scholarly journals Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1) Promotes Viability of Rheumatoid Arthritis Fibroblast-Like Synoviocytes

2021 ◽  
Author(s):  
Yong Chen ◽  
Baojiang Wang ◽  
Yanjuan Chen ◽  
Qunyan Wu ◽  
Kutty Selva Nandakumar ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Inhibitory Effect ◽  
Migration Ability ◽  
Ki 67 ◽  
Link Protein ◽  
Over Expression ◽  
Proliferation Capacity ◽  
And Migration ◽  
Fibroblast Like Synoviocytes ◽  
Proliferation And Migration

Abstract Background To investigate HAPLN1 contribution to the viability of RA-FLSs and identify its potential role in RA pathogenesis. Methods Plasma levels and synovial expression of HAPLN1 were compared between healthy controls, and osteoarthritis (OA) and RA patients. Proliferation and migration of RA-FLSs transfected with siHAPLN1, HAPLN1OE (over-expression vector) and respective controls or treated with rHAPLN1 were measured by MTT and CCK8 assays as well as wound healing and transwell assays. RT-qPCR and automated WB analysis were used to compare the expression of AMPK-ɑ, TNF-ɑ, TGF-β, ACAN, MMPs, Cyclin-D1 and Ki-67 after siHAPLN1 or HAPLN1OE transfection. Proteomics and mRNA-seq analysis was done to study the differentially expressed proteins/genes after siHAPLN1 or rHAPLN1 treatment. Results Expression of HAPLN1 was increased in the plasma samples and synovium tissues of RA patients. HAPLN1OE transfected or rHAPLN1 treated RA-FLSs showed an increased proliferation capacity. However, Si-HAPLN1 has failed to affect the viability of RA-FLSs, though it decreased the migration ability of these cells. On the other hand, HAPLN1OE or rHAPLN1 had inhibitory effect on migration. Both si-HAPLN1 and HAPLN1OE treated RA-FLSs had down-regulated AMPK-ɑ gene expression, while protein level was found to be up-regulated. Furthermore, si-HAPLN1 has down-regulated TNF-ɑ, MMPs, IL-6, TGF-β, fibronectin and ACAN levels, while HAPLN1OE has up-regulated the levels of TNF-ɑ, MMPs, IL-6 and ACAN. Proteomics and mRNA-Seq analysis demonstrated HAPLN1 function in the activation of inflammation, proliferation, increased cell adhesion and strengthening of ECM function. Conclusons: HAPLN1 accelerated the proliferation of RA-FLSs but inhibited its migration ability. HAPLN1 network was found to be mainly involved in the activation of inflammation, cell proliferation and increased cell adhesion.

scholarly journals Mesenchymal Stem Cells Inhibit the Proliferation and Migration of Fibroblast-like Synoviocytes in Rheumatoid Arthritis via Exosome-mediated Delivery of miRNAs

2021 ◽  
Author(s):  
Liangyu Mi ◽  
Na Li ◽  
Jinfang Gao ◽  
Xinyue Peng ◽  
Na Zhang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Real Time ◽  
Joint Inflammation ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
Surface Markers ◽  
Tissue Destruction ◽  
And Migration ◽  
Fibroblast Like Synoviocytes ◽  
Proliferation And Migration

