Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

02 August 2019 : Laboratory Research  

MicroRNA-214-3p Regulates Hypoxia-Mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration by Targeting ARHGEF12

Xi-Qian Xing1ABCDEFG, Bo Li2AB, Shuang-Lan Xu1BCD, Jie Liu1BC, Chun-Fang Zhang1F, Jiao Yang3AEG*

DOI: 10.12659/MSM.915709

Med Sci Monit 2019; 25:5738-5746

Abstract

BACKGROUND: miR-214-3p has been found to inhibit proliferation and migration in cancer cells. The objective of this study was to determine whether ARHGEF12 is involved in miR-214-3p-mediated suppression of proliferation and migration of pulmonary artery smooth muscle cells (PASMCs).

MATERIAL AND METHODS: PASMCs were cultured under normoxia or hypoxia. miR-214-3p mimics or inhibitors were transiently transfected into PASMCs. Proliferation, apoptosis, and migration of PASMCs were evaluated using MTT assay, flow cytometry, and Boyden chamber apparatus. Western blot analysis was used to examine expression of Rho guanine nucleotide exchange factor 12 (ARHGEF12), c-fos, c-jun, and caspase-3. Luciferase reporter assay was used to test the direct regulation of miR-214-3p on the 3’-untranslated region (UTR) of ARHGEF12.

RESULTS: miR-214-3p was significantly upregulated in hypoxia-treated PASMCs. Knockdown of miR-214-3p significantly attenuated hypoxia-induced proliferation and migration in PASMCs and promoted apoptosis, whereas this effect was aggravated by overexpression of miR-214-3p. In addition, dual-luciferase reporter assay demonstrated that ARHGEF12 is a direct target gene of miR-214-3p. The protein levels of ARHGEF12 were downregulated after knockdown of miR-214-3p in PASMCs. Rescue experiment results indicated that decreased proliferation of PASMCs resulted from knockdown of miR-214-3p were partially reversed by silencing of ARHGEF12 by siRNA. Furthermore, knockdown of miR-214-3p reduced expression of c-jun and c-fos, but increased expression of caspase-3 in PASMCs under hypoxia.

CONCLUSIONS: In conclusion, these results indicate that miR-214-3p acts as a novel regulator of hypoxia-induced proliferation and migration by directly targeting ARHGEF12 and dysregulating c-jun and c-fos in PASMCs, and may be a potential therapeutic target for treating pulmonary hypertension.

Keywords: Hypertension, Pulmonary, Rho Guanine Nucleotide Exchange Factors, Cell Hypoxia, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, primary cell culture, Pulmonary Artery

Add Comment 0 Comments

Editorial

01 February 2024 : Editorial  

Editorial: Global Health Concerns as Vaccine-Preventable Infections Including SARS-CoV-2 (JN.1), Influenza, Respiratory Syncytial Virus (RSV), and Measles Continue to Rise

Dinah V. Parums

DOI: 10.12659/MSM.943911

Med Sci Monit 2024; 30:e943911

0:00

In Press

01 Feb 2024 : Review article  

Review of the Evaluation of Pulmonary Hypoplasia as an Important Determinant of Clinical Outcomes in Infant...

Med Sci Monit In Press; DOI: 10.12659/MSM.943259  

0:00

19 Feb 2024 : Clinical Research  

Diagnostic Accuracy of Ileocolic Artery and Vein Diameter for Acute Appendicitis

Med Sci Monit In Press; DOI: 10.12659/MSM.943846  

23 Feb 2024 : Clinical Research  

Early Mobilization in Pediatric Critical Care: Exploring the Gap Between Theory and Practice in Saudi Arabia

Med Sci Monit In Press; DOI: 10.12659/MSM.942467  

01 Feb 2024 : Review article  

Enhancing Patient Adherence to Newly-Prescribed Medicine for Chronic Diseases: A Comprehensive Review and C...

Med Sci Monit In Press; DOI: 10.12659/MSM.942923  

Most Viewed Current Articles

16 May 2023 : Clinical Research  

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

17 Jan 2024 : Review article  

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750