syedzayyan/paper_mill_benchmark huggingface dataset:
DDP-resistant ovarian cancer cells-derived exosomal microRNA-30a-5p reduces the resistance of ovarian cancer cells to DDP

Exosomes carrying micro rnas (mi rnas) have been demonstrated to play critical roles in the regulation of development, growth and metastasis of cancer.Bioinformatic predictions identified differentially expressed sry-box 9 (sox9) in oc, and the regulatory mi rna mi r-139-5p.Here, we aim to evaluate the function of exosomal mi r-139-5p in the sensitivity of ovarian cancer (oc) cells to cis-diamminedichloroplatinum(ii) (ddp).Expression pattern of mi r-139-5p and sox9 in ovarian cancer cells (skov3) and ddp-resistant cells (skov3/ddp) was identified using reverse transcription quantitative polymerase chain reaction and western blot analysis.The relationship between mi r-139-5p and sox9 was validated using a dual-luciferase reporter assay.Skov3/ddp cell line was developed and introduced with mi r-30a-5p mimic to analyse the effects of mi r-30a-5p on resistance to ddp.The in vitro and in vivo effects of exosomal mi r-30a-5p on resistance of skov3 cells to ddp were assessed in a co-culture system of exosomes and oc cells as well as in tumour-bearing nude mice.High expression of sox9 and low expression of mi r-30-5p were witnessed in oc.Furthermore, mi r-30-5p, a downregulated mi rna in skov3/ddp cells, increased the rate of cell apoptosis and enhanced the sensitivity of skov3/ddp cells to ddp by targeting sox9.Moreover, exosomes carrying mi r-30a-5p were identified to sensitize skov3/ddp cells to ddp both in vitro and in vivo .These data together supported an important conclusion that ddp-resistant oc cell-derived exosomal mi r-30a-5p enhanced cellular sensitivity to ddp, highlighting a potential strategy to overcome drug resistance.

Journal: Open Biology (2020)
Publication types: Research Article;
Micro-RNA-143 inhibits proliferation and promotes apoptosis of thymocytes by targeting CXCL13 in a myasthenia gravis mouse model

Myasthenia gravis (mg) is an autoimmune neuromuscular disorder, affecting the quality of life of millions of people worldwide.The present study aims to determine the relationship between micro-rna-143 (mi r-143) and c-x-c motif chemokine 13 (cxcl13) and whether it influences the pathogenesis of myasthenia gravis (mg).Thymus specimens were resected from patients with thymic hyperplasia combined with mg and then infused into normal mouse cavities to establish mg mouse models.Immunohistochemistry, reverse transcription-quantitative pcr, in situ hybridization detection, and western blot analysis were employed to identify the expression of mi r-143 and cxcl13 in mg and normal mice.The obtained thymocytes were cultured in vitro and transfected with a series of mi r-143 mimic, mi r-143 inhibitor, overexpression of cxcl13, or si rna against cxcl13.Mtt [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and flow cytometry assays were employed to assess cell viability, cycle entry, and apoptosis of the thymocytes.Dual-luciferase reporter assay provided verification, confirming that cxcl13 was the target gene of mi r-143.Low mi r-143 expression in the thymus tissues of the mg mice was detected, which presented with a reciprocal relationship with the expression rate of clcx13.Observations in relation to the interactions between mi r-143 mimic or si rna-cxcl13 exposure showed reduced cell viability, with a greater number of cells arrested at the g0/g1 phase and a greater rate of induced apoptosis.Furthermore, overexpression of cxcl13 rescued mi r-143 mimic-induced apoptosis.The findings have identified the potential role of mi r-143 as a mg development mediator by targeting cxcl13.The key results obtained provide a promising experimental basis for targeted intervention treatment with mi r-143.