Abstract BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by aggressive and symmetrical polyarthritis. Fibroblast-Like Synoviocytes(FLSs)play a central role in the pathogenesis of RA. The abnormal expression of miRNAs in RA FLSs mediates RA joint inflammation，synovial hyperplasia，and tissue destruction; MSC-Exos-derived miRNAs are a potential RA treatment strategy. This study aimed to investigate the hUCMSC-Exos can deliver miRNA to RA FLSs and affect their biological properties. MethodsPrimary hUCMSCs were isolated and cultured by tissue adherence method，and surface markers were identified by flow cytometry. We used differential centrifugation combined with ultrafiltration to obtain hUCMSC-Exos and identify them；The primary RA FLSs were isolated and cultured by trypsin digestion，then surface markers were identified by flow cytometry. We labeled the RNA of hUCMSC-Exos. hUCMSC-Exos was co-cultured with RA FLSs then the dyed RA FLSs were observed with a fluorescence microscope. GV493 with siRNA target sequences that could knock down Ago2 transfected hUCMSCs. Real-time PCR and Westen blot analysis Ago2 levels in hUCMSCs and transfected hUCMSCs to determine knockdown efficiency. Lentivirus GV493 with the target with the highest knockdown efficiency to transfect hUCMSCs，named hUCMSCKD3-Ago2. Then hUCMSC-Exos，hUCMSCKD3-Ago2 -Exos，hUCMSC NC-Exos were extracted by the differential centrifugal method combined ultrafiltration method，then were identified. The real-time cell analysis was used to detected the proliferation and migration of RA FLSs in different concentrations of hUCMSC-Exos. Finally，we used the optimal concentration of hUCMSCKD3-Ago2 -Exos and hUCMSC NC-Exos to intervene in RA FLSs. ResultsAfter incubation with hUCMSC-Exos and RA FLSs，the hUCMSC-Exos accumulated in the blue nuclei of RA FLSs. hUCMSCNC-Exos and hUCMSCKD-Ago2-Exos inhibited the proliferation and migration of RA FLSs compared ，particularly the hUCMSCNC-Exos had the significant inhibitory effect. ConclusionshUCMSC-Exos RNA can be taken up by RA FLSs，and hUCMSC may affect the proliferation and migration of RA FLSs via exosome-mediated delivery of miRNA.

SOX4 Serves an Oncogenic Role in the Tumourigenesis of Human Breast Adenocarcinoma by Promoting Cell Proliferation, Migration and Inhibiting Apoptosis

2020 ◽  
Vol 15 (1) ◽  
pp. 49-58
Author(s):  
Junhe Zhang ◽  
Shujie Chai ◽  
Xinyu Ruan
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Caspase 3 ◽  
Breast Adenocarcinoma ◽  
Migration Ability ◽  
Expression Levels ◽  
Apoptosis Rate ◽  
And Migration ◽  
Mcf 7 ◽  
Proliferation And Migration

Background: Breast cancer is among the most common malignant cancers worldwide, and breast adenocarcinoma in glandular tissue cells has excessive metastasis and invasion capability. However, little is known on the molecular process by which this disease develops and progresses. Objective: In this study, we explored the effects of sex-determining region Y-box 4 (SOX4) protein on proliferation, migration, apoptosis and tumourigenesis of breast adenocarcinoma and its possible mechanisms. Methods: The SOX4 overexpression or knockdown Michigan Cancer Foundation-7 (MCF-7) cell lines were established. Among the SOX4 overexpression or MCF-7 knockdown cell lines, proliferation, migration ability and apoptosis rate were detected. The expression levels of apoptosis-related proteins (Bax and Cleaved caspase-3) were analysed using Western blot. The effect of SOX4 on tumourigenesis was analysed using the clone formation assay in vitro and tumour xenograft experiment in nude mice. Results: Compared with the overexpression of control cells, proliferation and migration ability of SOX4 overexpression cells significantly increased, the apoptosis rate significantly decreased in addition to the expression levels of Bax and Cleaved caspase-3 (P < 0.05). Compared with the knockdown of control cells, proliferation and migration ability of SOX4 knockdown cells significantly decreased, and the apoptosis rate and expression levels of Bax and Cleaved caspase-3 significantly increased (P < 0.05). Clone formation and tumour growth abilities of SOX4 overexpression cells were significantly higher than those of the control cells (P < 0.05), whereas SOX4 knockdown cells had the opposite effect. Conclusion: SOX4 plays an oncogenic role in breast adenocarcinoma tumourigenesis by promoting cell proliferation, migration and inhibiting apoptosis. It can be used as a potential molecular target for breast cancer gene therapy.

scholarly journals Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

2021 ◽  
Vol 22 (11) ◽  
pp. 5602
Author(s):  
Hyeon Young Park ◽  
Mi-Jin Kim ◽  
Seunghyeong Lee ◽  
Jonghwa Jin ◽  
Sungwoo Lee ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Inhibitory Effect ◽  
Metabolic Reprogramming ◽  
Neointima Formation ◽  
Artery Ligation ◽  
Carotid Artery Ligation ◽  
And Migration ◽  
Proliferation And Migration

