syedzayyan/paper_mill_benchmark huggingface dataset:
Long noncoding RNA ASBEL promotes osteosarcoma cell proliferation, migration, and invasion by regulating microRNA‐21

Osteosarcoma is the most common malignant bone tumor in children and adolescents with high rate of incidence, high frequency of recurrence, and high degree of metastasis.This study aimed to investigate the effects of long noncoding rna antisense nc rna in the abundant in neuroepithelium area (ana)/b‐cell translocation gene 3 (btg3) locus (lnc rna asbel) on the pathogenesis of osteosarcoma.The expression levels of asbel in human osteoblast cells and human osteosarcoma cells were evaluated using q rt‐pcr.Effects of asbel knockdown on cell viability, migration, and invasion were detected using trypan blue exclusion assay, cell migration, and cell invasion assay, respectively.The regulatory effects of asbel on micro rna‐21 (mi r‐21) were analyzed using q rt‐pcr.The roles of mi r‐21 and protein phosphatase 2a (pp2a), the possible downstream factor of mi r‐21, in osteosarcoma cell proliferation, migration, and invasion were also explored.The results showed that asbel was highly expressed in osteosarcoma cells.Knockdown of asbel inhibited osteosarcoma cell viability, migration, and invasion, as well as the expression level of mi r‐21.Pp2a was a direct target of mi r‐21, which participated in the effects of asbel and mi r‐21 on the activation of phosphatidylinositol 3‐kinase/protein kinase 3/glycogen synthase kinase‐3β (pi3k/akt/gsk3β) and mitogen‐activated protein kinase/extracellular regulated protein kinase (mek/erk) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion.In conclusion, we verified that asbel‐mi r‐21‐pp2a pathway might play critical regulatory effects on the pathogenesis of osteosarcoma and could be as the potential therapeutic target and biomarker for osteosarcoma treatment.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
LncRNA H19 promotes epithelial‐mesenchymal transition (EMT) by targeting miR‐484 in human lung cancer cells’

Recently, the long non‐coding rna (lnc rna) h19 has been identified as an oncogenic gene in multiple cancer types.However, the molecular basis for this observation has not been characterized in lung cancer, especially during epithelial mesenchymal transition (emt) progression.Cell viability, migration, invasion, and apoptosis were measured using trypan blue exclusion assay, transwell migration/invasion assay, and flow cytometry, respectively.Quantitative rt‐pcr was used to measure relative expressions of h19, micro r‐484 (mi r‐484), and rho associated coiled‐coil containing protein kinase 2 (rock2).Western blot was used to measure expressions of apoptosis‐, emt‐, and c‐jun n‐terminal kinase (jnk) pathway‐related proteins.Luciferase reporter assay was used to identify the target of h19.H19 was highly expressed in both lung cancer tissues and cells.Suppression of h19 significantly decreased a549 cell viability, migration, and invasion, but promoted apoptosis.Overexpression of h19 promoted cell migration, invasion, and emt process.Mi r‐484 was a target of h19 and overexpression of it reversed the effects of h19 on emt.Mi r‐484 regulated the expression of rock2.Mechanistic study revealed that suppressing h19 decreased the expression of proteins in jnk pathway, and rock2 was the main downstream molecule of h19.H19 promoted emt in lung cancer a549 cells by negatively regulating mi r‐484.

Journal: Journal of Cellular Biochemistry (2017)
Publication types: Research Article;
Knockdown of lncRNA HULC inhibits proliferation, migration, invasion, and promotes apoptosis by sponging miR‐122 in osteosarcoma

Osteosarcoma is a rare malignant bone tumor with high degree of malignancy.Hulc (highly upregulated in liver cancer), a long noncoding rna (lnc rna) was involved in hepatocellular carcinoma development and progression, but its underlying mechanism in osteosarcoma is unknown.The aim of this study was to explore the functional role of hulc in osteosarcoma.The study was conducted in human osteosarcoma cell lines and the expression of hulc in the cell lines was detected by q rt‐pcr.Furthermore, the effects of hulc on tumorigenicity of osteosarcoma cells were evaluated by in vitro assays.Results revealed that hulc was highly expressed in osteosarcoma mg63 and os‐732 cells compared to osteoblast h fob1.19 cells.Suppression of hulc in osteosarcoma cells inhibited cell viability, migration, invasion, and promoted apoptosis.Hulc functioned as an endogenous sponge for mi r‐122, and its silence functioned through upregulating mi r‐122.Hnf4g was a target of mi r‐122, and the effect of hnf4g on os‐732 cells was the same as hulc.Furthermore, overexpression of mi r‐122 inactivated pi3k/akt, jak/stat, and notch pathways by downregulation of hnf4g.These findings suggest that knockdown of hulc inhibited proliferation, migration, and invasion by sponging mi r‐122 in osteosarcoma cells.Hulc may act as a novel therapeutic target for management of osteosarcoma.

