Wang Yan, Gao Jie, Zhang Liang, Yang Rui, Zhang Yingying, Shan Liya, Li Xinzhi, Ma Ketao
Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, China.
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China.
Front Cardiovasc Med. 2023 Jun 15;10:1155767. doi: 10.3389/fcvm.2023.1155767. eCollection 2023.
Here, we aimed to investigate long non-coding RNA (lncRNA) expression characteristics in the peripheral blood lymphocytes of Xinjiang Kazakh people with essential hypertension and the underlying regulatory mechanisms of competing endogenous RNAs (ceRNA).
From April 2016 to May 2019, six Kazakh patients with essential hypertension and six Kazakh healthy participants were randomly selected from the inpatient and outpatient cardiology departments of the First Affiliated Hospital of Shihezi University Medical College, Xinjiang. After detecting the expression levels of lncRNA and mRNA in the peripheral blood lymphocytes using gene chip technology, their levels in the hypertensive group were compared with those in the control group. Six differentially expressed lncRNAs were randomly selected for real-time PCR to verify the accuracy and reliability of the gene chip results. GO functional clustering and KEGG pathway analyses were performed for differentially expressed genes. The ceRNA regulatory network of lncRNA-miRNA-mRNA was constructed, followed by visualization of the results. The expressions of miR-139-5p and DCBLD2 after PVT1 overexpression in 293T cells were detected by qRT-PCR and Western blot.
In the test group, 396 and 511 differentially expressed lncRNAs and mRNAs, respectively, were screened out. The trend of real-time PCR results was consistent with that of the microarray results. The differentially expressed mRNAs were found to be primarily involved in the adhesion spot, leukocyte migration via endothelial cells, gap junction, actin cytoskeleton regulation, and extracellular matrix-receptor interaction signaling pathways. By constructing the ceRNA regulatory network, we found that lncRNA PVT1-miR-139-5p-DCBLD2 has a potential ceRNA regulatory mechanism involved in the development of essential hypertension in Xinjiang Kazakh people. In 293T cells, lncRNA PVT1 overexpression inhibited miR-139-5p and DCBLD2 levels.
Our findings indicate that differentially expressed lncRNAs may be involved in the development of essential hypertension. lncRNA PVT1-miR-139-5p-DCBLD2 was indicated to comprise a potential ceRNA regulatory mechanism involved in the development of essential hypertension in the Xinjiang Kazakh population. Thus, it may act as a novel screening marker or therapeutic target for essential hypertension in this population.
本研究旨在探讨新疆哈萨克族原发性高血压患者外周血淋巴细胞中长链非编码RNA（lncRNA）的表达特征及竞争性内源RNA（ceRNA）的潜在调控机制。
2016年4月至2019年5月，从新疆石河子大学医学院第一附属医院心内科住院部及门诊随机选取6例哈萨克族原发性高血压患者和6例哈萨克族健康参与者。采用基因芯片技术检测外周血淋巴细胞中lncRNA和mRNA的表达水平，并将高血压组与对照组进行比较。随机选取6个差异表达的lncRNA进行实时荧光定量PCR，验证基因芯片结果的准确性和可靠性。对差异表达基因进行GO功能聚类和KEGG通路分析。构建lncRNA-miRNA-mRNA的ceRNA调控网络，并对结果进行可视化。通过qRT-PCR和蛋白质免疫印迹法检测293T细胞中PVT1过表达后miR-139-5p和DCBLD2的表达。
在试验组中，分别筛选出396个和511个差异表达的lncRNA和mRNA。实时荧光定量PCR结果趋势与基因芯片结果一致。差异表达的mRNA主要参与黏着斑、白细胞通过内皮细胞迁移、缝隙连接、肌动蛋白细胞骨架调节和细胞外基质-受体相互作用信号通路。通过构建ceRNA调控网络，发现lncRNA PVT1-miR-139-5p-DCBLD2存在一种潜在的ceRNA调控机制，参与新疆哈萨克族原发性高血压的发生发展。在293T细胞中，lncRNA PVT1过表达抑制了miR-139-5p和DCBLD2的水平。
我们的研究结果表明，差异表达的lncRNA可能参与原发性高血压的发生发展。lncRNA PVT1-miR-139-5q-DCBLD2被证实存在一种潜在的ceRNA调控机制，参与新疆哈萨克族人群原发性高血压的发生发展。因此，它可能成为该人群原发性高血压的新型筛查标志物或治疗靶点。
