LncRNA HOXA-AS2 represses endothelium inflammation by regulating the activity of NF-κB signaling

Zhu, Xinxing; Li, Yanli; Yu, Jinjin; Du, Jinyan; Guo, Rui; Feng, Yanyan; Zhong, Genshen; Jiang, Yi‐Zhou; Lin, Juntang

doi:10.1016/j.atherosclerosis.2018.12.012

Cited by 33 publications

(28 citation statements)

References 44 publications

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“…HOXA‐AS2 is a lncRNA closely linked to the evolution of cancers, which has been diffusely attested to mediate cell survival, differentiation and metastasis. [ 20,21 ] Literature from Zhu et al [ 22 ] represented that HOXA‐AS2 could dampen endothelium inflammation via activating the NF‐κB pathway. But, in sepsis‐triggered AKI, whether HOXA‐AS2 exerts a certain extent function is still not well known.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA HOXA‐AS2 mediates microRNA‐106b‐5p to repress sepsis‐engendered acute kidney injury

Wu¹,

Wang

2020

J Biochem & Molecular Tox

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HOXA cluster antisense RNA 2 (HOXA‐AS2) is a long noncoding RNA associated with the development of numerous cancers. But, whether HOXA‐AS2 exhibits a certain function in sepsis‐engendered acute kidney injury (AKI) remains uninvestigated. We strived to unveil the role of HOXA‐AS2 in sepsis‐engendered AKI. The expression of HOXA‐AS2 in sepsis patients, animal models and lipopolysaccharide (LPS)‐impaired HK‐2 cells was primarily assessed via a real‐time quantitative polymerase chain reaction. The effects of HOXA‐AS2 on cell survival of HK‐2 cells under LPS irritation were evaluated after overexpression of HOXA‐AS2. The correlation between HOXA‐AS2 and microRNA (miR)‐106b‐5p was forecasted via bioinformatics software and verified by using a luciferase report system. Subsequently, the functions of miR‐106b‐5p in LPS‐damaged HK‐2 cells were reassessed. Western blot was used for the determination of Wnt/β‐catenin and nuclear factor‐κB (NF‐κB) pathways. HOXA‐AS2 expression was decreased in sepsis patients, animal operation group and LPS‐irritated HK‐2 cells. Overexpressed HOXA‐AS2 mollified LPS‐triggered impairment in HK‐2 cells. In addition, a negative mediatory relation between HOXA‐AS2 and miR‐106b‐5p was predicated. Synchronously, overexpressed miR‐106b‐5p counteracted the protection of HOXA‐AS2 in LPS‐damaged HK‐2 cells. Ultimately, Wnt/β‐catenin and NF‐κB pathways were hindered by HOXA‐AS2 via targeting miR‐106b‐5p. HOXA‐AS2 exhibited protection in sepsis‐engendered AKI via targeting miR‐106b‐5p and hindering the Wnt/β‐catenin and NF‐κB pathways.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA HOXA‐AS2 mediates microRNA‐106b‐5p to repress sepsis‐engendered acute kidney injury

Wu¹,

Wang

2020

J Biochem & Molecular Tox

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“…Recent studies have demonstrated that HOXA-AS2 promotes cell proliferation, migration, and invasion in various human cancers, such as breast cancer, bladder cancer, and osteosarcoma. 16,17,32 Zhu et al 19 reported that inhibiting HOXA-AS2 could activate the nuclear factor (NF)-κB signaling pathway and induce subsequent inflammatory response in endothelial cells. HOXA-AS2 promoted the proliferation of HPMECs.…”

Section: Discussionmentioning

confidence: 99%

“…[16][17][18] Moreover, it is reported that expression of HOXA-AS2 is related to endothelium inflammation. 19 In our previous studies, we found the dysfunction of endothelial cells was involved in the pathogenesis of COPD. 20,21 However, whether HOXA-AS2 has a role in the progress of COPD by regulating the function of endothelial cells remains unclear.…”

Section: Introductionmentioning

confidence: 95%

<p>Microarray Analysis of Long Non-Coding RNAs in Lung Tissues of Patients with COPD and HOXA-AS2 Promotes HPMECs Proliferation via Notch1</p>

