syedzayyan/paper_mill_benchmark huggingface dataset:
Upregulation of microRNA-140-3p inhibits epithelial-mesenchymal transition, invasion, and metastasis of hepatocellular carcinoma through inactivation of the MAPK signaling pathway by targeting GRN

Invasion and metastasis in hepatocellular carcinoma (hcc) results in poor prognosis.Human intervention in these pathological processes may benefit the treatment of hcc.The aim of the present study is to elucidate the mechanism of mi r‐140‐3p affecting epithelial‐mesenchymal transition (emt), invasion, and metastasis in hcc.Microarray analysis was performed for differentially expressed genes screening.The target relationship between mi r‐140‐3p and grn was analyzed.Small interfering rna (si rna) against granulin (grn) was synthesized.Emt markers were detected, and invasion and migration were evaluated in hcc cells introduced with a mi r‐140‐3p inhibitor or mimic, or si rna against grn.A mechanistic investigation was conducted for the determination of mitogen‐activated protein kinase (mapk) signaling pathway‐related genes and emt markers (e‐cadherin, n‐cadherin, and vimentin).Grn was highlighted as an upregulated gene in hcc.Grn was a target gene of mi r‐140‐3p.Elevation of mi r‐140‐3p or inhibition of grn restrained the emt process and suppressed the hcc cell migration and invasion.Hcc cells treated with the mi r‐140‐3p mimic or si rna‐grn exhibited decreased grn expression and downregulated the expressions of the mapk signaling pathway‐related genes, n‐cadherin, and vimentin but upregulated the expression of e‐cadherin.Grn silencing can reverse the activation of the mapk signaling pathway and induction of emt mediated by mi r‐140‐3p inhibition.Taken together, the results show that mi r‐140‐3p confers suppression of the mapk signaling pathway by targeting grn, thus inhibiting emt, invasion, and metastasis in hcc.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;
Inhibition of microRNA-940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled-related protein 1–mediated Wnt/β-catenin signaling pathway

Osteosarcoma (os) is the most common malignant tumor of bone with a high potential for metastasis.This study intends to explore whether micro rna‐940 (mi r‐940) affects the development of os cells and the underlying mechanism.Os and adjacent normal tissues were collected from os patients; the os cell line with the highest expression of mi r‐940 was selected, which was then subjected to transfection of mi r‐940 mimic, mi r‐940 inhibitor, si rna‐secreted frizzled‐related protein 1 ( sfrp1 ) or li cl (agonists of wnt/β‐catenin pathway) to identify regulation of mi r‐940 to os cells through sfrp1 .The targeting relationship between mi r‐940 and sfrp1 was verified using dual‐luciferase reporter gene assay.Reverse‐transcription quantitative polymerase chain reaction and western blot assay were performed to determine mi r‐940, sfrp1 , β‐catenin, and cyclin d1 and apoptosis‐related genes fas, bax, and bcl‐2.Mtt (3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide) assay, scratch test, transwell assay, and flow cytometry were carried out to detect proliferation, migration, invasion, and apoptosis, respectively.Nude mice models were established to observe the tumor formation.Higher expression of mi r‐940, β‐catenin, and cyclin d1 and lower sfrp1 expression were identified in os tissues.Mi r‐940 targeted and negatively regulated sfrp1 expression.Furthermore, upregulated mi r‐940 expression activated the wnt/β‐catenin signaling pathway in os.With the treatment of mi r‐940 mimic, li cl, or si rna‐ sfrp1 , os cells showed promoted proliferation, migration, invasion, tumor formation, and impeded apoptosis (further reflected by elevated bcl‐2 expression and reduced fas and bax expression).The study demonstrates that mi r‐940 can promote the proliferation, migration, and invasion but suppress the apoptosis of human os cells by downregulating sfrp1 through activating wnt/β‐catenin signaling pathway.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
MiRNA-506 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targetting TLR4

