NORAD affects the progression of diabetic nephropathy through targeting miR-520h to upregulate TLR4

Qi, Huimeng; Li, Yao; Liu, Qiang

doi:10.1016/j.bbrc.2019.10.102

Cited by 12 publications

(11 citation statements)

References 23 publications

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“…In the present study, NORAD knockdown suppressed HG-stimulated HMC proliferation, inflammation and fibrosis. Similar to the results of the present study, a recent study also demonstrated that knockdown of NORAD decreased cell viability in mouse glomerular mesangial cells in DN (17). However, the previous study only investigated the mechanism of NORAD on cell proliferation.…”

Section: Discussionsupporting

confidence: 90%

“…NORAD has been demonstrated to be an onco-lncRNA in various types of human cancer, including prostate (13), ovarian (14), lung (15) and gastric (16) cancers. lncRNA NORAD is also involved in DN progression (17). Qi et al (17) demonstrated that the NORAD/miR-520h/Toll-like receptor 4 regulatory loop promotes the proliferation and inhibits the apoptosis of glomerular MCs, thereby aggravating the progression of DN.…”

Section: Introductionmentioning

confidence: 99%

“…lncRNA NORAD is also involved in DN progression (17). Qi et al (17) demonstrated that the NORAD/miR-520h/Toll-like receptor 4 regulatory loop promotes the proliferation and inhibits the apoptosis of glomerular MCs, thereby aggravating the progression of DN. However, the possible effects of NORAD on the inflammation and fibrosis of DN and the underlying regulatory mechanisms remain to be fully revealed.…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis

et al. 2021

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Long non-coding RNAs (lncRNAs) serve major roles in diabetic nephropathy (DN). The present study investigated the regulatory mechanism of lncRNA non-coding RNA activated by DNA damage (NORAD) on DN in vitro. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of lncRNA NORAD, microRNA-485 (miR-485) and nuclear respiratory factor 1 (NRF1) in the tissues of patients with DN and high-glucose (HG)-induced human mesangial cells (HMCs). The viability of HMCs was determined using an MTT assay. The levels of inflammatory [tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6] and fibrotic [type IV collagen (Col. IV), fibronectin (FN) and plasminogen activator inhibitor 1 (PAI-1)] factors in HMCs were measured by ELISA. The interactions between miR-485 and NORAD/NRF1 were predicted using StarBase and miRDB softwares and confirmed by a dual-luciferase reporter assay. Western blot analysis was utilized to measure NRF1 protein levels. lncRNA NORAD was highly expressed in tissues and HG-induced HMCs. NORAD knockdown suppressed cell viability in HG-induced HMCs. The levels of the inflammatory and fibrotic factors in HG-induced HMCs were inhibited by NORAD knockdown. miR-485 was the direct target of NORAD. NORAD reversed the inhibitory effects of miR-485 on HG-induced HMCs. Furthermore, NRF1 was the target gene of miR-485. Downregulation of miR-485 and upregulation of NRF1 reversed the inhibitory effects of NORAD knockdown on HG-induced HMCs. NORAD knockdown inhibited HG-induced HMC proliferation, inflammation and fibrosis by regulating miR-485/NRF1, providing a possible therapeutic strategy for DN.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis

et al. 2021

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“…Moreover, lncRNA NORAD increases the sensitivity of osteosarcoma to cisplatin through targeting miR-410-3p (Xie et al, 2020). In addition, lncRNA NORAD upregulates TLR4 expression via targeting miR-520h to promote the progression of diabetic nephropathy (Qi et al, 2020). Besides, lncRNA NORAD also exerts decoy function by sequestering target proteins to regulate genomic stability or cancer metastasis (Lee et al, 2016;Tan et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6

Kai

Yin

et al. 2021

Front. Cell Dev. Biol.

