferase reporter assay. The expression levels of phosphoinositide-3-kinase (PI3K), AKT serine/threonine kinase (AKT), mammalian target of rapamycin (mTOR), matrix metallopeptidase 2 (MMP2) and SRY-box 4 (SOX4) were detected by RT-qPCR and western blot analysis. The data indicated that miR-296-3p was downregulated in tumor tissues compared with adjacent normal tissues. Overexpression of miR-296-3p inhibited NSCLC cell viability, migration and invasion in vitro. Furthermore, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) was identified as a direct target of miR-296-3p. APEX1 expression was upregulated in tumor tissues compared with para-cancerous tissues, and the mRNA and protein expression levels of APEX1 were decreased following transfection of NSCLC cells with miR-296-3p mimics compared with control cells. Additional investigations revealed that miR-296-3p was involved in regulating the PI3K/AKT/mTOR signaling pathway, and miR-296-3p mimics decreased the mRNA and protein expression levels of MMP2 and SOX4. In summary, the findings demonstrated that miR-296-3p may function as a tumor suppressor, and inhibits the migration and invasion of NSCLC cells by targeting APEX1. miR-296-3p is therefore a potential therapeutic molecular modulator of NSCLC.

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Section: Introductionmentioning

confidence: 99%

miR‑296‑3p targets APEX1 to suppress cell migration and invasion of non‑small‑cell lung cancer

2019

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“…It is also known that miR-296-5p regulates genes involved in inflammation, angiogenesis, hypertension, cholesterol metabolism, cellular proliferation, and apoptosis. Previous literature suggested it to be a promising target of atherosclerosis, an inflammatory disease in the vascular wall [27]. Given the disturbances in blood circulation and the inflammatory nature of I/R injury, it is reasonable to defer that miR-296-5p may be a key contributor to the pathogenesis of intestinal I/R injury.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline

et al. 2020

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Background: Hydrogen-rich saline (HRS) has been proven effective against ischemia/reperfusion (I/R) injury. However, knowledge on the underlying signaling events remain poor. Having recent highlight of microRNAs (miRNAs) in mediating intestinal I/R injury, we hypothesized that HRS may protect intestine against I/R injury by regulating miRNAs. Method: Mice were given intraperitoneal injection of saline or HRS once daily for five consecutive days before undergoing intestinal I/R that was induced by 60-min ischemia followed by 180-min reperfusion of superior mesenteric artery. The intestine was collected for histopathological assay, miRNA microarray profiling, Real-Time PCR, and Western blotting. Next, miR-199a-3p mimics or inhibitors were transfected into IEC-6 cells to explore the relationship between HRS treatment and miR-199a-3p. Results: I/R-induced mucosal injury and epithelial cells apoptosis were attenuated by HRS pretreatment. A total of 64 intestinal I/R-responsive miRNAs were altered significantly by HRS pretreatment, in which we validated four novel miRNAs with top significance by was drastically increased by I/R but reduced by HRS. Computational analysis predicts insulin-like growth factor (IGF)-1, mammalian target of rapamycin (mTOR), and phosphoinositide-3-kinase (PI3K) regulatory subunit 1 as targets of miR-199a-3p, suggesting involvement of the pro-survival pathway, IGF-1/PI3K/Akt/mTOR. In in vitro experiment, HRS treatment reduced miR-199a-3p level, increase IGF-1, PI3K and mTOR mRNA expression, restore IEC-6 cells viability, and this protective effects were reversed under miR-199a-3p mimics treatment. Conclusion: Collectively, miR-199a-3p may serve a key role in the anti-apoptotic mechanism of HRS that contributes to its protection of the intestine against I/R injury.

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“…Moreover, MMP23B is regulated by EPAS1 and ssc-miR-296-3p. Studies have shown that miR-296 can regulate angiogenesis [66,67].…”

Section: Discussionmentioning

confidence: 99%

KLF4, a Key Regulator of a Transitive Triplet, Acts on the TGF-β Signaling Pathway and Contributes to High-Altitude Adaptation of Tibetan Pigs

Wang

Guo

Liu

et al. 2020

Preprint

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Background: Tibetan pigs are native mammalian species on the Tibetan Plateau that have evolved distinct physiological traits that allow them to tolerate high-altitude hypoxic environments. They can be used as a suitable animal model for exploring the molecular mechanism of hypoxia adaptation in high-altitude organisms.Results: Here, based on multi-tissue transcriptional data from high-altitude Tibetan pigs and low-altitude Rongchang pigs, we performed a weighted correlation network analysis (WGCNA) and identified key modules related to these tissues. Complex network analysis and bioinformatics analysis were integrated to identify key genes and size-3 network motifs. The results showed that compared to other tissues, the lungs of Tibetan pigs and Rongchang pigs are more significantly different, showing more adaptive transcriptional changes. In the lung tissues of Tibetan pigs, we identified KLF4, BCL6B, EGR1, EPAS1, SMAD6, SMAD7, KDR, ATOH8 and CCN1 genes as potential regulators of hypoxia adaption. We found that KLF4 and EGR1 genes simultaneously regulate the BCL6B gene, forming a KLF4-EGR1-BCL6B transitive triplet. This transitive triplet, dominated by KLF4, may enhance the hypoxia adaptability of Tibetan pigs by mediating the TGF-β signaling pathway. This triplet also regulates the KDR gene, which is involved in the PI3K-Akt signaling pathway and plays an important role in hypoxia adaptation. Conclusions: We postulate that the KLF4-EGR1-BCL6B transitive triplet may contribute to the adaptation of Tibetan pigs to hypoxic environments. These findings provide new details of the regulatory architecture of hypoxia-adaptive genes and are valuable for understanding the genetic mechanism of hypoxic adaptation in mammals.

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MicroRNA-296: a promising target in the pathogenesis of atherosclerosis?

Cited by 36 publications

References 61 publications

miR‑296‑3p targets APEX1 to suppress cell migration and invasion of non‑small‑cell lung cancer

miR‑296‑3p targets APEX1 to suppress cell migration and invasion of non‑small‑cell lung cancer

MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline

KLF4, a Key Regulator of a Transitive Triplet, Acts on the TGF-β Signaling Pathway and Contributes to High-Altitude Adaptation of Tibetan Pigs

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