Long non‑coding RNA SNHG16 inhibits the oxygen‑glucose deprivation and reoxygenation‑induced apoptosis in human brain microvascular endothelial cells by regulating miR‑15a‑5p/bcl‑2

Teng,Hongwei; Li,Ming; Qian,Lei; Yang,Hua; Pang,Mingzhi

doi:10.3892/mmr.2020.11385

Long non‑coding RNA SNHG16 inhibits the oxygen‑glucose deprivation and reoxygenation‑induced apoptosis in human brain microvascular endothelial cells by regulating miR‑15a‑5p/bcl‑2

Authors:
- Hongwei Teng
- Ming Li
- Lei Qian
- Hua Yang
- Mingzhi Pang
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Affiliations: Department of Neurosurgery, Binhai County People's Hospital, Yancheng, Jiangsu 224500, P.R. China, Department of Laboratory Medicine, Binhai County People's Hospital, Yancheng, Jiangsu 224500, P.R. China, Department of Neurosurgery, Wuxi No. 2 Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
Published online on: July 29, 2020 https://doi.org/10.3892/mmr.2020.11385
Pages: 2685-2694
Copyright: © Teng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNA (miR) 15a‑5p can promote ischemia/reperfusion (I/R)‑induced apoptosis of cerebral vascular endothelial cells, which is inhibited by long non‑coding RNAs (lncRNAs). The present study investigated the potential of lncRNAs targeting miR‑15a‑5p to regulate oxygen‑glucose deprivation and reoxygenation (OGD‑R)‑induced apoptosis of human brain microvascular endothelial cells (hBMECs). hBMECs were transfected with or without miR‑15a‑5p or its mutant, together with p‑small nucleolar RNA host gene 16 (SNHG16) or its mutant. Following OGD‑R, proliferation, apoptosis and miR‑15a‑5p, SNHG16 and Bcl‑2 expression levels were determined using MTT, flow cytometry, reverse transcription‑quantitative PCR or western blotting. The potential interaction of SNHG16 with miR‑15a‑5p was analyzed by pull‑down, luciferase and immunoprecipitation assays. OGD‑R induced apoptosis of hBMECs and increased miR‑15a‑5p expression levels in a time‑dependent manner. miR‑15a‑5p overexpression decreased the proliferation of hBMECs and promoted apoptosis by decreasing Bcl‑2 expression levels. SNHG16 was pulled‑down by miR‑15a‑5p and anti‑Ago2. miR‑15a‑5p overexpression significantly decreased SNHG16‑regulated luciferase activity and hBMEC survival by increasing apoptosis. SNHG16 overexpression decreased miR‑15a‑5p expression levels in hBMECs. SNHG16 gradually decreased following OGD‑R and its overexpression decreased miR‑15a‑5p expression levels and promoted the proliferation of hBMECs by decreasing apoptosis. SNHG16 enhanced Bcl‑2 expression levels in hBMECs, which was abrogated by miR‑15a‑5p. Bioinformatics suggest that SNHG16 may antagonize the binding of miR‑15a‑5p to the 3'UTR of Bcl‑2 mRNA. These findings suggest that SNHG16 may protect hBMECs from OGD‑R‑induced apoptosis by antagonizing the miR‑15a‑5p/bcl‑2 axis. Thus, targeting SNHG16‑based mechanisms may provide novel therapeutic strategies for treatment of ischemic stroke.

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