Fibroblast-like synoviocytes (flss) play a crucial role in rheumatoid arthritis (ra) pathogenesis.While mi rna (mi r)-506 has been implicated in the progression of multiple diseases, its role in ra remains to be explored.The present study evaluated the function of mi r-506 in the regulation of ra-flss.Flss were prepared from ra and healthy synovial tissues.The expression of mi r-506 was measured by quantitative real time pcr (q rt-pcr).The effects of mi r-506 on ra-flss proliferation and apoptosis were detected by cell counting kit-8 and flow cytometry assays, respectively.The determination of tnf-α, il-6, and il-1β concentrations in ra-flss supernatant were done by elisa.The levels of mi r-506 were detected to be significantly lower in the synovial tissues and flss of ra than in the synovial tissues and flss of healthy controls.The mi r-506 up-regulation in ra-flss significantly inhibited the proliferation and promoted cell cycle arrest at the g0/g1 phase.The overexpression of mi r-506 induced apoptosis, along with an increase in activities of caspase-3 and -8.A target gene toll-like receptor 4 (tlr4) under the direct regulation of mi r-506 was identified through the luciferase assay, q rt-pcr and western blot analysis.Forced overexpression of tlr4 in the rescue experiments showed that tlr4 effectively reversed the effect on proliferation and apoptosis in mi r-506-overexpressing ra-flss.Thus, mi r-506 may be a potential target for ra prevention and therapy of ra.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
Functional analyses of microRNA-326 in breast cancer development

Micro rna-326 (mi r-326) was reported to be dysregulated and involved in the progression of multiple cancers.However, the clinical significance, biological role and underlying mechanism of mi r-326 in the carcinogenesis of breast cancer are still unclear.In the present study, we showed that mi r-326 was down-regulated in human breast cancer tissues and cell lines.Our results also revealed that mi r-326 overexpression significantly suppressed breast cancer cell proliferation, migration and invasion, and induced cell cycle arrest at g1/g0 phase.Furthermore, sex determining region y-box (sox) protein 12 (sox12), a known oncogene, was identified as a direct target of mi r-326 by luciferase reporter assay.Moreover, mi r-326 expression was inversely correlated with sox12 m rna expression levels in human breast cancer specimens.Overexpression of sox12 partially rescued the inhibitory effect on cell proliferation, migration and invasion in breast cancer cells caused by mi r-326 overexpression.These findings suggested that mi r-326 might play a suppressive role in breast cancer, at least in part, by targeting sox12, rendering mi r-326 a promising therapeutic target for breast cancer.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
Inhibitory role of lentivirus-mediated aquaporin-4 gene silencing in the formation of glial scar in a rat model of traumatic brain injury

Traumatic brain injury (tbi), an acute degenerative pathology of the central nervous system, is a leading cause of death and disability.As the glial scar is a mechanical barrier to nerve regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration.Herein, we aim to investigate the effects of aquaporin‐4 (aqp4) gene silencing on the glial scar formation after tbi by establishing rat models.After modeling, tbi rats were transfected with aqp4 small hairpin rna [sh rna] (aqp4 gene silencing by lentiviral vector–delivered sh rna) and empty vectors, respectively.Neurological functions of the rats were evaluated after tbi.The hematoxylin and eosin staining was conducted to observe histomorphological changes in rat brain tissues.The messenger rna (m rna) and protein expressions of glial fibrillary acidic protein (gfap), vimentin, fibronectin, laminin, and aqp4 were measured by reverse transcription‐quantitative polymerase chain reaction and western blot analysis.The ratio of positive expression area was calculated, and the glial scar was observed by immunohistochemistry.At the 7th, 14th, and 28th days after tbi, tbi rats treated with aqp4 sh rna showed improved neurological function and lessened histomorphological changes.Aqp4 gene silencing mediated by lentivirus decreased the m rna and protein expressions of gfap, vimentin, fibronectin, and laminin, the number of positive cells, the ratio of positive expression area, and the glial scar.Our study demonstrates that lentivirus‐mediated aqp4 gene silencing could inhibit the formation of glial scar after tbi, which is beneficial to the recovery of neurological function.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
microRNA-542-5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen-activated protein kinase signaling pathway through the negative regulation of P21-activated kinase 1

