Y-J Zhu1, D-M Jiang. 1. Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Friendship Road, Yuanjiagang, Chongqing, China.fuhuyueoruzc@163.com.
Abstract
OBJECTIVE: Osteoarthritis (OA) is a common disease in articular cartilages. It has been reported that long non-coding RNAs (lncRNAs) play an important role in various pathological processes of OA. However, the role of PART1 in OA development is unclear. PATIENTS AND METHODS: The expression levels of PART1 and miR-373-3p were detected in cartilage tissues and chondrocytes using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was determined by flow cytometry and Western blot assay. The expression of extracellular matrix (ECM)-related proteins was examined by Western blot assay. Expression of SRY-related high-mobility group box 4 (SOX4) was measured by qRT-PCR or Western blot assay. The interactions among PART1, miR-373-3p, and SOX4 were predicted using starBase v2.0 database and confirmed by Dual-Luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: PART1 and SOX4 were up-regulated while miR-373-3p was down-regulated in OA cartilage tissues and chondrocytes. PART1 silencing hindered cell proliferation and ECM degradation, and triggered cell apoptosis in OA chondrocytes. PART1 modulated SOX4 expression by targeting miR-373-3p. Inhibition of miR-373-3p restored the regulation of cell proliferation, ECM degradation, and apoptosis induced by interfering PART1. Upregulation of SOX4 restored the effects on OA progression induced by inhibiting PART1. CONCLUSIONS: PART1 promoted OA progression by regulating miR-373-3p/SOX4 axis, providing an effective therapeutic target for osteoarthritis.
OBJECTIVE:Osteoarthritis (OA) is a common disease in articular cartilages. It has been reported that long non-coding RNAs (lncRNAs) play an important role in various pathological processes of OA. However, the role of PART1 in OA development is unclear. PATIENTS AND METHODS: The expression levels of PART1 and miR-373-3p were detected in cartilage tissues and chondrocytes using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was determined by flow cytometry and Western blot assay. The expression of extracellular matrix (ECM)-related proteins was examined by Western blot assay. Expression of SRY-related high-mobility group box 4 (SOX4) was measured by qRT-PCR or Western blot assay. The interactions among PART1, miR-373-3p, and SOX4 were predicted using starBase v2.0 database and confirmed by Dual-Luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: PART1 and SOX4 were up-regulated while miR-373-3p was down-regulated in OA cartilage tissues and chondrocytes. PART1 silencing hindered cell proliferation and ECM degradation, and triggered cell apoptosis in OA chondrocytes. PART1 modulated SOX4 expression by targeting miR-373-3p. Inhibition of miR-373-3p restored the regulation of cell proliferation, ECM degradation, and apoptosis induced by interfering PART1. Upregulation of SOX4 restored the effects on OA progression induced by inhibiting PART1. CONCLUSIONS: PART1 promoted OA progression by regulating miR-373-3p/SOX4 axis, providing an effective therapeutic target for osteoarthritis.
Authors: Brianne M Cruickshank; Marie-Claire D Wasson; Justin M Brown; Wasundara Fernando; Jaganathan Venkatesh; Olivia L Walker; Fiorella Morales-Quintanilla; Margaret L Dahn; Dejan Vidovic; Cheryl A Dean; Carter VanIderstine; Graham Dellaire; Paola Marcato Journal: Cancers (Basel) Date: 2021-05-27 Impact factor: 6.639