Circ- calm4 Serves as an miR-337-3p Sponge to Regulate Myo10 (Myosin 10) and Promote Pulmonary Artery Smooth Muscle Proliferation

Abstract

Pulmonary artery smooth muscle cell proliferation is the pathological basis of pulmonary vascular remodeling in hypoxic pulmonary hypertension. Recent studies suggest that circular RNA (circRNA) can regulate various biological processes, including cell proliferation. Therefore, it is possible that circRNA may have important roles in pulmonary artery smooth muscle cell proliferation in hypoxic pulmonary hypertension. In the present study, we aimed to identify functional circRNAs and clarify their roles and mechanisms in pulmonary artery smooth muscle cell proliferation in pulmonary hypertension. RNA sequencing identified 67 circRNAs that were differentially expressed in hypoxic lung tissues of mice. Screening by bioinformatics and quantitative polymerase chain reaction revealed significant elevation of a circRNA derived from alternative splicing of the calmodulin 4 gene (designated circ- calm4 ). Notably, this circRNA absorbed miR-337-3p . We further identified Myo10 (myosin 10) as a target protein of miR-337-3p . miR-337-3p bound to the 3′-untranslated region of Myo10 mRNA, thereby attenuating the translation of Myo10. Using loss-of-function and gain-of-function approaches, we found that circ- calm4 regulated cell proliferation by regulating the cell cycle. Additionally, we verified the functions of miR-337-3p and Myo10 in hypoxic pulmonary artery smooth muscle. Our results suggested that the circ- calm4 / miR-337-3p /Myo10 signal transduction axis modulated the proliferation of pulmonary artery smooth muscle cells at the molecular level, thus establishing potential targets for the early diagnosis and treatment of pulmonary hypertension.

Hsa_circ_0002062 Promotes the Proliferation of Pulmonary Artery Smooth Muscle Cells by Regulating the Hsa-miR-942-5p/CDK6 Signaling Pathway

“…CircRNAs, as a recent identified member of the non-coding RNA family, will be a promising diagnostic and therapeutic target in PH ( Gokool et al, 2020 ). A series of cirRNAs have been found to participate in the development of PH, but only a few of them are clearly understood in terms of their distinct pathophysiological mechanisms ( Zhang et al, 2020 ). In order to better understand the in-depth mechanisms behind the pathogenesis of PH, we designed this study with the aim of investigating the roles of hsa_circ_0002062 in the viability and migration of hypoxic PASMCs via hsa-miR-942-5P-mediated regulation of CDK6.…”

WITHDRAWN: Identification of Non-coding RNA Biomarkers in Stress-induced Depression via Comprehensive Analysis of Competing Endogenous RNA Network

“…Increasing evidences showed that circRNA functioned as miRNA sponge to promote the activity of mRNA [19][20][21]. Recently, researchers have focused on circRNA-miRNA-mRNA, as a novel regulatory mechanism of competing endogenous RNA (ceRNA), aiming at understanding RNA interactions deeply [22].…”

BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs

“…The chopped tissues were digested for two hours in 2 mg/ml collagenase II (Sigma, c6885). PASMCs were cultured in culture medium containing 20% fetal bovine serum 63 and 1% penicillin and streptomycin in a 5% CO 2 humidified incubator at 37°C. Before each experiment, the cells were incubated in DMEM 5% serum for 24 h. Cells in hypoxic culture were incubated in a Tri-Gas Incubator (Heal Force, Shanghai, China) with a gas mixture containing 92% N2-5% CO 2 -3% O 2 for 24 h.…”