Osteopontin‐induced lncRNA HOTAIR expression is involved in osteoarthritis by regulating cell proliferation

Abstract Background Osteopontin plays critical roles in osteoarthritis (OA) by regulating the functions of osteoclasts. It is known that osteopontin can induce the expression of lncRNA HOX transcript antisense RNA (HOTAIR), indicating the involvement of HOTAIR in OA. This study was carried out to investigate the role of HOTAIR in OA. Methods Synovial fluid was extracted from both OA patients (n = 58) and healthy controls (n = 58). Expression of osteopontin and HOTAIR in synovial fluid was determined by RT-qPCR. Osteopontin was used to treat chondrocytes at dosages of 0, 1, 5 and 10 µg/ml, followed by measurement of HOTAIR expression by RT-qPCR. The role of osteopontin and HOTAIR overexpression, as well as HOTAIR knockdown in regulating the proliferation of chondrocytes was analyzed by cck-8 assay. Results HOTAIR was upregulated in OA. A positive correlation between HOTAIR and osteopontin was observed. In the primary chondrocytes, osteopontin treatment increased HOTAIR expression, while HOTAIR overexpression and knockdown failed to significantly affect osteopontin expression. In addition, osteopontin and HOTAIR overexpression increased chondrocyte proliferation, while HOTAIRE knockdown decreased chondrocyte proliferation. In addition, HOTAIR knockdown reduced the effects of osteopontin treatment on cell proliferation. Conclusions Osteopontin-induced HOTAIR expression is involved in osteoarthritis by regulating cell proliferation.

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miR-216a-5p Suppresses the Proliferation, Invasion and Migration of Fibroblast-Like Synoviocyte in Rheumatoid Arthritis by Targeting Zinc Finger and BTB Domain-Containing Protein 2 (ZBTB2)

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2589 ◽

2021 ◽

Vol 11 (5) ◽

pp. 896-902

Author(s):

Jinwei Zhao ◽

Ling Li

Keyword(s):

Rheumatoid Arthritis ◽

Cell Proliferation ◽

Zinc Finger ◽

Cell Counting ◽

Luciferase Reporter ◽

Healthy Controls ◽

Invasion And Migration ◽

Btb Domain ◽

And Migration

MicroRNAs have been reported to be associated with the initiation and progression of rheumatoid arthritis (RA). miR-216a-5p, one of the miRNAs, is involved in cancer cell proliferation, invasion and migration. However, the role of miR-216a-5p in RA remains to be explored. The expressions of miR-216a-5p and zinc finger and BTB domain-containing protein 2 (ZBTB2) in fibroblast-like synoviocytes (FLS) of RA or healthy controls were detected by qRT-PCR and western blot analysis. Transfection of overexpressed and silenced miR-216a-5p were performed to explore the functional role of miR-216a-5p in RA-FLS. Cell Counting Kit-8 (CCK-8) assay and transwell assay were employed to assess cell proliferation and cell invasion, respectively. Moreover, luciferase reporter assay was executed to verify the combination of miR-216a-5p and ZBTB2. The results showed that miR-216a-5p expression in RA-FLS was downregulated than healthy controls. Overexpres-sion of miR-216a-5p inhibited RA-FLS cell proliferation, invasion and migration, while miR-216a-5p silencing revealed the opposite results. In addition, ZBTB2 was identified to be a direct target of miR-216a-5p in RA-FLS and its expression was higher than that in healthy controls. Rescue experiments revealed that ZBTB2 overexpression reversed the effects of miR-216a-5p on the proliferation, invasion and migration of RA-FLS. These data indicated the suppressive role of miR-216a-5p in RA-FLS via the regulation of ZBTB2, suggesting that miR-216a-5p and ZBTB2 may be the new targets for the treatment of RA.