Journal: American Journal of Physiology - Cell Physiology (2019)
Publication types: Research Article;
Knockdown of Long Non-Coding RNA RP11-445H22.4 Alleviates LPS-Induced Injuries by Regulation of MiR-301a in Osteoarthritis

Several long non-coding rnas (lnc rnas) play vital roles in osteoarthritis (oa), whereas the role of lnc rna rp11-445h22.4 in oa remains unclear.The study aimed to investigate the effect of lnc rna rp11-445h22.4 on lipopolysaccharide (lps)-induced cell viability, apoptosis and inflammatory injury of oa.Methods: the expression of rp11-445h22.4, mi r-301a and cxcr4 in human cartilage atdc5 cells were altered by transfection, and then cells were exposed to 5 μg/ml lps for 12 h.Then cell viability, apoptosis, apoptosis-related factors and inflammatory cytokines were analyzed by cck-8, flow cytometry, western blot, rt-q pcr and elisa, respectively.Dual-luciferase reporter assay was performed to assess the binging sites of rp11-445h22.4 and mi r-301a.The signal pathways of nf-κb and mapk/ erk were determined by western blot.Results: lps reduced cell viability, increased apoptosis and stimulated release of il-1β, il-6, il-8 and tnf-α.However, rp11-445h22.4 inhibition significantly rescued lps-induced injuries by promoting cell viability, suppressing apoptosis and inflammatory cytokines secretions in atdc5 cells.In addition, mi r-301a directly bound to rp11-445h22.4, and suppression of mi r-301a inversed the effects of rp11-445h22.4 inhibition.Furthermore, cxcr4 was a direct target of mi r-301a, and cxcr4 silencing increased cell viability, decreased apoptosis and inflammatory cytokines secretions in lps-treated atdc5 cells.Besides, we found that cxcr4 silencing blocked lps-activated nf-κb and mapk/erk pathways.Conclusions: the study indicated that lnc rna rp11-445h22.4-mi r-301a-cxcr4 axis played an important role in cartilage atdc5 cells and provided a theoretical basis of lnc rna rp11-445h22.4 in oa.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124

Hulc is a multifunctional lnc rna that has pro-angiogenic function in various cancers.The present study was designed to see the role of lnc rna hulc in normal endothelial cells angiogenesis.Methods: cell viability, apoptosis, migration, tube formation and expression levels of angiogenesis-related proteins were respectively assessed in human microvascular endothelial hmec-1 cells after lnc rna hulc was silenced by sh rna transfection.Cross-regulation between lnc rna hulc and mi r-124, and between mi r-124 and mcl-1 were detected by q rt-pcr, sequence analysis, and luciferase reporter assay.Results: silence of lnc rna hulc significantly reduced viability, migration, tube formation and protein levels of vegf, vegfr2, cd144 and e nos in hmec-1 cells.Meanwhile, silence of lnc rna hulc induced apoptosis in hmec-1 cells, as bcl-2 was down-regulated, bax was up-regulated, and caspase-3 and -9 were cleaved.Mi r-124 expression was negatively regulated by lnc rna hulc, and hulc worked as a molecular sponge for mi r-124, in having mi r-124 exhausted.Besides, mcl-1 was a target gene of mi r-124.Rescue assay results showed that the effects of lnc rna hulc silence on hmec-1 cells growth, migration and angiogenesis were abolished by mi r-124 suppression.Similarly, the effects of mi r-124 on hmec-1 cells were abolished by mcl-1 overexpression.Furthermore, mcl-1 activated pi3k/akt and jak/stat signaling pathways.Conclusion: these findings suggest a pro-angiogenic role of lnc rna hulc in endothelial cells.The pro-angiogenic actions of lnc rna hulc may be through sponging mi r-124, preventing mcl-1 from degradation by mi r-124.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
Astragaloside IV Protects Rat Cardiomyocytes from Hypoxia-Induced Injury by Down- Regulation of miR-23a and miR-92a