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis and restenosis. Glycolysis and glutaminolysis are increased in rapidly proliferating VSMCs to support their increased energy requirements and biomass production. Thus, it is essential to develop new pharmacological tools that regulate metabolic reprogramming in VSMCs for treatment of atherosclerosis. The effects of 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist, have been broadly investigated in highly proliferative cells; however, it is unclear whether DON inhibits proliferation of VSMCs and neointima formation. Here, we investigated the effects of DON on neointima formation in vivo as well as proliferation and migration of VSMCs in vitro. DON simultaneously inhibited FBS- or PDGF-stimulated glycolysis and glutaminolysis as well as mammalian target of rapamycin complex I activity in growth factor-stimulated VSMCs, and thereby suppressed their proliferation and migration. Furthermore, a DON-derived prodrug, named JHU-083, significantly attenuated carotid artery ligation-induced neointima formation in mice. Our results suggest that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis.

scholarly journals Expression of AIM2 in rheumatoid arthritis and its role on fibroblast-like synoviocyte

2020 ◽  
Author(s):  
fujuan qiu ◽  
Chen Yong ◽  
Qiu Fujuan ◽  
Zhao Xiaofeng ◽  
Xiao Changhong
Keyword(s):  
Rheumatoid Arthritis ◽  
Mtt Assay ◽  
Control Group ◽  
Expression Levels ◽  
Potential Target ◽  
Caspase 1 ◽  
Significant Difference ◽  
And Migration ◽  
Fibroblast Like Synoviocytes ◽  
Proliferation And Migration

Abstract Background To determine whether any differences of AIM2 inflammasome expression levels between rheumatoid arthritis (RA) and osteoarthritis (OA) and investigate the effects of AIM2 when transferred into RA fibroblast-like synoviocytes (RA-FLS).Methods Serum AIM2 levels between OA and RA patients were compared by ELISA. Different expression levels of AIM2, ASC, Caspase-1 and IL-1β between RA and OA synovium were semi-quantified by RT-qPCR and immunohistochemical (IHC) staining. IHC staining were recorded by H scores, and determine the correlation with ESR and CRP levels of RA patients. SiRNA AIM2 was transferred to RA-FLS and observe its effects on proliferation and migration by MTT assay and transwell test respectively.Results In RA sera, no significant difference was observed between OA and RA patients. However, in affected knee synovium, AIM2, ASC, Caspase-1 and IL-1β were expressed higher in RA than that of OA. Plus, H score of AIM2, ASC, and IL-1β were positively correlated to ESR and CRP levels in RA patients. After transferred AIM2 siRNA to FLS and incubation for 48 hours, the proliferation of FLS were significantly inhibited, and the apoptosis rate were significantly increased compared to FLS in control group. However, no effect on migration was detected.Conclusions AIM2 participated in the proliferation of FLS, and might be a potential target for therapy.

scholarly journals Over-expression of ANP32E is associated with poor prognosis of pancreatic cancer and promotes cell proliferation and migration through regulating β-catenin

2020 ◽  
Author(s):  
Jianwei Zhang ◽  
Zhongmin Lan ◽  
Guotong Qiu ◽  
Hu Ren ◽  
Yajie Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Cell Cycle Progression ◽  
Over Expression ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract Background: Pancreatic cancer is a malignant tumor with high mortality. Acidic nuclear phosphoprotein 32 family member E (ANP32E), a specific H2A.Z chaperone, has been shown to contribute to breast cancer development. However, the significance of ANP32E in pancreatic cancer is poorly understood. This study aimed to investigate the role of ANP32E in pancreatic cancer. Methods: The expression of ANP32E in 179 pancreatic cancer tissues and 171 normal tissues, and the correlation between ANP32E expression and patients’ survival were analyzed from the TCGA database. ANP32E was over-expressed and silenced using lentivirus. siRNA was used to knock down β-catenin. CCK8, colony formation, cell cycle and transwell experiments were performed to determine cell proliferation and migration. qRT-PCR and Western blot were conducted to detect mRNA and protein expression. Results: ANP32E was up-regulated in pancreatic cancer tissues and cells. Up-regulation of ANP32E predicted poor prognosis in pancreatic cancer patients. Lentivirus-mediated knockdown of ANP32E suppressed the proliferation, colony growth and migration of PANC1 and MIA cells. By contrast, ANP32E over-expression promoted the proliferation and migration of both cells. In addition, ANP32E accelerated the cell cycle progression in PANC1 and MIA cells. Molecular experiments showed that ANP32E activated β-catenin/cyclin D1 signaling. Silencing of β-catenin reduced cell proliferation and migration in ANP32E over-expressed cells. Conclusion: Our results propose that ANP32E functions as an oncogene in pancreatic cancer via activating β-catenin.

