Transcriptome-wide map of m6A circRNAs identified in a rat model of hypoxia mediated pulmonary hypertension

Abstract

Background: Hypoxia mediated pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m 6 A-modified. The abundance of circRNAs was influenced by m 6 A. Furthermore, the significance of m 6 A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m 6 A circRNAs in HPH. Results: Differentially expressed m 6 A abundance was detected in lungs of HPH rats. M 6 A abundance in circRNAs was significantly reduced in hypoxia in vitro . M 6 A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m 6 A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M 6 A circXpo6 and m 6 A circTmtc3 were firstly identified to be downregulated in HPH. Conclusion: Our study firstly identified the transcriptome-wide map of m 6 A circRNAs in HPH. M 6 A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m 6 A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m 6 A circRNAs for HPH should be further validated. Key words: m 6 A circRNAs; hypoxia mediated pulmonary hypertension; m 6 A circXpo6; m 6 A circTmtc3

Downregulation of m6A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer

“…Several studies have revealed that m 6 A modification is involved in different diseases, including pulmonary hypertension, rheumatoid arthritis, type 2 diabetes and acute myeloid leukemia 17–20 . Moreover, further studies on the biological functions of m 6 A modification related protein in lung cancer have been reported in recent years.…”

“…Several studies have revealed that m 6 A modification is involved in different diseases, including pulmonary hypertension, rheumatoid arthritis, type 2 diabetes and acute myeloid leukemia. [17][18][19][20] Moreover, further studies on the biological functions of m 6 A modification related protein in lung cancer have been reported in recent years. For example, m 6 A demethylase ALKBH5 (m 6 A eraser) has been shown to inhibit tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibit miR-107/ LATS2-mediated YAP activity in NSCLC.…”

The critical roles of m6A modification in metabolic abnormality and cardiovascular diseases

“…Hypertension is a major risk factor for CVD, and researchers have recently disclosed that epitranscriptomic mechanism of m6A plays a critical role in hypertension. 48 The global level of m6A methylation is reduced in spontaneously hypertensive rat pericytes 49 and hypoxia mediated pulmonary hypertension, 50 and the m6A is distributed mainly in the coding sequence region, 3′UTR and 5′UTR of mRNAs. 49 m6A circXpo6 and m6A circTmtc3 are downregulated in pulmonary hypertension, moreover, m6A connects with circRNA-miRNA-mRNA network to affect the development of pulmonary hypertension.…”

The Role of N6-Methyladenosine Modified Circular RNA in Pathophysiological Processes

“…Overexpression of hsa_circ_0029589 or inhibition of METTL3 can significantly increase the expression of hsa_circ_0029589 and reduce macrophage apoptosis [146]. Increased m 6 A abundance in hypoxia mediated pulmonary hypertension (HPH) reduces the total circRNAs abundance in hypoxia in vitro [147]. M 6 A affects the co-expression network of circRNA-siRNA-mRNA during hypoxia.…”