Over-expression of microRNA-145 Elevating Autophagy Activities via Downregulating FRS2 Expression
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Published:2024-01
Issue:1
Volume:27
Page:127-135
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ISSN:1386-2073
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Container-title:Combinatorial Chemistry & High Throughput Screening
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language:en
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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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