Identification of lncRNA-mRNA regulatory network associated with isolated systolic hypertension and atherosclerotic cerebral infarction

Fang-Xiao Hu; Jie Yang; Chuan-Hua Yang; Yan-Nan Tao; Xue-Song Yang; Ming-Ling Cui; Guan-Lan Li; Chao Li; Yue-Hua Jiang

doi:10.21037/atm-21-5176

Identification of lncRNA-mRNA regulatory network associated with isolated systolic hypertension and atherosclerotic cerebral infarction

Ann Transl Med. 2021 Oct;9(20):1589. doi: 10.21037/atm-21-5176.

Authors

Fang-Xiao Hu^#¹, Jie Yang^#^{1

2}, Chuan-Hua Yang², Yan-Nan Tao³, Xue-Song Yang⁴, Ming-Ling Cui¹, Guan-Lan Li¹, Chao Li¹, Yue-Hua Jiang⁵

Affiliations

¹ Shandong University of Traditional Chinese Medicine, Jinan, China.
² Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
³ Shandong University of Traditional Chinese Medicine Second Affiliated Hospital, Jinan, China.
⁴ Department of Vascular Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
⁵ Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

^# Contributed equally.

Abstract

Background: Increasingly, evidence has shown that long non-coding RNAs (lncRNAs) play an important role in isolated systolic hypertension (ISH). However, a systematic lncRNA-messenger RNA (mRNA) regulatory network is still absent in isolated systolic hypertension and atherosclerotic cerebral infarction patients (ISH & ACI). This research aimed to establish a lncRNA-mRNA co-expression network in patients with ISH & ACI, to probe into the potential functions of lncRNA in such patients.

Methods: Expression profiles of lncRNA and mRNAs were collected and compared, from 8 patients with ISH and 8 patients with ISH & ACI by RNA-seq data. Differentially expressed lncRNAs and mRNAs were screened out via high-throughput sequencing in the plasma of ISH/ACI patients and control ISH patients. Then, a lncRNA-mRNA interaction network was built using the Pearson correlation coefficient by Cytoscape software. The expression levels of the hub genes and lncRNAs were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in another 10 ISH/ACI patients and 10 control patients. This study was approved by the responsible institutional review board (IRB) and informed consent was provided by participants.

Results: A total of 2,768 differentially expressed lncRNAs and 747 differentially expressed mRNAs were identified. We identified two hub genes (CD226 and PARVB) and 11 lncRNAs in the lncRNA-mRNA interaction network. The results of qRT-PCR and cell assay verified that lncRNAs ENST00000590604 and CD226 are highly expressed in patients of ISH & ACI. Further, CD226 was associated with vascular endothelial cells growth and stability through the platelet activation and focal adhesion pathway.

Conclusions: We established a novel mRNA-lncRNA interaction network. The lncRNAs ENST00000590604 and CD226 might be the potential biomarkers of ISH & ACI.

Keywords: Isolated systolic hypertension (ISH); atherosclerotic cerebral infarction (ACI); heart and cerebral vessels; long non-coding RNA (lncRNA); messenger RNA (mRNA).