Severe acute pancreatitis (sap) is a condition associated with high rates of mortality and lengthy hospital stays.In the current study, sap mouse models were established in balb/c wild‐type and p21‐activated kinase 1 (pak1) knockdown mice with the objective of determining the expression of micro rna‐542‐5p (mi r‐542‐5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ali) by mediating mitogen‐activated protein kinase (mapk) signaling and binding to pak1.The targeting relationship between mi r‐542‐5p and pak1 was verified using the bioinformatics prediction website and by the means of a dual‐luciferase reporter assay.Following the sap model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with mi r‐542‐5p on inflammatory reactions among mice with sap‐associated ali.Our results indicated that pak1 was targeted and negatively mediated by mi r‐542‐5p.Mice with sap‐associated ali exhibited an increased wet‐to‐dry weight ratio, myeloperoxidase activity, serum amylase activity, tnf‐α, interleukin‐1 beta (il‐1β), and intercellular adhesion molecule‐1 (icam‐1) contents, p‐p38mapk, p‐erk1/2, and p‐jnk protein levels as well as pak1 positive expression, while decreased mi r‐542‐5p levels were observed.Functionally, overexpression of mi r‐542‐5p improves ali in mice with sap via inhibition of the mapk signaling pathway by binding to pak1.based on the evidence from experimental models, mi r‐542‐5p was shown to improve ali among mice with sap, while suggesting that the effect may be related to the inactivation of the mapk signaling pathway and downregulation of pak1 gene.Thus, mi r‐542‐5p could serve as a promising target for ali treatment.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
MicroRNA-198 inhibition of HGF/c-MET signaling pathway overcomes resistance to radiotherapy and induces apoptosis in human non–small-cell lung cancer

Non–small‐cell lung cancer (nsclc) is the most common cause of death from cancer worldwide.Micro rnas (mi rnas) are a group of important regulators in nsclc, including mi r‐198.However, the underlying molecular mechanisms of mi r‐198 involvement in intrinsic resistance to radiotherapy in nsclc remain to be elucidated.In this study, to investigate the clinical significance of mi r‐198 in nsclc in relation to the response to radiotherapy, we determined the expression patterns of mi r‐198 between responders and nonresponders after 2 months of radiotherapy and found that decreased expressions of mi r‐198 were associated with radiotherapy resistance.In addition, we altered the endogenous mi r‐198 using mimics or inhibitors to examine the effects of mi r‐198 on 4‐gy–irradiated a549 and spca‐1 cells in vitro.Upregulating mi r‐198 was shown to inhibit cell proliferation, migration, and invasion and induce apoptosis.Mi r‐198 inhibition produced a reciprocal result.Pha665752, a selective small‐molecule c‐met inhibitor, potently inhibited hepatocyte growth factor (hgf)‐stimulated and constitutive c‐met phosphorylation and rescued 4‐gy–irradiated a549 and spca‐1 cells from mi r‐198 inhibition.Most importantly, we established tumor xenografts of 4‐gy–irradiated a549 and spca‐1 cells in nude mice and found that mi r‐198 could suppress tumor formation.Hence, our data delineates the molecular pathway by which mi r‐198 inhibits nsclc cellular proliferation and induces apoptosis following radiotherapy, providing a novel target aimed at improving the radiotherapeutic response in nsclc.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Upregulated microRNA-485 suppresses apoptosis of renal tubular epithelial cells in mice with lupus nephritis via regulating the TGF-β-MAPK signaling pathway by inhibiting RhoA expression

