CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC

Congrains, Ada; Kamide, Kei; Katsuya, Tomohiro; Yasuda, Osamu; Oguro, Ryousuke; Yamamoto, Kōichi; Ohishi, Mitsuru; Rakugi, Hiromi

doi:10.1016/j.bbrc.2012.02.050

Cited by 121 publications

(95 citation statements)

References 39 publications

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“…Several previous reports have established that ANRIL has a regulatory effect on its neighbours CDKN2A/B (20,21,34); however, there is also evidence that ANRIL acts on certain genes that do not appear to be downstream to CDKN2A/B (35,36), reflecting a very complex regulatory panorama for this lncRNA. To investigate the downstream molecular events involving ANRIL and SOC invasiveness and/or metastasis in the current study, we compared SK-OV-3.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Qiu

Lin

Ding

et al. 2015

International Journal of Oncology

122

103

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Abstract. Recent studies have highlighted the role of long non-coding RNAs (lncRNAs) in carcinogenesis and have suggested that genes of this class might be used as biomarkers in cancer. However, whether lncRNAs are involved in serous ovarian cancer (SOC) remains largely unknown. In the present study, we focused on lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) and investigated its expression pattern, clinical significance, and biological function in SOC. We found that ANRIL levels were elevated in SOC tissues compared with normal controls and were highly correlated with advanced FIGO stage, high histological grade, lymph node metastasis, and poor prognosis. Multivariate analysis further revealed that ANRIL is an independent prognostic factor for predicting overall survival of SOC patients. In vitro, we compared differential ANRIL levels between SOC parental cell lines (SK-OV-3, HO8910) and highly metastatic sublines (SK-OV-3.ip1, HO8910-PM). Notably, ANRIL was highly expressed in both SK-OV-3.ip1 cells and HO8910-PM cells. SiRNA-mediated ANRIL silencing in these cells impaired cell migration and invasion. Based on the metastasis-related mRNA microarray analysis and subsequent western blotting confirmation, we found that MET and MMP3 are key downstream genes of ANRIL involved in SOC cell migration/ invasion. Together, our data suggest that lncRNA ANRIL plays an important role in SOC invasion/metastasis and could represent a novel biomarker for predicting poor survival as well a promising therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Qiu

Lin

Ding

et al. 2015

International Journal of Oncology

122

103

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“…However, very different effects can be seen in other cell types (349). Furthermore, ANRIL expression can affect the expression of numerous other genes that may be involved in atherogenesis (347). This findings and the fact that mice do not have a locus entirely orthologous to ANRIL make many animal studies difficult to interpret.…”

Section: Control Of Proliferation: Relationship To Atherosclerosismentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

388

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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“…Early studies identified antisense noncoding RNA in the INK4 locus (ANRIL), a lncRNA expressed in VSMC, which was able to regulate CDKN2A/B expression in aortic VSMC and attenuate proliferation in atherosclerosis [64][65][66] as well as modulate inflammatory responses in coronary artery disease [67].…”

Section: Role Of Lncrnas In Vascular Remodellingmentioning

confidence: 99%

Role of noncoding RNA in vascular remodelling

Lin

Bradshaw

Baker

2016

Current Opinion in Lipidology

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Purpose of review: Non-coding RNA (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (LncRNAs), are becoming fundamentally important in the pathophysiology relating to injury-induced vascular remodelling. We highlight recent studies that demonstrate the involvement of ncRNAs in vein graft disease, in in-stent restenosis (ISR) and in pulmonary arterial hypertension (PAH), with a particular focus on endothelial cell (EC) and vascular smooth muscle cell (VSMC) function. We also briefly discuss the emerging role of exosomal-derived ncRNAs and how this mechanism impacts on vascular function.

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CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC

Cited by 121 publications

References 39 publications

Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Molecular Biology of Atherosclerosis

Role of noncoding RNA in vascular remodelling

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