Astragaloside iv (as-iv), a traditional chinese medicine isolated from astragalus membranaceus, has been shown to exert cardioprotective effect previously.This study aimed to reveal the effects of as-iv on hypoxia-injured cardiomyocyte.Methods: h9c2 cells were treated with various doses of as-iv for 24 h upon hypoxia.Cck-8 assay, flow cytometry/western blot, and q rt-pcr were respectively conducted to measure the changes in cell viability, apoptosis, and the expression of mi r-23a and mi r-92a.Sprague–dawley rats were received coronary ligation, and were administrated by various doses of as-iv for 14 days.The infarct volume and outcome of rats followed by ligation were tested by ultrasound, arteriopuncture and nitrotetrazolium blue chloride (nbt) staining.Results: we found that 10 μg/ml of as-iv exerted myocardioprotective effects against hypoxia-induced cell damage, as as-iv significantly increased h9c2 cells viability and decreased apoptosis.Interestingly, the myocardioprotective effects of as-iv were alleviated by mi r-23a and/or mi r-92a overexpression.Knockdown of mi r-23a and mi r-92a activated pi3k/akt and mapk/ erk signaling pathways.Bcl-2 was a target gene for mi r-23a, and bcl2l2 was a target gene for mi r-92a.In the animal model of myocardial infarction (mi), as-iv significantly reduced the infarct volume, ejection fraction (ef), shortening fraction (fs) and lv systolic pressure (lvsp), and significantly increased left ventricular end-diastolic internal diameter (lvedd).And also, the elevated expression of mi r-23a and mi r-92a in mi rat was reduced by as-iv.Conclusion: as-iv protected cardiomyocytes against hypoxia-induced injury possibly via down-regulation of mi r-23a and mi r-92a, and via activation of pi3k/akt and mapk/erk signaling pathways.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
Propofol Inhibits Proliferation, Migration, Invasion and Promotes Apoptosis Through Down-Regulating miR-374a in Hepatocarcinoma Cell Lines

Propofol is a commonly used anaesthetic with controversial effects on cancer cells.We aimed to explore the functional roles of propofol in hepatocellular carcinoma (hcc) cells as well as the underlying mechanisms.Methods: hep g2 and smmc-7721 cells were used in this study.Firstly, the effects of propofol on cell viability, migration, invasion, apoptosis, and involved proteins were assessed by cell counting kit-8 assay, transwell assay, flow cytometry assay and western blot analysis, respectively.Subsequently, alteration of mi r-374a after stimulation of propofol was analyzed by q rt-pcr.Mi r-374a was overexpressed and the alteration of proteins in the wnt/β-catenin and pi3k/akt pathways was detected by western blot analysis.The downstream factor of mi r-374a was finally studied.Results: propofol inhibited cell viability, migration and invasion but promoted apoptosis of hep g2 and smmc-7721 cells.Meanwhile, cyclin d1, matrix metalloproteinase (mmp)-2 and mmp-9 were down-regulated while bax/bcl-2, cleaved caspase-3 and cleaved caspase-9 were up-regulated by propofol.Then, mi r-374a level was reduced by propofol.Expression of wnt3a, β-catenin, p-pi3k and p-akt was decreased by propofol, whereas these decreases were reversed by mi r-374a overexpression.Finally, tp53 was proven to be target of mi r-374a in hep g2 cells.Conclusion: propofol inhibited cell proliferation, migration and invasion while promoted cell apoptosis of hep g2 and smmc-7721 cells through inhibiting the wnt/β-catenin and pi3k/ akt pathways via down-regulation of mi r-374a.Besides, mi r-374a affected propofol-treated hep g2 cells by targeting tp53.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
Zurampic Protects Pancreatic β-Cells from High Uric Acid Induced-Damage by Inhibiting URAT1 and Inactivating the ROS/AMPK/ERK Pathways

Zurampic is a us fda approved drug for treatment of gout.However, the influence of zurampic on pancreatic β-cells remains unclear.The study aimed to evaluate the effects of zurampic on high uric acid-induced damage of pancreatic β-cells and the possible underlying mechanisms.Methods: ins-1 cells and primary rat islets were stimulated with zurampic and the m rna expression of urate transporter 1 (urat1) was assessed by q rt-pcr.Cells were stimulated with uric acid or uric acid plus zurampic, and cell viability, apoptosis and ros release were measured by mtt and flow cytometry assays.Western blot analysis was performed to evaluate the expressions of active caspase-3 and phosphorylation of ampk and erk.Finally, cells were stimulated with uric acid or uric acid plus zurampic at low/high level of glucose (2.8/16.7 m m glucose), and the insulin release was assessed by elisa.Results: m rna expression of urat1 was decreased by zurampic in a dose-dependent manner.Uric acid decreased cell viability, promoted cell apoptosis and induced ros release.Uric acid-induced alterations could be reversed by zurampic.Activation of caspase-3 and phosphorylation of ampk and erk were enhanced by uric acid, and the enhancements were reversed by zurampic.Decreased phosphorylation of ampk and erk, induced by zurampic, was further reduced by adding inhibitor of ampk or erk.Besides, uric acid inhibited high glucose-induced insulin secretion and the inhibition was rescued by zurampic.Conclusions: zurampic has a protective effect on pancreatic β-cells against uric acid induced-damage by inhibiting urat1 and inactivating the ros/ampk/erk pathway.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
Acetylation of GATA4 on Lysine Residue K313 Promotes Osteoblastic Cells Growth