Lupus nephritis (ln) is a common and severe complication of systemic lupus erythematosus.Without intervention, ln may cause acute kidney injury and end‐stage renal disease.This study aims to determine whether micro rna‐485 (mi r‐485) affects renal tubular epithelial cells (rtecs) in ln mice via the tgf‐β‐mapk signaling pathway by targeting rho a .Renal tissue samples were initially extracted from 15 ln and 15 normal mice.Rtecs were cultivated in vitro and grouped after transfection of different mimics, inhibitors, or si rna‐ rho a .The target gene of mi r‐485 was confirmed by dual‐luciferase reporter assay.Flow cytometry and mtt assay were applied to detect cell viability and apoptosis.It was determined that rho a was a target gene of mi r‐485.We found that urine protein, creatinine, rho a, interleukin 6 (il‐6), transforming growth factor‐β1 (tgf‐β1), and p38 mitogen‐activated protein kinases (p38mapk) were highly expressed in renal tissues of ln mice, while poor levels of mi r‐485 were recorded.The overexpression of mi r‐485 or si rna‐ rho a or the combination of mi r‐485 and si rna‐ rho a was demonstrated to lead to a reduction of levels of rho a, il‐6, tgf‐β, and p38mapk, as well as a promotion of rtecs proliferation and inhibition of rtecs apoptosis.Taken together, these findings indicated that overexpressed mi r‐485 downregulates rho a which could promote cell viability and inhibit apoptosis of rtecs by regulating the rho a‐mediated tgf‐β‐mapk signaling pathway in ln mice.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
EBF1 gene promotes the proliferation and inhibits the apoptosis of bone marrow CD34+cells in patients with myelodysplastic syndrome through negative regulation of mitogen-activated protein kinase axis

The transcription factor, early b cell factor 1 (ebf1), plays a vital role in the lineage specification involving early b cell development and the onset of myelodysplastic syndrome (mds).Therefore, to investigate whether or not ebf1 affects mds as well as the transcription factor's underlying mechanism, we used cd34+ hematopoietic stem cells in bone marrow from patients with mds.The extracted cells were then transfected with a series of ebf1, short hairpin rna against ebf1 (sh ebf1), and sb203580 (a specific mitogen‐activated protein kinase [mapk] axis inhibitor).The effects ebf1 gene and mapk axis had on cell proliferation, apoptosis, and migration were determined by in vitro cell culturing.We made observations that involved ebf1 inhibiting the messenger rna (m rna) level of p38 mapk, increasing the m rna levels of extracellular‐signal–regulated kinase (erk), c‐jun n‐terminal kinase (jnk), extracellular‐signal–regulated kinase 5 (erk5), decreasing the protein expression of bcl‐2–associated x protein (bax), and finally elevating the protein levels of b cell lymphoma/leukemia‐2 (bcl‐2), stem cell factor (scf), erythropoietin receptor (epo r), p‐erk, p‐jnk, p‐erk5, cyclin d, cyclin e, cyclin‐dependent kinase 2 (cdk2), and cdk6, implying that ebf1 may very well have an inhibitory role in the mapk axis.Another discovery found that ebf1 had a positive effect on the promotion of bone marrow cd34+ cell proliferation as well as its migration, but inhibited the apoptosis of cells.The results we obtained from this study indicated that the ebf1 gene suppresses the activation of the mapk axis, thereby promoting both the proliferation and migration of bone marrow cd34+ cells as well as inhibiting the associating apoptosis.The effects of the ebf1 gene are likely to present a new therapeutic target in preventing the progression of mds.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Effects of RNA interference–mediated E-selectin gene silencing on cell adhesion molecule expression and cell-cell adhesion in vascular endothelial cells in mice with immunologic contact urticaria

