LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF‐1α/VEGF signaling in ischemic stroke
Authors: Yuanxiao Zhang
Yaru Dong
Feng Chen
Lin Zhang
Wei Yuan
Xinli Xiao
Xianliang Luo
Xiaohua Zhang
Yong Liu
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HIF-1a/VEGF; SNHG1; competing endogenous RNA; ischemic stroke; miR-18a.
Affiliations: Department of Neurology, Xi'an Central Hospital, The Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, China., Department of Medicine, Xi 'an Sixth Hospital, Xi'an, China., Department of Neurosurgery, Jinhua Central Hospital, Jinhua, China., Department of Cardiology, Xi'an North Hospital, Xi'an, China., Institute of neurobiology, Xi'an Jiaotong University Health Science Center, Xi'an, China., Department of Neurology, Xi'an Central Hospital, Xi'an, China.

Abstract:  Studies have shown that long noncoding ribonucleic acids (lncRNAs) play critical roles in multiple biologic processes. However, the Small Nucleolar RNA Host Gene 1 (SNHG1) function and underlying molecular mechanisms in ischemic stroke have not yet been reported. In the present study, we found that SNHG1 expression was remarkably increased both in isolated cerebral micro-vessels of a middle cerebral artery occlusion (MCAO) mice model, and in oxygen-glucose deprivation (OGD)-cultured mice brain micro-vascular endothelial cells (BMECs), meanwhile, the SNHG1 level was negatively correlated with miR-18a in MCAO mice. Mechanistically, SNHG1 inhibition presents larger brain infarct size and worsens neurological scores in MCAO mice. Consistent with the in vivo findings, SNHG1 inhibition also significantly increased caspase-3 activity and cell apoptosis in OGD-cultured BMECs. Furthermore, we found that SNHG1 functions as a competing endogenous RNA (ceRNA) for miR-18a, thereby regulating the de-repression of its endogenous target HIF-1α and promoting BMEC survival through HIF-1α/VEGF signaling. This study found a neuroprotective effect of SNHG1 mediated by HIF-1α/VEGF signaling through acting as a ceRNA for miR-18a. These findings reveal a novel function of SNHG1, which contributes to an extensive understanding of ischemic stroke and provides novel therapeutic options for this disease. 

Retracted: No

PubPeer comments:
 Fig 6F.  HIF-1u03b1 3u2032-UTR construct was then transfected along with miR-18a mimic and plasmid-encoding HOTAIR (pcDNA-SNHG1) or mutant SNHG1 (pcDNA vector) as a control into HEK293T cells to verify the ceRNA effect of SNHG1, confirmed by Western blot assay  . ![file] The same loading control appears in Fig 2D from [Chen, Xu Qu (2018)] . ![file] , 
 Fig 3C.  Silencing of SNHG1 promotes ischemia-induced endothelial cell death and decreased cell survival. ... Exposure to OGD leads to obvious BMEC cell death detected by ... cytometry . ![file] Two pairs of moose portraits appear to be the same across their central and lower-left - green and light-blue boxes. The dark blue box around the OGD panel is to call attention to similar panels in Fig 5D of [Zhang et al (2017)] : ![] ... and in Fig 2G of [Li et al (2018)] , and Fig 3A from [Long et al (2017)] . ![] ![] ,