Circular RNA hsa_circ_0016070 Is Associated with Pulmonary Arterial Hypertension by Promoting PASMC Proliferation

Abstract

Noncoding RNAs play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). In this study, we investigated the roles of hsa_circ_0016070, miR-942, and CCND1 in PAH. circRNA microarray was used to search circRNAs involved in PAH, whereas real-time PCR and western blot analysis were performed to detect miR-942 and CCND1 expression in different groups. In addition, the effect of miR-942 on CCND1 expression, as well as the effect of hsa_circ_0016070 on the expression of miR-942 and CCND1, was also studied using real-time PCR and western blot analysis. Moreover, MTT assay and flow cytometry were used to detect the effect of hsa _circ_0016070 on cell proliferation and cell cycle. According to the results of circRNA microarray analysis, hsa _circ_0016070 was identified to be associated with the risk of PAH in chronic obstructive pulmonary disease (COPD) patients. The miR-942 level in the COPD(+) PAH(+) group was much lower than that in the COPD(+) PAH(−) group, while the CCND1 level in the COPD(+) PAH(+) group was much higher. CCND1 was identified as a candidate target gene of miR-942, and the luciferase assay showed that the luciferase activity of wild-type CCND1 3′ UTR was inhibited by miR-942 mimics. In addition, hsa _circ_0016070 reduced miR-942 expression and enhanced CCND1 expression. Furthermore, hsa _circ_0016070 evidently increased cell viability and decreased the number of cells arrested in the G1/G0 phase. In summary, the results of this study suggested that hsa_circ_0016070 was associated with vascular remodeling in PAH by promoting the proliferation of pulmonary artery smooth muscle cells (PASMCs) via the miR-942/CCND1. Accordingly, has_circ_0016070 might be used as a novel biomarker in the diagnosis and treatment of PAH.

Circular RNA circ_0010283 regulates the viability and migration of oxidized low‑density lipoprotein‑induced vascular smooth muscle cells via an miR‑370‑3p/HMGB1 axis in atherosclerosis

“…Zhou et al (9) have demonstrated that circRNA HEcT domain-containing E3 ubiquitin protein ligase 1 (HEcTd1) mediates silica-induced macrophage activation by regulating the circHEcTd1/HEcTd1 axis and zinc finger cccH-type containing 12A-dependent ubiquitination process. Zhou et al (10) have reported that circular RNA hsa_circ_0016070 is associated with pulmonary arterial hypertension. In addition, circRNA antisense non-coding RNA in the INK4 locus and circRNA checkpoint with forkhead and ring finger domains (circcHFR) have been confirmed to modulate the progression of atherosclerosis (11,12).…”

“…circular RNAs (circRNAs) are a type of single-stranded RNAs with a covalently closed continuous loop that are produced by backsplicing (6) and are resistant to exonuclease-mediated degradation (7). Numerous studies have demonstrated that circRNAs are associated with cardiac repair (8), silica-induced macrophage activation (9), pulmonary arterial hypertension (10) and atherosclerosis (11). Microarray analysis has revealed that circ_0010283 is upregulated in oxidized low-density lipoprotein (ox-LdL)-induced VSMcs (12).…”

CircRNA Expression Profile in Lung Cancer Complicated with Chronic Obstructive Pulmonary Disease Patients

“…Overexpression of Circ_0078767 signi cantly repressed the proliferation of NSCLC cells [17]. CircRNA hsa_circ_0016070 was reported to promote the proliferation of pulmonary artery smooth muscle cells [15]. CircARHGAP10 suppresses NSCLC progression by promoting GLUT1 expression via sponging miR-150-5p [18].…”

“…Circular RNAs (circRNAs) is an endogenous non-coding RNA, forms a closed continuous loop by back splicing with covalently joined between 3' and 5' ends [10]. Accumulating researchers reveal the critical role of circRNAs in multiple biological processes [11] and diseases [12,13], including cancer and COPD [14][15][16]. The anomalously expressed circRNAs might provide new diagnose biomarker and therapeutic targets in diseases.…”

<p>Knockdown of hsa_circ_0059955 Induces Apoptosis and Cell Cycle Arrest in Nucleus Pulposus Cells via Inhibiting <em>Itchy E3 Ubiquitin Protein Ligase</em></p>

“…11 Due to the circular structure, circRNAs are highly conserved and stable than linear mRNAs. 12 CircRNAs are mainly located in the cytoplasm, 13 and most of the circRNAs are generated from one or more coding exons via a backsplice mechanism. 11 CircRNAs could promote gene transcription, and function as modifiers of parental gene expression.…”