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LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000489110 ◽

2018 ◽

Vol 46 (3) ◽

pp. 1275-1285 ◽

Cited By ~ 59

Author(s):

Zhigang Xiao ◽

Zhan Qu ◽

Zhikang Chen ◽

Zhixue Fang ◽

Ke Zhou ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cell Lines ◽

Antisense Rna ◽

Vital Role ◽

Loss Of Function ◽

Human Colorectal Cancer ◽

Expression Levels ◽

Lncrna Hotair

Background/Aims: HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). Methods: We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells. The possible mechanisms of HOTAIR were also explored by fluorescence reporter assay and Western blot. Results: The expressions of HOTAIR were upregulated in CRC tissue tissues compared to adjacent control tissues. We also found HOTAIR was downregulated by miR-203a-3p in CRC cell lines. Both HOTAIR knockdown and miR-203a-3p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and GRG5 were inhibitory targets of miR-203a-3p, and that Wnt/β-catenin signaling was inhibited by both HOTAIR knockdown and miR-203a-3p overexpression. Significantly, we found that increased expression of miR-203a-3p is essential for cell proliferation repression, chemoresistance reduction, and Wnt/β-catenin signaling inhibition induced by HOTAIR knockdown. Conclusions: Our study demonstrated that the lncRNA HOTAIR could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-203a-3p and the activity of Wnt/β-catenin signaling pathway.

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On the role of galectin-3 and interleukin-6 in immune responses of rosacea patients

Immunopathology Allergology Infectology ◽

10.14427/jipai.2016.4.60 ◽

2016 ◽

pp. 60-64

Author(s):

M. Aripova ◽

A. Zima ◽

O. Vasil’eva ◽

S. Hardikova

Keyword(s):

Immune Response ◽

Immune Responses ◽

Blood Serum ◽

Interleukin 6 ◽

Clinical Manifestations ◽

Healthy Controls ◽

Positive Correlation ◽

Healthy Donors ◽

Galectin 3

Aim. Determining the level of galectin-3, IL-6 in the blood serum of patients with rosacea and rosacea in combination with chronic opisthorchiasis. Subjects and methods. In the blood serum of 80 rosacea patients, 64 patients with rosacea, combined with chronic opisthorchiasis and 20 healthy donors were studied concentrations of galectin 3, IL-6 by ELISA. Results. The concentration of galectin 3, IL-6 was significantly elevated in patients with rosacea, rosacea, combined with chronic opisthorchiasis as compared with the healthy controls. The positive correlation between the severity of clinical manifestations of rosacea and the level of galectin 3 (r = 0,72), IL-6 (r = 0,64) in the two groups. Conclusion. The results indicate an imbalance content (galectin-3; IL-6) in serum of patients with rosacea, which can be seen as further evidence of the inferiority of the immune response in rosacea.

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Circular RNA circZNF652 is overexpressed in osteoarthritis and positively regulates LPS-induced apoptosis of chondrocytes by upregulating PTEN

10.21203/rs.3.rs-58776/v1 ◽

2020 ◽

Author(s):

Xuefeng Yuan ◽

Yingchi Zhang ◽

Cong Cai ◽

Chaoxu Liu ◽

Jie Xie ◽

...

Keyword(s):

Synovial Fluid ◽

Cell Apoptosis ◽

Circular Rna ◽

Healthy Controls ◽

Inhibitory Effects ◽

Pten Mrna ◽

Apoptosis Assay ◽

Sirna Silencing ◽

Induced Apoptosis

Abstract Background Circular RNA circZNF652 promotes LPS-induced inflammation, which contributes to the development of osteoarthritis (OA), indicating the potential involvement of CRNDE in OA. This study was carried to explore the involvement of circZNF652 in OA. Methods RT-qPCR was performed to analyze the expression of circZNF652 and PTEN mRNA in synovial fluid samples from 60 OA patients and 60 healthy controls. Correlations between circZNF652 and PTEN mRNA were analyzed by Pearson’s correlation coefficient. Overexpression and siRNA silencing of circZNF652 were achieved in chondrocytes, followed by performing RT-qPCR and Western blot to analyze the expression of PTEN. The role of circZNF652 and PTEN in regulating the apoptosis of chondrocytes induced by LPS was analyzed by cell apoptosis assay. Results We found that circZNF652 was overexpressed in OA and positively correlated with PTEN mRNA. In chondrocytes, circZNF652 overexpression increased the expression of PTEN, and circZNF652 siRNA silencing decreased the expression of PTEN. Moreover, circZNF652 and PTEN positively regulated the apoptosis of chondrocytes induced by LPS. PTEN overexpression reversed the inhibitory effects of circZNF652 siRNA silencing on cell apoptosis. Conclusion CircZNF652E is overexpressed in OA and positively regulates LPS-induced apoptosis of chondrocytes by upregulating PTEN.