scholarly journals MicroRNA-145 Involves in the Pathogenesis of Renal Vascular Lesions and May Become a Potential Therapeutic Target in Patients with Juvenile Lupus Nephritis

2019 ◽  
Vol 44 (4) ◽  
pp. 643-655 ◽  
Author(s):  
Zhaomin Cai ◽  
Wei Xiang ◽  
Xiaojie Peng ◽  
Yan Ding ◽  
Wang Liao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Lupus Nephritis ◽  
Smooth Muscle Actin ◽  
Vascular Lesions ◽  
Alpha Smooth Muscle Actin ◽  
Migration Ability ◽  
Phenotypic Transformation ◽  
And Migration ◽  
Renal Vascular ◽  
Proliferation And Migration

Aims: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism. Methods: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN). Results: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased. Conclusions: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.

scholarly journals LMNA functions as an oncogene in hepatocellular carcinoma by regulating the proliferation and migration ability

2020 ◽  
Vol 24 (20) ◽  
pp. 12008-12019
Author(s):  
Heng Liu ◽  
Dongming Li ◽  
Ling Zhou ◽  
Shuang Kan ◽  
Guozhang He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Migration Ability ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals MiR-1-3p Suppresses the Proliferation, Invasion and Migration of Bladder Cancer Cells by Up-Regulating SFRP1 Expression

2017 ◽  
Vol 41 (3) ◽  
pp. 1179-1188 ◽  
Author(s):  
Anquan Shang ◽  
Man Yang ◽  
Fujun Shen ◽  
Jun Wang ◽  
Jun Wei ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Migration Ability ◽  
Invasion And Migration ◽  
Over Expression ◽  
Normal Tissues ◽  
Sfrp1 Expression ◽  
Bladder Cancer Cells ◽  
And Migration ◽  
Cancer Tissues

Background: Bladder cancer is of compelling morbidity and mortality due to its high recurrence rate. Little development has been made in the last decades in the therapy methods. Thus, the mechanism of its growth and invasiveness involving novel molecular targets are needed. Objective: Our research objective is to confirm the hypothesis that miR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells. Methods: The expression levels of miR-1-3p and SFRP1 were evaluated using RT-qPCR in bladder cancer tissues and cells as well as in normal tissues and cells. J82 cell lines were selected as experiment subjects due to their low expression levels of miR-1-3p. Plasmids carrying miR-1-3p mimics, miR-1-3p inhibitors and SFRP1 were transfected into the J82 cell lines. Subsequently, the protein expression of SFRP1 was detected using Western Blot analysis, and cell proliferation, apoptosis, invasion and migration ability was measured using MTT, the flow cytometry, the Transwell test and wound healing assays, respectively Results: Bladder cancer tissues and cells exhibited significant decrease in the expression of miR-1-3p and SFRP1 compared to normal tissues and cells, and human bladder cancer cell line J82 exhibited the most significant decrease in these expressions (P < 0.05). MiR-1-3p up-regulates SFRP1 expression in bladder cancer cells, and the over-expression of miR-1-3p can suppress the proliferation, invasion and migration ability of bladder cancer cells. This mechanism is similar to the effect of SFRP1 over-expression on bladder cancer cells. Conclusion: MiR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells by up-regulating SFRP1 expression.

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