Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 48, Issue 5, Pages -Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2021.5035
Keywords
circular RNA glutamate metabotropic receptor 1; pulmonary smooth muscle cells; glutamate receptor metabotropic 1; Rap1 signalling pathway; FUS RNA binding protein
Categories
Funding
- Shandong Key Research and Development Plan [2019GSF108186, 2014GSF118066]
- Shandong, China
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Circular RNA circ-Grm1 may play a role in promoting the proliferation and migration of pulmonary artery smooth muscle cells in hypoxic pulmonary hypertension by suppressing the expression of Grm1 through FUS.
Pulmonary arterial hypertension is a progressive and fatal disease. Recent studies suggest that circular RNA (circRNAs/circs) 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 (HPH). The aim of the present study was to determine the role and mechanism of circRNA-glutamate metabotropic receptor 1 (circ-Grm1; mmu_circ_0001907) in pulmonary artery smooth muscle cell (PASMC) proliferation and migration in HPH. High-throughput transcriptome sequencing was used to screen circRNAs and targeted genes involved in HPH. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2-deoxyuridine and wound healing assays were employed to assess cell viability and migration. Reverse transcription-quantitative PCR and western blotting were used to detect target gene expression in different groups. Bioinformatical approaches were used to predict the interaction probabilities of circ-Grm1 and Grm1 with FUS RNA binding protein (FUS). The interactions of circ-Grm1, Grm1 and FUS were evaluated using RNA silencing and RNA immunoprecipitation assays. The results demonstrated that circ-Grm1 was upregulated in hypoxic PASMCs. Further experiments revealed that the knockdown of circ-Grm1 could suppress the proliferation and migration of hypoxic PASMCs. Transcriptome sequencing revealed that Grm1 could be the target gene of circ-Grm1. It was found that circ-Grm1 could competitively bind to FUS and consequently downregulate Grm1. Moreover, Grm1 could inhibit the function of circ-Grm1 by promoting the proliferative and migratory abilities of hypoxic PASMCs. The results also demonstrated that circ-Grm1 influenced the biological functions of PASMCs via the Rap1/ERK pathway by regulating Grm1. Overall, the current results suggested that circ-Grm1 was associated with HPH and promoted the proliferation and migration of PASMCs via suppression of Grm1 expression through FUS.
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