Journal: Journal of Cellular Biochemistry (2017)
Publication types: Research Article;
MicroRNA-150-5p affects cell proliferation, apoptosis, and EMT by regulation of the BRAF V600E mutation in papillary thyroid cancer cells

Papillary thyroid cancer (ptc) is the most common endocrine malignancy.Studies have confirmed an association between micro rna (mi rna) and the braf v600e mutation in various cellular biological processes of ptc.This study aimed to clarify the potential relationship between mi r‐150‐5p and the braf v600e mutation in ptc.Human ptc cell lines b‐cpap and tpc‐1 were transfected with the mi r‐150‐5p mimic, an inhibitor, and the corresponding controls.Then, cell proliferation, viability, and apoptosis were detected by bromodeoxyuridine, trypan blue exclusion, and flow cytometry assays.The expressions of the main factors of cell cycle, epithelial mesenchymal transition (emt), and dna mismatch repair were examined by western blot analysis and a real‐time quantitative polymerase chain reaction.Additionally, pc‐braf v600e was transfected into b‐cpap and tpc‐1 cells to determine the relationship between mi r‐150‐5p and braf v600e .In addition, the methyl ethyl ketone (mek)/extracellular signal‐regulated kinase (erk) signal pathway was examined using western blot analysis.Overexpression of mi r‐150‐5p promoted cell proliferation and viability, inhibited apoptosis, and upregulated cell cycle factor expressions at 50 passages of b‐cpap and tpc‐1 cells after transfection.Overexpression of mi r‐150‐5p led to an obvious decrease in e‐cadherin expression, but enhanced n‐cadherin, slug and vimentin, zeb1, and snail expression.Moreover, overexpression of mi r‐150‐5p markedly suppressed pold3, msh2, and msh3 expression.Furthermore, braf v600e overexpression increased the expression level of mi r‐150‐5p in tpc cells, and overexpression of telomerase reverse transcriptase further enhanced the promoting effect of braf v600e on mi r‐150‐5p expression in b‐cpap and tpc‐1 cells.Finally, braf v600e overexpression activated the mek/erk signal pathway in b‐cpap and tpc‐1 cells.These data indicated that mi r‐150‐5p promoted cell proliferation, suppressed apoptosis, and accelerated the emt process by regulation of the braf v600e mutation.Our findings will help elucidate the pathogenesis of ptc and identify biomarkers.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Baicalin prevents tumor necrosis factor‐α−induced apoptosis and dysfunction of pancreatic β‐cell line Min6 via upregulation of miR‐205

Baicalin (bai), one major flavonoid from scutellaria baicalensis , possesses anticancer and anti‐inflammatory properties.However, the effect of bai on diabetes mellitus has not been investigated.This study explored the antidiabetic effect of bai on pancreatic β‐cell line min6.Min6 cells were treated with tumor necrosis factor‐α (tnf‐α) to mimic β‐cell destruction in type 1 diabetes mellitus.The effects of bai on viability and apoptosis of min6 cells were analyzed by the cell counting kit‐8 assay and annexin v‐fluoresceine isothiocyanate/propidium iodide staining method.The insulin secretion of min6 cells was determined using radioimmunoassay.Expression of apoptosis‐associated proteins and inducible nitric oxide synthase (i nos), and activation of phosphatidylinositol 3ʹ‐kinase/protein kinase b (pi3k/akt) and nuclear factor κb (nf‐κb) pathways were analyzed by western blot analysis.Relative micro rna‐205 (mi r‐205) expression was determined by quantitative real time polymerase chain reaction.Tnf‐α treatment inhibited cell growth and insulin secretion, but promoted i nos expression.All of these effects were reversed by bai treatment.Bai promoted viability; suppressed apoptosis; regulated caspase‐3, b‐cell lymphoma 2 and bcl‐2‐associated x protein; decreased i nos level; and increased insulin production.Bai protected min6 cells by upregulating mi r‐205.Besides, the min6 cell‐protective effect of bai was pi3k/akt pathway and nf‐κb pathway dependent.Bai activated the pi3k/akt pathway and inhibited the nf‐κb pathway by regulating mi r‐205.In conclusion, bai protected min6 cells from tnf‐α‐induced injury by upregulating mi r‐205, which acts, at least in part, via activation of the pi3k/akt pathway and inactivation of the nf‐κb pathway.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
MircoRNA-1275 promotes proliferation, invasion and migration of glioma cells via SERPINE1

