lncRNA 430945 promotes the proliferation and migration of vascular smooth muscle cells via the ROR2/RhoA signaling pathway in atherosclerosis

Cui,Chuan; Wang,Xing; Shang,Xiao‑Ming; Li,Li; Ma,Yi; Zhao,Guo‑Yu; Song,Yu‑Xin; Geng,Xue‑Bin; Zhao,Bi‑Qiong; Tian,Mei‑Rong; Wang,Hong‑Ling

doi:10.3892/mmr.2019.10137

lncRNA 430945 promotes the proliferation and migration of vascular smooth muscle cells via the ROR2/RhoA signaling pathway in atherosclerosis

Authors:
- Chuan Cui
- Xing Wang
- Xiao‑Ming Shang
- Li Li
- Yi Ma
- Guo‑Yu Zhao
- Yu‑Xin Song
- Xue‑Bin Geng
- Bi‑Qiong Zhao
- Mei‑Rong Tian
- Hong‑Ling Wang
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Affiliations: Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Internal Medicine, Qian'an Hospital of Traditional Chinese Medicine, Qian'an, Hebei 064400, P.R. China, Department of Cardiology, Tangshan Workers Hospital, Tangshan, Hebei 063000, P.R. China
Published online on: April 5, 2019 https://doi.org/10.3892/mmr.2019.10137
Pages: 4663-4672
Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The proliferation and migration of vascular smooth muscle cells (VSMCs) are major cellular events in hypertension‑induced vascular remodeling, which is closely involved in the progression of atherosclerosis (AS). Although long non‑coding RNAs (lncRNAs) are gaining recognition as novel regulators of VSMCs, their functioning and role in AS remain to be elucidated. In the present study, the role of lncRNA ENST00000430945 (lncRNA 430945) in AS was investigated. VSMCs transfected with a small interfering RNA (siRNA; si‑430945) and a negative control (si‑NC) were used. Cell Counting Kit‑8, wound‑healing and Transwell migration arrays were performed to determine whether lncRNA 430945 influenced VSMC proliferation and migration. Furthermore, the study examined whether a correlation exists between lncRNA 430945 and the receptor tyrosine kinase‑like orphan receptor 2 (ROR2) signaling pathway. It was found that the expression of lncRNA 430945 was high in human AS tissues, which in turn promoted angiotensin II (AngII)‑induced VSMC proliferation. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses showed that lncRNA 430945 mediated the AngII‑induced upregulation of ROR2. In addition, the microarray and RT‑qPCR results showed that the expression of lncRNA 430945 was increased considerably in AS tissues. The downregulation of lncRNA 430945 significantly suppressed AngII‑induced VSMC proliferation and migration. In addition, ROR2 levels in VSMCs transfected with si‑430945 were markedly lower than those cells transfected with si‑NC. Additionally, western blotting showed that lncRNA 430945 activated the signaling pathways associated with ROR2 and Ras homolog gene family member A (RhoA). The upregulation of lncRNA 430945 in AS promoted the proliferation and migration of VSMCs via activation of the ROR2/RhoA signaling pathway. Therefore, targeting ROR2 or RhoA may be a promising technique in developing therapeutic strategies for treating AS.

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