The Role of the miR-548au-3p/CA12 Axis in Tracheal Chondrogenesis in Congenital Pulmonary Airway Malformations. (17th February 2023)

• Record Type: Journal Article
• Authors: Zeng, Jiahang; Zhang, Xinwen; Yang, Qinglin; Peng, Junzheng; Wang, Fenghua; Tang, Jue; Xu, Yingyi; Huang, Dongmei; Liang, Jianhua; Li, Le
• Other Names: Muddassir Ali Muhammad Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2023(2023)
• Publication Date: 2023-02-17
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2023/6428579
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Background . Literature has identified differentially expressed miRNAs in congenital pulmonary airway malformation (CPAM). However, the functional role of these miRNAs in CPAM remains unclear. Methods . We obtained diseased lung tissues as well as adjacent normal lung tissue from CPAM patients attending the centre. Hematoxylin and eosin (H&E) and Alcian blue staining were performed. Differentially expressed mRNA expression profile was CPAM tissue, and matched normal tissue specimens were examined by high-throughput RNA sequencing. CCK-8 assay, EdU staining, TUNEL staining, flow cytometry, and the Transwell assay were performed to investigate the effect of miR-548au-3p/CA12 axis on proliferation, apoptosis, and chondrogenic differentiation in rat tracheal chondrocytes. mRNA and protein expression levels were determined using reverse transcription-quantitative PCR and western blot analysis, respectively. The relationship between miR-548au-3p and CA12 was evaluated using the luciferase reporter assay. Results . The expression level of miR-548au-3p was significantly increased in diseased tissues compared with normal adjacent tissues from patients with CPAM. Our results indicate that miR-548au-3p functions as a positive regulator in rat tracheal chondrocyte proliferation and chondrogenic differentiation. At molecular level, miR-548au-3p promoted N-cadherin, MMP13, and ADAMTS4 expressions and reduced E-cadherin, aggrecan, and Col2A1 expressions. CA12 has been previously reported as a predicted target of miR-548au-3p, and here, we show that overexpression of CA12 in rat tracheal chondrocyte mimics the effects of inhibition of miR-548au-3p. On the other hand, CA12 knockdown reversed the effects of miR-548au-3p on cell proliferation, apoptosis, and chondrogenic differentiation. Conclusions . In conclusion, the miR-548au-3p/CA12 axis plays a role in the pathogenesis of CPAM and may lead to identification of new approaches for CPAM treatment.