This study was designed to explore the relationship between mi r‐1275 and serpine1 and its effects on glioma cell proliferation, migration, invasion and apoptosis.Differentially expressed mi rnas and m rnas in glioma tissues were screened out by bioinformatic analysis.Dual‐luciferase reporter gene assay was used to validate the targeted relationship between mi r‐1275 and serpine1.Q rt‐pcr was used to detect the expression of mi r‐1275 and serpine1 in glioma tissues.The expressions of serpine1 and p53 pathway‐related proteins in glioma cells were detected by western blot.Glioma cell proliferation, apoptosis, migration and invasion were respectively detected by cck‐8 assay, flow cytometry, wound healing assay and transwell assay.Tumour xenograft model was developed to study the influence of mi r‐1275 and serpine1 on glioma growth in vivo.The results of microarray analysis, q rt‐pcr and western blot showed that mi r‐1275 was low‐expressed while serpine1 was high‐expressed in glioma.Dual‐luciferase assay showed that mi r‐1275 could bind to serpine1.Overexpression of mi r‐1275 could promote the p53 pathway‐related proteins’ expression.Highly expressed mi r‐1275 could repress the migration, proliferation and invasion of glioma cells while highly expressed serpine1 had inverse effects.Tumour xenograft showed that up‐regulated mi r‐1275 or down‐regulated serpine1 could repress glioma growth in vivo.Up‐regulation of mi r‐1275 activated p53 signalling pathway via regulating serpine1 and therefore suppressed glioma cell proliferation, invasion and migration, whereas promoted cell apoptosis.

Journal: Journal of Cellular and Molecular Medicine (JCMM) (2018)
Publication types: Research Article;
Tetramethylpyrazine partially relieves hypoxia-caused damage of cardiomyocytes H9c2 by downregulation of miR-449a

Inadequate oxygen supply is probably one of the most important pathophysiological mechanisms of cardiomyocyte damage in ischemic heart disease.Tetramethylpyrazine (tmp, also known as ligustrazine) is the main active ingredient isolated from the rhizome of ligusticum chuanxiong hort.A previous study reported that the tmp could exert cardioprotective activity.This study aimed to explore the molecular mechanism of the protective effects of tmp on cardiomyocyte damage caused by hypoxia.The viability and apoptosis of cardiomyocytes h9c2 were detected using cell counting kit‐8 assay and annexin v‐fitc/pi staining, respectively.Quantitative reverse transcription polymerase chain reaction was conducted to measure the expression level of micro rna‐449a (mi r‐449a).Cell transfection was performed to upregulate the expression level of mi r‐449a or downregulate the expression level of sirtuin 1 (sirt1).The protein expression levels of sirt1 and key factors involved in cell apoptosis and phosphatidylinositol 3‐kinase/protein kinase 3 (pi3k/akt) pathway were evaluated using western blot analysis.We found that the hypoxia incubation inhibited h9c2 viability, induced cell apoptosis, and inactivated the pi3k/akt pathway.Tmp treatment partially relieved the hypoxia‐caused h9c2 cell viability loss and apoptosis, as well as reversed the hypoxia‐caused inactivation of the pi3k/akt pathway.Moreover, tmp partially alleviated the upregulation of mi r‐449a in h9c2 cells caused by hypoxia.Overexpression of mi r‐449a weakened the effects of tmp on hypoxia‐treated h9c2 cells.Furthermore, sirt1 was a target gene of mi r‐449a.Knockdown of sirt1 also weakened the effects of tmp on hypoxia‐treated h9c2 cells.In conclusion, tmp partially relieved hypoxia‐caused cardiomyocytes h9c2 viability loss and apoptosis at least through downregulating mi r‐499a, upregulating sirt1, and then activating the pi3k/akt pathway.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Ras–ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac

