Over-expression of microRNA-145 Elevating Autophagy Activities via Downregulating FRS2 Expression-Reference-Cited by-同舟云学术

Over-expression of microRNA-145 Elevating Autophagy Activities via Downregulating FRS2 Expression

Published:2024-01 Issue:1 Volume:27 Page:127-135
ISSN:1386-2073
Container-title:Combinatorial Chemistry & High Throughput Screening
language:en
Short-container-title:CCHTS

Author:

Tian Ke¹,Deng Bin²,Han Xiaodong³,Zheng Haiyi¹,Lin Tao¹,Wang Zhimeng¹,Zhang Yuanmin¹,Wang Guodong¹

Affiliation:

1. Department of Orthopedics and Joint, Affiiated Hospital of Jining Medical University, Shandong, 272001, China

2. Department of Orthopedics, Affiliated Hospital of Jining Medical University, Shandong Province, Zoucheng District, Jining, 273500, Shandong, People's Republic of China

3. Department of Orthopedics, Affiliated Hospital of Jining Medical University, Shandong Province, Zoucheng District, Jining, 273500, Shandong, People's Republic of China.

Abstract

Objectives: Osteoarthritis (OA) is one of the most common chronic and progressive joint diseases characterized by cartilage degeneration and chondrocyte death. In this study, we aimed to identify the modulation effect of miR-145 on chondrocytes' autophagy during the development of OA. Background: Osteoarthritis (OA) is one of the most prevalent types of chronic and progressive joint disorder with the symptoms of joint pain and stiffness, and it leads to disability at the end stage. In recent years, microRNA-145 (miR-145) has been found to activate autophagy in various cell types, including mesenchymal stem cells, cardiomyocytes, and osteosarcoma cells. However, it is unknown whether miR-145 regulates the progression of OA by influencing chondrocyte autophagy. Methods: Before investigating the regulatory effect of miR-145 on the autophagic activity of chondrocytes, the expression of miR-145 in human joint samples was analyzed. The targeting relationship between miR-145 and FRS2 was detected by dual luciferase assay. The effect of FRS2 and miR-145 on the autophagic activity of chondrocytes was observed by bidirectional expression of FRS2 and miR-145. Results: The miR-145 expression and LC3-II/LC3-I ratio were significantly decreased and the SQSTM1 expression was increased in OA patients. The miR-145 overexpression in C20A4 cells increased LC3-II/LC3-I ratio, decreased SQSTM1 expression, and was positively correlated with autophagic activity. Under oxidative stress, miR-145 overexpression significantly improved chondrocyte viability through autophagy stimulation. FRS2 is a potential target of miR-145 via a binding sequence within its 3’ UTR. FRS2 acts as the downstream mediator of miR-145 to suppress autophagy through activating PI3K/Akt/mTOR pathways. Conclusion: The miR-145 acts as a protective factor against chondrocytes by regulating miRFRS2- autophagy axis. The decrease of miR-145 in articular synovial fluid may turn out to be an important marker for early diagnosis of OA, and modulation of miR-145 may represent a promising therapeutic strategy for OA.

Funder

National Natural Science Foundation of China

Key Research and Development Program of Shandong Province

Natural Science Foundation of Shandong Province

Publisher

Bentham Science Publishers Ltd.

Subject

Organic Chemistry,Computer Science Applications,Drug Discovery,General Medicine

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