Gata4, a protein related to osteoblast differentiation and mineralization, whose acetylation is essential for cardiac defects.Here, we aimed to explore the functional impacts of gata4 acetylation on osteoporosis (os).Methods: gata4 acetylation in h fob1.19 and 293t cells was detected after exposure of hdac inhibitors (tsa and saha).Co-immunoprecipitation was conducted to determine which hats and hdacs was involved in the modulation of gata4 acetylation/deacetylation, and to identify the acetylation site.The transcriptional activity of gata4 was measured in the presence or absence of cycloheximide.Furthermore, h fob1.19 cells viability and apoptosis were evaluated after transfection with acetylation-defective mutant of gata4.Results: as a result, gata4 acetylation was identified as a pivotal event in h fob1.19 cells.Gata4 can be acetylated by p300/cbp, and the acetylation site was on lysine residue k313.Besides, the acetylation of gata4 can be impaired by hdac1, rather than by hdac2-5.Gata4 acetylation contributed to the stability and transcription of gata4.Moreover, gata4 acetylation activated ccnd2 transcription, and mutation of gata4 on k-313 reduced cell viability and increased a mitochondria-dependent apoptosis in h fob1.19 cells.Conclusion: our data suggest that gata4 exists as an acetylated protein in h fob1.19 cells.Acetylation regulates the stability and transcription of gata4, and activates ccnd2 transcription, which may explain the growth-promoting functions of gata4 in h fob1.19 cells.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
LncRNA GAS5 Represses Osteosarcoma Cells Growth and Metastasis via Sponging MiR-203a

Lnc rna gas5, a growth suppressor, has been reported to exert anti-tumor actions in various cancers, whereas the exact mechanism underling the anti-tumor action is still unclear.This study was aimed to investigate the effect of lnc rna gas5 on osteosarcoma and tried to decode the underling mechanisms.Methods: expressions of lnc rna gas5 in mg-63 cells were silenced by sh rna transfection, while were overexpressed by vector transfection.Cell viability, migration, invasion and apoptosis were respectively assessed by mtt, transwell assay and flow cytometry.Regulations between lnc rna gas5 and mi r-203a, as well as between mi r-203a and timp2 were detected by q pcr, western blot and dual luciferase activity assay.Results: lnc rna gas5 was down-regulated in mg-63 and os-732 cells compared to h fob1.19 cells.Silence of lnc rna gas5 significantly promoted mg-63 cells viability, migration and invasion, and up-regulated cyclin d1, cyclin b1, cdk1 and cdk4 expressions.Mi r-203a was negatively regulated by lnc rna gas5.The promoting activities of lnc rna gas5 silence on mg-63 cells growth and metastasis were reversed by mi r-203a suppression.Timp2 was a target of mi r-203a and the anti-growth and anti-metastasis actions of mi r-203a suppression were reversed by timp2 silence.Further, lnc rna gas5 silence, mi r-203a overexpression, and timp2 silence could activate pi3k/akt/gsk3β signaling while block nf-κb signaling.Conclusion: lnc rna gas5 might be a tumor suppressor in osteosarcoma via sponging mi r-203a, sequestering mi r-203a away from timp2.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the Articular Chondrocytes