Zhou

Zhao

Zhou

et al. 2020

COPD

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Background and Objectives: Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of many diseases, including cancer, pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). In this study, we intended to identify the differentially expressed lncRNAs and the role of HOXA cluster antisense RNA 2 (HOXA-AS2) in patients with COPD. Methods: We analyzed lncRNA profiles of three non-COPD and seven COPD patients' lungs via microarray and then validated the expression of the top differentially expressed lncRNAs by using real-time polymerase chain reaction (PCR). To identify the mechanism of HOXA-AS2 during COPD pathogenesis and endothelial cell proliferation, we knocked down and overexpressed HOXA-AS2 with siRNA and lentivirus transfection approach in human pulmonary microvascular endothelial cells (HPMECs). Results: Among 29,150 distinct lncRNA transcripts, 353 lncRNAs were significantly (≥2-fold change and P<0.05) upregulated and 552 were downregulated in COPD patients. The fold change of HOXA-AS2 is 9.32; real-time PCR confirmed that HOXA-AS2 was downregulated in COPD patients. In in vitro experiments, cigarette smoke extract (CSE) treatment reduced the expression of HOXA-AS2 and cell proliferation of HPMECs. Knocking down HOXA-AS2 inhibited HPMECs proliferation and the expression of Notch1 in HPMECs. Overexpressing Notch1 could partly rescue the inhibition of cell viability induced by the silence of HOXA-AS2. Conclusion: Our results demonstrated that differentially expressed lncRNAs may act as potential molecular biomarkers for the diagnosis of COPD, and HOXA-AS2 was involved in the pathogenesis of COPD by regulating HPMECs proliferation via Notch1, which may provide a new approach for COPD treatment.

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“…The mechanisms for two recently described lncRNAs-HOXA-AS2 and PELATON-implicated in atherosclerosis are yet to be defined. For example, transcriptomic profiling of HUVECs with and without the expression of lncRNA HOXA-AS2 showed that HOXA-AS2 mediates expression of inflammatory factors [81]. Further experiments confirmed that HOXA-AS2 regulated endothelium inflammation by repressing NF-κB signaling.…”

Section: Uncharacterized Interactionsmentioning

confidence: 94%

“…Further experiments confirmed that HOXA-AS2 regulated endothelium inflammation by repressing NF-κB signaling. At the same time, NF-κB activity upregulated HOXA-AS2, which is likely the reason for the highly increased expression of HOXA-AS2 in human atherosclerotic plaques [81]. However, how exactly lncRNA HOXA-AS2 regulates inflammatory marker and especially the feedback loop with NF-κB is not yet known.…”

Section: Uncharacterized Interactionsmentioning

confidence: 99%

The Long Non-coding Road to Atherosclerosis

Josefs

Boon

2020

Curr Atheroscler Rep

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Purpose of Review To summarize recent insights into long non-coding RNAs (lncRNAs) involved in atherosclerosis. Because atherosclerosis is the main underlying pathology of cardiovascular diseases (CVD), the world's deadliest disease, finding novel therapeutic strategies is of high interest. Recent Findings LncRNAs can bind to proteins, DNA, and RNA regulating disease initiation and plaque growth as well as plaque stability in different cell types such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages. A number of lncRNAs have been implicated in cholesterol homeostasis and foam cell formation such as LASER, LeXis, and CHROME. Among others, MANTIS, lncRNA-CCL2, and MALAT1 were shown to be involved in vascular inflammation. Further regulations include, but are not limited to, DNA damage response in ECs, phenotypic switch of VSMCs, and various cell death mechanisms. Interestingly, some lncRNAs are closely correlated with response to statin treatment, such as NEXN-AS1 or LASER. Additionally, some lncRNAs may serve as CVD biomarkers. Summary LncRNAs are a potential novel therapeutic target to treat CVD, but research of lncRNA in atherosclerosis is still in its infancy. With increasing knowledge of the complex and diverse regulations of lncRNAs in the heterogeneous environment of atherosclerotic plaques, lncRNAs hold promise for their clinical translation in the near future.

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LncRNA HOXA-AS2 represses endothelium inflammation by regulating the activity of NF-κB signaling

Cited by 33 publications

References 44 publications

Long noncoding RNA HOXA‐AS2 mediates microRNA‐106b‐5p to repress sepsis‐engendered acute kidney injury

Long noncoding RNA HOXA‐AS2 mediates microRNA‐106b‐5p to repress sepsis‐engendered acute kidney injury

<p>Microarray Analysis of Long Non-Coding RNAs in Lung Tissues of Patients with COPD and HOXA-AS2 Promotes HPMECs Proliferation via Notch1</p>

The Long Non-coding Road to Atherosclerosis

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