Construction of a ceRNA coregulatory network and screening of hub biomarkers for salt‐sensitive hypertension

Abstract

Salt‐sensitive hypertension (SSH) is an independent risk factor for cardiovascular disease. The regulation of long non‐coding RNAs, mRNAs and competing endogenous RNAs (ceRNAs) in the pathogenesis of SSH is uncertain. An RNA microarray was performed to discover SSH‐associated differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs), and 296 DElncRNAs and 44 DEmRNAs were identified, and 247 DElncRNAs and 44 DEmRNAs among these RNAs were included in the coexpression network. The coregulatory network included 23 ceRNA loops, and six hub RNAs (lnc‐ILK‐8:1, lnc‐OTX1‐7:1, lnc‐RCAN1‐6:1, GIMAP8 , SUV420H1 and PIGV ) were identified for further population validation. The ceRNA correlations among lnc‐OTX1‐7:1, hsa‐miR‐361‐5p and GIMAP8 were confirmed in SSH and SRH patients. A larger‐sample validation confirmed that GIMAP8, SUV420H1 and PIGV were differentially expressed between the SSH and SRH groups. In addition, SUV420H1 was included in the SSH screening model, and the area under the curve of the model was 0.720 (95% CI: 0.624‐0.816). Our study explored the transcriptome profiles of SSH and constructed a ceRNA network to help elucidate the mechanism of SSH. In addition, SUV420H1 was identified as a hub element that participates in SSH transcriptional regulation and as a potential biomarker for the early diagnosis of SSH.

Association of Circulating Biomarkers of lnc-IGSF3-1:1, SCOC-AS1, and SLC8A1-AS1 with Salt Sensitivity of Blood Pressure in Chinese Population

“…As salt sensitivity plays important role in the occurrence of CVDs, researchers have conducted a growing number of studies on biomarkers of SS, including metabolomics [42], genomics [15], and transcriptomics [25]. Such studies provide potential evidence for elucidating the mechanism of SS.…”

“…cgi? acc = GSE135111); more details were available in our previous study, which constructed 23 competing endogenous RNA loops of salt sensitivity in hypertensive patients [25].…”

“…Long non-coding RNA (lncRNA) is a crucial part of epigenetics and a class of non-coding RNAs that longer than 200 nucleotides [22]. Recently, accumulating evidence suggested that lncRNAs could play biological roles in SS [23][24][25] and hypertension [26][27][28][29] development. LncRNA-NONRATG012674.2 was differently expressed between SS and SR rats, and was highly correlated with BP and angiogenesis-related genes [23].…”

“…LncRNA-sONE could be a drug target in the antihypertensive process of Lycium barbarum L [24]. In human, we previously found 247 differentially expressed lncRNAs between SS and SR hypertensives, among which three lncRNAs (lnc-ILK-8:1, lnc-OTX1-7:1, and lnc-RCAN1-6:1) were identified as hub biomarkers in the competing endogenous RNA coregulatory network of saltsensitive hypertension [25]. However, studies on diagnostic lncRNAs related to SS in adults are limited.…”

Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators

“…The evaluation of SSBP was conducted by MSAOSL-DST, the details of which have been previously published ( Mu et al, 1993 ; Liu et al, 2017 , 2018 ; Zhang et al, 2020 ). Each fasting participant received an oral administration of 1,000 ml of 0.9% saline solution within 30 min and oral administration of 40 mg furosemide after 2 h of saline loading.…”