Osteoarthritis (oa) as a degenerative disease is a major problem in ageing populations.To better understand the molecular mechanisms in the pathogenesis of oa, this study explored the role of micro rna (mi r)-146a in the articular chondrocytes.Methods: the articular chondrocyte line atdc5 was used to simulate inflammatory injury by lps administration in vitro.Cell viability, apoptosis, m rna expressions and productions of inflammatory factors were assessed, respectively.Mir-146a and cxcr4 m rna expressions were measured by q rt-pcr.Targeting effect of mi r-146a on cxcr4 3’utr was assessed by luciferase activity analysis.Protein expression levels of cxcr4 and main factors in pi3k/akt, wnt/β-catenin signal pathways were measured by western blotting.Results: lps exposure suppressed cell viability, prompted apoptosis of atdc5 cells, and stimulated expression and release of inflammatory factors.Mi r-146a was upregulated in lps-induced cells.Overexpression of mi r-146a further aggravated lps-induced inflammatory injury, while it was reduced after mi r-146a was knocked down.Cxcr4 expression was negatively regulated by mi r-146a.Cxcr4 was a direct target of mi r-146a and thus involved in regulatory effect of mi r-146a on the injured chondrocytes, which was also related with phosphorylation levels of pi3k/akt and expressions of wnt/β-catenin signal factors.Conclusion: mi r-146a promoted inflammatory response of articular chondrocytes via targeting cxcr4 and suppressing cxcr4 expression.Overexpression of cxcr4 could attenuate the inflammatory injury.Our findings provided novel evidence which might be useful for further studies exploring therapeutic approaches for oa via targeting mi r-146a.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139

Acute myocardial infarction (ami) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia.The present study evaluated the effects of long non-coding rna h19 on hypoxic rat h9c2 cells and mouse hl-1 cells.Methods: hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using mtt, transwell and flow cytometry assays, respectively.H19 expression after hypoxia was estimated by q rt-pcr.We then measured the effects of non-physiologically expressed h19, knockdown of mi r-139 with or without h19 silence, and abnormally expressed sox8 on hypoxia-induced h9c2 cells.Moreover, the interacted mi rna for h19 and downstream target gene were virtually screened and verified.The involved signaling pathways and the effects of abnormally expressed h19 on contractility of hl-1 cells were explored via western blot analysis.Results: hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of h19.Knockdown of h19 increased hypoxia-induced injury in h9c2 cells.H19 acted as a sponge for mi r-139 and h19 knockdown aggravated hypoxia-induced injury by up-regulating mi r-139.Sox8 was identified as a target of mi r-139, and its expression was negatively regulated by mi r-139.The mechanistic studies revealed that overexpression of sox8 might decrease hypoxia-induced cell injury by activating the pi3k/akt/m tor pathway and mapk.Besides, h19 promoted contractility of hl-1 cells.Conclusion: these findings suggest that h19 alleviates hypoxia-induced myocardial cell injury by mi r-139-mediated up-regulation of sox8, along with activation of the pi3k/akt/m tor pathway and mapk.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1

This study aimed to investigate the potential roles of mi r-424 expression in non-small cell lung cancer (nsclc) metastasis and growth and its underlying mechanism.Methods: the expression of mi r-424 in two nsclc cell lines (a549 and h1975) was altered by transfection with mi r-424 mimic and inhibitor.Effects of mi r-424 overexpression and suppression on cells migration, invasion and colony formation were analyzed.Target genes for mi r-424 were predicted using bioinformatics method and then verified using luciferase assay.Effects of mi r-424 expression on cell migration, invasion and proliferation were reanalyzed on the condition of tnfaip1 was silenced.Moreover, tnfaip1 silencing and mi r-424 modified a549 cells were subcutaneous injected into node balb/c mice to confirm the regulation of mi r-424 on tnfaip1 in regulating tumor growth.Results: compared with the control, mi r-424 overexpression significantly increased the migrated and invaded cells, as well as the proliferated colonies.Tnfaip1 was a predicted target gene for mi r-424, and was negatively regulated by mi r-424.Tnfaip1 silence significantly increased the migrated and invaded cells compared to that in control, while these increases were abolished by mi r-424 suppression.Animal experiment further evidenced mi r-424 affected tumor growth by regulating tnfaip1.Conclusions: these data demonstrate that mi r-424 may be a contributor for nsclc progression and metastasis through involving in cell migration, invasion and proliferation via inhibiting tnfaip1.This study may provide theoretical basis for mi r-424 in nsclc target therapeutic treatment.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;