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Coronary artery disease (CAD) is a major atherosclerotic cardiovascular disease and the leading cause of mortality globally. Long non-coding RNAs (lncRNAs) play crucial roles in CAD development. To date, the effect of lncRNA non-coding RNA activated by DNA damage (NORAD) on atherosclerosis in CAD remains unclear. The primary aim of this study was to investigate the effect of lncRNA NORAD on vascular endothelial cell injury and atherosclerosis. Here, ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and high-fat-diet (HFD)-fed ApoE–/– mice were utilized as in vitro and in vivo models. The present study found that lncRNA NORAD expression was increased in ox-LDL-treated HUVECs and thoracic aorta of atherosclerotic mice, and knockdown of lncRNA NORAD alleviated vascular endothelial cell injury and atherosclerosis development in vitro and in vivo. Knockdown of lncRNA NORAD aggravated ox-LDL-reduced or atherosclerosis-decreased vascular endothelial growth factor (VEGF) expression in HUVECs and thoracic aorta of mice to ameliorate vascular endothelial cell injury and atherosclerosis development. Moreover, nucleus lncRNA NORAD suppressed VEGF gene transcription through enhancing H3K9 deacetylation via recruiting HDAC6 to the VEGF gene promoter in ox-LDL-treated HUVECs. In addition, VEGF reduced FUS (FUS RNA binding protein) expression by a negative feedback regulation in HUVECs. In summary, lncRNA NORAD enhanced vascular endothelial cell injury and atherosclerosis through suppressing VEGF gene transcription via enhancing H3K9 deacetylation by recruiting HDAC6. The findings could facilitate discovering novel diagnostic markers and therapeutic targets for CAD.

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“…Zhou et al found that high expression of NORAD promoted breast cancer progression through regulating TGF-β pathway and had a poor prognosis [30]. Moreover, upregulation of NORAD was demonstrated to affect the progression of diabetic nephropathy through targeting miR-520 h to increase the expression of TLR4 [31]. What's more, NORAD had been demonstrated to enhance the proliferation and migration of PC cells and suppressed their apoptosis in PC [20].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NORAD contributes to the proliferation, invasion and EMT progression of prostate cancer via the miR-30a-5p/RAB11A/WNT/β-catenin pathway

Zhang

2020

Cancer Cell Int

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Background Prostate cancer (PC) is common male cancer with high mortality worldwide. Emerging evidence demonstrated that long noncoding RNAs (lncRNAs) play critical roles in various type of cancers including PC by serving as competing endogenous RNAs (ceRNAs) to modulate microRNAs (miRNAs). LncRNA activated by DNA damage (NORAD) was found to be upregulated in PC cells, while the detailed function and regulatory mechanism of NORAD in PC progression remains largely unclear. Methods Expression of NORAD in PC tissues and cell lines were detected by real-time quantitative PCR (qRT-PCR). NORAD was respectively overexpressed and knocked down by transfection with pcDNA-NORAD and NORAD siRNA into PC-3 and LNCap cells. Cell proliferation, invasion and apoptosis were determined by using CCK-8, Transwell and Flow cytometry assays, respectively. The target correlations between miR-30-5p and NORAD or RAB11A were confirmed by using dual luciferase reporter assay. Moreover, expression levels of RAB11A, the epithelial-mesenchymal transition (EMT) marker proteins and the Wnt pathway related proteins were measured by Western blotting. Tumor xenograft assay was used to study the effect of NORAD on tumor growth in vivo. Results NORAD was upregulated in PC tissues and cells. Overexpression of NORAD promoted cell proliferation, invasion, EMT, and inhibited cell apoptosis; while knockdown of NORAD had the opposite effect. NORAD was found to be functioned as a ceRNA to bind and downregulated miR-30a-5p that was downregulated in PC tumor tissues. Rescue experiments revealed that miR-30a-5p could weaken the NORAD-mediated promoting effects on cell proliferation, invasion and EMT. Furthermore, RAB11A that belongs to a member of RAS oncogene family was verified as a target of miR-30a-5p, and reintroduction of RAB11A attenuated the effects of miR-30a-5p overexpression on cell proliferation, invasion, EMT and apoptosis of PC cells. More importantly, silencing RAB11A partially reversed the promoting effects of NORAD overexpression on cell proliferation, invasion and EMT of PC cells via the WNT/β-catenin pathway. Lastly, tumorigenicity assay in vivo demonstrated that NORAD increased tumor volume and weight via miR-30a-5p /RAB11A pathway. Conclusion Our results indicated a significant role of NORAD in mechanisms associated with PC progression. NORAD promoted cell proliferation, invasion and EMT via the miR-30a-5p/RAB11A/WNT/β-catenin pathway, thus inducing PC tumor growth.

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NORAD affects the progression of diabetic nephropathy through targeting miR-520h to upregulate TLR4

Cited by 12 publications

References 23 publications

Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis

Knockdown of lncRNA NORAD inhibits the proliferation, inflammation and fibrosis of human mesangial cells under high‑glucose conditions by regulating the miR‑485/NRF1 axis

LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6

Long non-coding RNA NORAD contributes to the proliferation, invasion and EMT progression of prostate cancer via the miR-30a-5p/RAB11A/WNT/β-catenin pathway

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