Ras–extracellular signal‐regulated protein kinases 1 and 2 (erk1/2) signaling has been proposed as the crucial regulators in the development of various cancers.Histone acetylation at h3 lysine 14 (h3k14ac) is closely associated with gene expression and dna damage.However, whether h3k14ac participates in mediating ras–erk1/2‐induced cell proliferation and migration in uveal melanoma cells remains unknown.The purpose of this study is to investigate the effect of h3k14ac on ras–erk1/2 affected uveal melanoma cell phenotypes.Mp65 cells were transfected with ras wt and ras g12v/t35s , the unloaded plasmid of p egfp‐n1 served as a negative control.Protein levels of phosphorylated erk1/2 thr202 and h3k14ac were assessed by western blot assay.Cell viability, number of colonies, migration, and the downstream genes of erk1/2 were analyzed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2‐h‐tetrazolium bromide, soft‐agar colony formation, transwell, and chromatin immunoprecipitation assays.Ha‐tag vectors of clr3 and tip60 and the small interfering rnas that specific for clr3 and mdm2 were transfected into mp65 cells to uncover the effects of clr3, tip60, and mdm2 on ras–erk1/2 mediated h3k14ac expression and mp65 cell phenotypes.We found that, ras–erk1/2 decreased h3k14ac expression in mp65 cells, and h3k14ac significantly suppressed ras–erk1/2‐induced cell viability, colony formation, and migration in mp65 cells.Moreover, the transcription of cyr61 , igfbp3 , wnt16b , nt5e , gdf15 , and card16 was regulated by h3k14ac.Additionally, clr3 silence recovered h3k14ac expression and reversed the effect of ras–erk1/2 on mp65 cell proliferation, migration and the m rnas of erk1/2 downstream genes.Besides, ras–erk1/2 decreased h3k14ac expression by mdm2‐mediated tip60 degradation.In conclusion, ras–erk1/2 promoted uveal melanoma cells growth and migration by downregulating h3k14ac via mdm2‐mediated tip60 degradation.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Long noncoding RNA CHRF exacerbates IL-6-induced inflammatory damages by downregulating microRNA-146a in ATDC5 cells

Osteoarthritis (oa) is a frequent chronic musculoskeletal disorder which lacks applicably effective therapeutic strategy.In this study, we attempted to investigate whether long noncoding rna (lnc rna) cardiac hypertrophy‐related factor (chrf) participated in mediating interleukin‐6 (il‐6)‐induced in vitro inflammatory damages as well as the regulatory mechanisms.Atdc5 cells were stimulated with il‐6, and then cellular damages were evaluated on the basis of cell viability by cck‐8, apoptotic cells by observation with flow cytometry, apoptosis‐associated proteins by western blot analysis, and accumulation of inflammatory factors by quantitative reverse transcription polymerase chain reaction (rt‐q pcr), enzyme‐linked immunosorbent assay (elisa), and western blot analysis.Then, effects of lnc rna chrf on il‐6‐treated cells were evaluated.We further explored the downstream factor of lnc rna chrf and demonstrated whether lnc rna chrf functioned through the downstream factor.Afterwards, crucial signaling cascades were anatomized.We found that il‐6 reduced cell viability, elevated apoptosis, induced upregulation of inflammatory factors, as well as upregulated lnc rna chrf and down‐regulated mi r‐146a expression.Then, we found lnc rna chrf overexpression aggravated il‐6‐induced alterations, and lnc rna chrf knockdown showed the opposite effects.Furthermore, mi r‐146a was identified to be negatively regulated by lnc rna chrf, and its overexpression abrogated the roles of lnc rna chrf in il‐6‐treated cells.Il‐6‐induced the accumulation of iκbα, p65, jak1, and stat3 at phosphorylated level was further facilitated by lnc rna chrf whereas repressed by mi r‐146a.In conclusion, lnc rna chrf aggravated the il‐6‐induced inflammatory damages in atdc5 cells.We further outlined a possible mechanism that through downregulating mi r‐146a, lnc rna chrf evoked the activation of nf‐κb and jak1/stat3 signaling cascades.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Magnesium protects mouse hippocampal HT22 cells against hypoxia‐induced injury by upregulation of miR‐221

Magnesium (mg 2+ ) has been shown to exert neuroprotective effects against hypoxia.However, it still remains elusive whether mg 2+ protected mouse hippocampal ht22 cells against hypoxia‐evoked damages.Therefore, we aimed to investigate the function of mg 2+ and mechanisms associated with micro rna‐221 (mi r‐221).Ht22 cells were exposed to 3% o 2 for 24 hours to induce hypoxic damages with 21% as a normoxic culture condition.The damages were monitored by viability, migration, and apoptosis of ht22 cells with or without mg 2+ pretreatment.Quantitative reverse transcription‐polymerase chain reaction (q rt‐pcr) was applied to examine the alteration of mi r‐221, mi r‐210, and mi r‐17‐5p.Transduction was carried out to artificially alter the expression of mi r‐221 and nerve growth factor (ngf), which was confirmed by q rt‐pcr or western blot assays.To blunt phosphoinositide 3‐kinase (pi3k)/protein kinase b (akt) and nuclear factor κb (nf‐κb), ly294002 (10 μm) and bay 11‐7082 (10 μm) were used.We observed mg 2+ protected ht22 cells against hypoxia‐induced damages by upregulating mi r‐221.Further, mi r‐221 positively regulated ngf expression.Overexpression of ngf alleviated cell injury, while suppression of ngf aggravated cell injury.Moreover, mi r‐221 elevated ngf by inducing phosphorylation of regulators in pi3k/akt and nf‐κb transduction cascades and then alleviated cell injury.In conclusion, mg 2+ protected ht22 cells against hypoxia‐induced damages by upregulation of mi r‐221 and ngf.These findings provided insights into the development of improved strategies for clinical application.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;
MicroRNA‐136 promotes lipopolysaccharide‐induced ATDC5 cell injury and inflammatory cytokine expression by targeting myeloid cell leukemia 1

