LncRNA PART‐1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR‐590‐3p sponge in osteoarthritis

Lü, Chao; Li, Zheng; Hu, Shouye; Cai, Yuanzhen; Peng, Kan

doi:10.1111/jcmm.14690

Cited by 31 publications

(18 citation statements)

References 28 publications

(49 reference statements)

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“…Here we identified miR-495 could target TGFBR2, a gene with important role in chondrocyte phenotype [15]. In this research, we found that TGFBR2 expression was lower in OA patients and IL-1β-challenged chondrocytes, which was also like that in previous study [18]. Shen et al suggested that TGFBR2 deletion could promote OA-like injury in mice [16].…”

Section: Discussionsupporting

confidence: 80%

“…Chen et al reported that TGFBR2 was targeted via lncRNA MEG3 to suppress extracellular matrix degradation of chondrocytes [17]. Furthermore, Lu et al TGFBR2 could suppress chondrocytes apoptosis in OA [18]. These previous reports have confirmed that TGFBR2 could attenuate chondrocytes apoptosis and extracellular matrix degradation induced via IL-1β.…”

Section: Discussionmentioning

confidence: 92%

“…Transforming growth factor-β receptor 2 (TGFBR2) is associated with the alteration of chondrocyte phenotype in OA [15]. Furthermore, increasing evidences report that TGFBR2 can inhibit OA-like phenotype in mice and IL-1β-challenged chondrocytes [16][17][18]. Bioinformatics analysis predicts both circSERPINE2 and TGFBR2 can bind with miR-495.…”

Section: Introductionmentioning

confidence: 99%

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CircSERPINE2 weakens IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis

Zhang¹,

Qiao²,

Xia³

2020

Bioscience Reports

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The dysregulated circular RNAs (circRNAs) are relevant to the development of osteoarthritis (OA). The circRNA serpin family E member 2 (circSERPINE2) is dysregulated in OA, while the role and mechanism of circSERPINE2 in OA are largely unknown. The aim of our research is to explore how and whether circSERPINE2 regulates interleukin-1β (IL-1β)-caused chondrocyte damage in OA. In present study, the chondrocytes (CHON-001 cells) were exposed to IL-1β to mimic the injury in OA. CircSERPINE2, microRNA-495 (miR-495) and transforming growth factor-β receptor 2 (TGFBR2) abundances were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell apoptosis was assessed via viability, apoptotic rate and caspase-3 activity. Extracellular matrix was investigated by levels of Sry-type high-mobility-group box 9 (SOX9), collagen type II alpha 1 (COL2A1) and Aggrecan using western blot. The interaction among circSERPINE2, miR-495 and TGFBR2 was assessed via dual-luciferase reporter analysis and RNA immunoprecipitation. The results showed that circSERPINE2 expression was reduced in OA patients and IL-1β-treated chondrocytes. CircSERPINE2 overexpression mitigated IL-1β-caused apoptosis and extracellular matrix degradation. miR-495 was targeted by circSERPINE2 and up-regulated in OA patients and IL-1β-treated chondrocytes. miR-495 up-regulation reversed overexpression of circSERPINE2-mediated inhibition of apoptosis and extracellular matrix degradation. TGFBR2 was targeted by miR-495 and lowly expressed in OA patients and IL-1β-treated chondrocytes. CircSERPINE2 could mediate TGFBR2 expression by binding with miR-495. As a conclusion, CircSERPINE2 attenuated IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis, indicating a new target for OA treatment.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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CircSERPINE2 weakens IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis

Zhang¹,

Qiao²,

Xia³

2020

Bioscience Reports

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“…In OA patients, the high expression of PART1 upregulates the expression of SOX4 through the ceRNA miR-373-3p , thus promoting the increased expression of MMP-13, ADAMTS4, and ADAMTS5, resulting in ECM degradation. 51 Interestingly, Lu et al 52 studied chondrocytes in OA patients and found that the expression of PART1 in OA decreased. Silencing PART1 in primary chondrocytes induced by interleukin (IL)-1β can reduce cell viability and induce apoptosis.…”

Section: Introductionmentioning

confidence: 99%

The function of lncRNAs in the pathogenesis of osteoarthritis

Jiang

Chen

et al. 2021

Bone & Joint Research

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Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2021;10(2):122–133.

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“…So far, a number of lncRNAs have been reported to possess promising prognostic or diagnostic value for OS (15,16); however, the role of prostate androgen-regulated transcript 1 (PART 1) in this malignancy is largely unknown. Recently, studies by showed that PART1 regulated the apoptosis of chondrocytes in osteoarthritis (17). A recent study by investigated the functions of PART1 in hepatocellular carcinoma and found that PART1 served as oncogenic lncRNA through sponging miR-590-3p to upregulate HMGB2 expression in hepatocellular carcinoma (18).…”

Section: Introductionmentioning

confidence: 99%

LncRNA prostate androgen-regulated transcript 1 (PART 1) functions as an oncogene in osteosarcoma via sponging miR-20b-5p to upregulate BAMBI

Pan

Liu

et al. 2021

Ann Transl Med

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Background: Osteosarcoma (OS) is an aggressive bone cancer that most commonly affects adolescents and children. Emerging studies have shown that long noncoding RNA (lncRNA) performs essential roles in the occurrence and development of many tumors. Prostate androgen-regulated transcript 1 (PART 1) has been reported as a tumor oncogene; despite this, the mechanisms underlying its involvement in OS are unclear.Methods: OS and paired normal tissue samples were obtained, and gene expressions were detected by real time-quantitative polymerase chain reaction (RT-qPCR). The functions of PART 1 in OS cell proliferation, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8) and Transwell assays. Furthermore, the binding sites of PART 1 and miR-20b-5p as well as those between miR-20b-5p and bone morphogenic protein and activin membrane-bound inhibitor homolog (BAMBI) were verified by bioinformatics analysis and dual-luciferase reporter assay.Results: Our study found obvious overexpression of PART 1 in OS tissues and cells. Furthermore, PART 1 overexpression facilitated OS cell proliferation, invasion, and migration. Further mechanistic investigations revealed that PART 1 could sponge to miR-20b-5p, which was expressed at a low level in OS tissues and cells. Importantly, miR-20b-5p overexpression inhibited OS cell proliferation, invasion, and migration.Additionally, BAMBI was confirmed as a downstream gene of miR-20b-5p, and its expression was reversely modulated by miR-20b-5p and positively modulated by PART 1. Rescue experiments suggested that BAMBI was involved in PART 1-mediated promotion of OS progression.Conclusions: PART 1 serves as a competing endogenous RNA to promote OS tumorigenesis via its regulation of the miR-20b-5p/BAMBI axis, which may provide a promising therapeutic biomarkers for OS patients.

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LncRNA PART‐1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR‐590‐3p sponge in osteoarthritis

Cited by 31 publications

References 28 publications

CircSERPINE2 weakens IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis

CircSERPINE2 weakens IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis

The function of lncRNAs in the pathogenesis of osteoarthritis

LncRNA prostate androgen-regulated transcript 1 (PART 1) functions as an oncogene in osteosarcoma via sponging miR-20b-5p to upregulate BAMBI

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