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17β-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway

Cellular & Molecular Biology Letters ◽

10.2478/s11658-011-0023-y ◽

2011 ◽

Vol 16 (4) ◽

Cited By ~ 32

Author(s):

Jia Huang ◽

Chun Xia ◽

Xin Zheng ◽

Ting Yi ◽

Xiao Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Expression Level ◽

Akt Pathway ◽

Chondrocyte Proliferation ◽

Common Cause ◽

Akt Activation ◽

17Β Estradiol ◽

Oa Chondrocytes ◽

The Relationship

AbstractOsteoarthritis (OA) is the most common cause of musculoskeletal pain and disability. The importance of chondrocytes in the pathogenesis of OA is unequivocal. 17β-estradiol (E2) has a potential protective effect against OA. However, the mechanism of E2 in OA chondrocytes remains unclear. In this study, we investigated the regulative effect of E2 on cell growth and the relationship between E2 and the PI3K/Akt pathway in rat OA model chondrocytes (pretreated with interleukin-1β). We found that E2 induced chondrocyte proliferation, and increased the expression level of Akt simultaneously, especially the expression level of P-Akt. Furthermore, the inhibition of P-Akt could block chondrocyte proliferation induced by E2. These results suggest that PI3K/Akt activation induced by E2 may be an important factor in the mechanism of E2 in cell proliferation in rat OA model chondrocytes, and help further understanding the role of E2 in OA progression.

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AB0111 THE COMPARISON OF SYNDECAN-4 LEVEL IN SERA, SYNOVIAL FLUID AND SYNOVIUM OF RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1587 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1356.1-1356

Author(s):

J. Zhao ◽

X. Ye ◽

Z. Zhang

Keyword(s):

Rheumatoid Arthritis ◽

Cell Migration ◽

Synovial Fluid ◽

Disease Activity ◽

Immune Cell ◽

Inflammatory Responses ◽

Heparan Sulphate ◽

Healthy Controls ◽

Baseline Serum

Background:Syndecan-4, one of the members of heparan sulphate proteoglycans (HSPGs), has been shown to be involved in regulating inflammatory responses, angiogenesis, and cell migration. Its role has been proved in animal arthritis models, however not clearly elucidated in rheumatoid arthritis (RA) patientsObjectives:To investigate the role of Syndecan-4 in the pathogenesis of RA, by detecting Syndecan-4 expression in the serum, synovial fluid and synovium of RA patients and comparing with osteoarthritis (OA) patientsMethods:The concentrations of syndecan-4 in sera and synovial fluid of RA and osteoarthritis (OA) patients were detected by ELISA. The expression of syndecan-4 in synovium of RA and OA patients was detected by immunohistochemistry. In another cohort of 60 RA patients, the association analysis was performed. All the RA patients were with disease duration more than 6 months and with DAS28-CRP>3.2 although after csDMARDs (including MTX and/or leflunomide) treatment for more than 3 months. The RA patients were treated with tumour necrosis factor α (TNFα) inhibitor (TNFi) and MTX 10mg per week for 12 weeks. The correlations between sera Syndecan-4 and disease activity of RA as well as therapeutic response to TNFi were analyzed.Results:The serum Syndedcan-4 level of RA patients [637.1 (483.6-1069.6) pg/mL] was significantly higher than that of OA patients [345.0 (287.9-421.1) pg/mL] and healthy controls [195.6 (165.0-225.2) pg/mL](P<0.001, P<0.001, respectively). The serum concentration of Syndecan-4 is also higher in OA patients than that in healthy controls (P<0.001). It was also higher in RF-positive RA patients than in RF-negative ones [603.0 (100.0-8879.1) pg/mL vs 460.3 (178.7-2468.9) pg/mL, (p=0.026)]. The Syndedcan-4 level in synovial fluid and synovia were comparable between RA and OA patients. No correlation was found between serum Syndedcan-4 and disease activity of RA. TNFi treatment did not change the serum Syndecan-4 level significantly. The baseline serum Syndecan-4 did not show predictive value for TNFi response.Conclusion:Syndecan-4 can be expressed in the synovia of RA and OA patients. The serum Syndecan-4 is higher in RA patients than in OA patients and healthy controls, and significantly higher in sero-positive RA patients than in sero-negative ones. Syndecan-4 may participate in the pathogenesis of RA.References:[1]Leonova EI, Galzitskaya OV. Role of Syndecans in Lipid Metabolism and Human Diseases. Adv Exp Med Biol, 2015, 855: 241-58.[2]Xie J, Wang J, Li R, Dai Q, Yong Y, Zong B, et al. Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction. J Mol Cell Cardiol 2012; 53: 250-8.[3]Strand ME, Aronsen JM, Braathen B, Sjaastad I, Kvaløy H, Tønnessen T, et al. Shedding of syndecan-4 promotes immune cell recruitment and mitigates cardiac dysfunction after lipopolysaccharide challenge in mice. J Mol Cell Cardiol. 2015;88:133-44.[4]Endo T, Ito K, Morimoto J, Kanayama M, Ota D, Ikesue M, et al. Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation. Arthritis Rheumatol. 2015; 67:2512-22.Disclosure of Interests:None declared