Osteoarthritis is the most frequent chronic bone and joint diseases in older populations all over the world.Lipopolysaccharide (lps)‐induced murine chondrogenic atdc5 cell model has been widely used for testing new osteoarthritis therapeutic targets.This study aimed to explore the effects of micro rna‐136 (mi r‐136) on lps‐induced atdc5 cell injury and inflammatory cytokine expression, as well as underlying potential mechanism.We found that lps remarkably inhibited atdc5 cell viability, induced atdc5 cell apoptosis, and upregulated the expression of inflammatory cytokines, including interleukin 1β (il‐1β), il‐6, il‐8, and tumor necrosis factor α (tnf‐α; p &lt; .01 or &lt; .001).Moreover, lps obviously upregulated the expression of mi r‐136 in atdc5 cells ( p &lt; .05).Overexpression of mi r‐136 markedly exacerbated the lps‐induced atdc5 cell viability inhibition, cell apoptosis enhancement, and inflammatory cytokine expression ( p &lt; .05), and suppression of mi r‐136 had opposite effects ( p &lt; .05).Myeloid cell leukemia 1 (mcl‐1) was a direct target gene of mi r‐136, which participated in the effect of mi r‐136 on lps‐induced atdc5 cell inflammatory injury.Overexpression of mcl‐1 alleviated the lps‐induced inactivation of wnt/β‐catenin and janus kinase/signal transducer and activator of transcription (jak/stat) signaling pathways, while suppression of mcl‐1 had opposite effects.To conclude, this study verified that mi r‐136 promoted lps‐induced atdc5 cell injury and inflammatory cytokine expression by targeting mcl‐1, and mcl‐1 was involved in the regulatory effects of lps on wnt/β‐catenin and jak/stat signaling pathways in atdc5 cells.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
MicroRNA‐126 Inhibits Proliferation, Migration, Invasion, and EMT in Osteosarcoma by Targeting ZEB1

Osteosarcoma (os) is a tumor with rapid progression, high metastatic potential and poor clinical prognosis.This study was aimed to investigate the function of mi r‐126 in os cells.The mi r‐126 expression in os cell lines and os tissues were explored by q rt‐pcr.Then, the effects of mi r‐126 on proliferation, cycle, migration, invasion, and transforming growth factor (tgf)‐β1 induced epithelial to mesenchymal transition (emt) were assessed.Predicted by target scan, one of target genes for mi r‐126 was verified by luciferase activity assay.Meantime, the m rna and protein expressions of zeb1 were assessed by q rt‐pcr and western blot assay.Subsequently, the effect of zeb1 silence on mi r‐126 down‐regulated cells was also evaluated.Finally, the expressions of key kinases involved in c‐jun n‐terminal kinase (jnk) and janus‐activated kinase (jak)‐1/signal transducer and activator of transcription (stat)‐3 pathways were detected by western blot analysis.Result showed that mi r‐126 was down‐regulated in os tissues and cell lines.Overexpression of mi r‐126 significantly inhibited cell proliferation, migration, invasion, and tgf‐β1 induced emt.The effect of mi r‐126 knockdown was just the opposite.Zeb1 was predicted and verified as a target gene of mi r‐126.Meantime, the influence of mi r‐126 knockdown was abrogated by zeb1 silence.Additionally, the phosphorylation levels of c‐jun, jnk, jak1, and stat3 were down‐regulated in mi r‐126 over‐expressed cells, and the effect of mi r‐126 knockdown was reversed by zeb1 silence.In conclusion, mi r‐126 inhibits proliferation, migration, invasion and emt in os by targeting zeb1 through inactivation of jnk and jak1/stat3 pathways.J.Cell.Biochem.118: 3765–3774, 2017.© 2017 wiley periodicals, inc.

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