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CDKN2B antisense RNA 1 suppresses tumor growth in human colorectal cancer by targeting MAPK inactivator dual-specificity phosphatase 1

Carcinogenesis ◽

10.1093/carcin/bgab077 ◽

2021 ◽

Author(s):

Jie Pan ◽

Mengxin Lin ◽

Zongbin Xu ◽

Meifang Xu ◽

Junrong Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Protein Kinase ◽

Antisense Rna ◽

Mitogen Activated Protein Kinase ◽

Human Colorectal Cancer ◽

Dual Specificity ◽

Mitogen Activated Protein

Abstract Aberrant expression of long noncoding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) has been detected in human colorectal cancer (CRC). This study aimed to investigate the role of CDKN2B-AS1 and the underlying mechanism in human CRC. Gain- and loss-of-function assays were performed to explore the role of CDKN2B-AS1 in the malignant behavior of HCT116 and SW480 CRC cells in vitro and in vivo. RNA pull-down assay was conducted to identify the target of CDKN2B-AS1 in CRC cells. The physical and functional interactions between CDKN2B-AS1 and the target were examined. CDKN2B-AS1 inhibited CRC cell proliferation and migration while promoting apoptosis in vitro via activation of mitogen-activated protein kinase kinases (MEK)/extracellular signal-regulated kinase (ERK)/p38 signaling. CDKN2B-AS1 bound to mitogen-activated protein kinase (MAPK) inactivator dual-specificity phosphatase 1 (DUSP1) in CRC cells. In contrast to CDKN2B-AS1, DUSP1 promoted CRC cell proliferation, suppressed apoptosis and inactivated MEK/ERK/p38 signaling in CRC cells. Furthermore, CDKN2B-AS1 overexpression attenuated DUSP1 expression in normal colonic myofibroblasts and CRC cells. Overexpression of DUSP1 effectively countered the activation of MEK/ERK/p38 signaling induced by CDKN2B-AS1 overexpression or further blocked MEK/ERK/p38 signaling suppressed by CDKN2B-AS1 silencing. In the mouse xenograft model, CDKN2B-AS1 suppressed CRC growth, whereas DUSP1 promoted CRC growth. CDKN2B-AS1 induced cell apoptosis while suppressing EMT (epithelial–mesenchymal transition), whereas DUSP1 suppressed cell apoptosis while inducing EMT in CRC, as evidenced by the alterations in the protein levels of apoptosis and EMT markers in tumor tissue samples. CDKN2B-AS1 regulates CRC cell growth and survival by targeting MAPK inactivator DUSP1.

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Decreased levels of serum platelet-activating factor acetylhydrolase in patients with rheumatic diseases

Mediators of Inflammation ◽

10.1080/09629359791758 ◽

1997 ◽

Vol 6 (3) ◽

pp. 241-242 ◽

Cited By ~ 4

Author(s):

P. Vergne ◽

V. Praloran ◽

R. Treves ◽

Y. Denizot

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Rheumatic Diseases ◽

Potential Role ◽

Platelet Activating Factor ◽

Healthy Controls ◽

Elevated Blood ◽

Platelet Activating Factor Acetylhydrolase ◽

Paf Acetylhydrolase

PAF is a potent inflammatory compound known to stimulate the release of various cytokines involved in rheumatic diseases. Elevated blood PAF levels are reported in these patients. We report that serum PAF acetylhydrolase activity (AHA) levels are decreased in patients with rheumatoid arthritis or osteoarthritis as compared to healthy controls. Serum and synovial fluid AHA levels were correlated in these patients. The present study suggests the potential role of AHA in controling systemic and/or local PAF levels in patients with rheumatic diseases.

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