Contact urticaria is recognized as the wheal and flare reaction at a site from direct contact with a chemical or protein agent.Ongoing studies have proposed that gene silencing may have a promising future in finding optimal treatment of a variety of disease; hence, the aim of the study was to investigate the effect of rna interference–mediated e‐selectin ( sele ) gene silencing on cell adhesion molecule expression and on cell‐cell adhesion in vascular endothelial cells (vecs) in a mouse model of immunologic contact urticaria (icu).Following the successful establishment of mouse models of icu induced by antidinitrophenol immunoglobulin e (ig e) combining 2,4‐dinitrofluorobenzene challenge, enzyme‐linked immunosorbent assay and immunohistochemistry were used to measure the levels of ig e, interleukin 4 (il‐4), interferon‐γ (ifn‐γ), and histamine as well as the positive expression rate of sele, respectively.The si rna‐ sele vector was constructed and transfection efficiency was estimated prior to performing quantitative reverse‐transcription polymerase chain reaction and western blot assay to determine the relative expression of sele, eosinophil cationic protein (ecp), intercellular adhesion molecule 1 (icam‐1), l‐selectin (cd62l), and the alpha chain of leukocyte function–associated antigen‐1 (cd11a).Adhesion assay was then performed to assess the cell adhesion ability in vecs.Elevated levels of ig e, il‐4, ifn‐γ, and histamine and increased positive expression rate of sele were indicative of successful establishment of mouse models of icu.Furthermore, the relative expression levels of sele, ecp, icam‐1, cd62l, and cd11a were highest in the oe‐ sele group.Besides, cell adhesion ability of vecs was notably promoted.Collectively, the current study define the potential role of sele silencing as an inhibitor to icu development by inhibiting cell adhesion ability of vecs.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Platelet-derived growth factor subunit B is required for tendon-bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

As a common cause of shoulder pain and disability, rotator cuff injury (rci) represents a debilitating condition affecting an individual’s quality of life.Although surgical repair has been shown to be somewhat effective, many patients may still suffer from reduced shoulder function.The aim of the current study was to identify a more effective mode of rci treatment by investigating the effect of platelet‐derived growth factor subunit b (pdgf‐b) on tendon‐bone healing after rci repair by modifying bone marrow–derived mesenchymal stem cells (bmscs).Surface markers of bmscs were initially detected by means of flow cytometry, followed by establishment of the rat models and construction of the lentiviral vector.3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐h‐tetrazolium bromide, thiazolyl blue tetrazolium bromide (mtt) assay, alizarin red staining, and oil red o staining were used to provide verification that pdgf‐b was indeed capable of promoting bmsc viability, osteogenic and adipogenic differentiation capability.Furthermore, biomechanical assessment results indicated that pdgf‐b could increase the ultimate load and stiffness of the tendon tissue.Real‐time reverse‐transcription quantitative polymerase chain reaction and western blot analysis methods provided evidence suggesting that pdgf‐b facilitated the expression of tendon‐bone healing–related genes and proteins, while contrasting results were obtained after pdgf‐b silencing.Taken together, the key findings of the current study provided evidence suggesting that overexpressed pdgf‐b could act to enhance tendon‐bone healing after rci repair, thus highlighting the potential of the functional promotion of pdgf‐b as a future rci therapeutic approach.

Journal: Journal of Cellular Biochemistry (2017)
Publication types: Research Article;
Inhibition of Notch signaling pathway enhanced the radiosensitivity of breast cancer cells

This study aimed to investigate the effect of inhibiting the notch signaling pathway on the radiosensitivity of breast cancer cells.Human breast cancer cell lines (mcf‐7 and t47d) were selected and treated with radiation of different doses.Cells were treated with gamma secretase inhibitor (gsi) to analyze the effects of gsi on the notch signaling, which were detected by immunofluorescence assay, rt‐q pcr, and western blot analysis.Besides, transwell assay, scratch test, colony formation assay, mtt assay, and flow cytometry were conducted to show the effects of gsi on the invasion and migration, survival fraction, cell viability, and apoptosis of mcf‐7 and t47d cells after radiation therapy.Moreover, cell transfection with a dominant negative mutant of rbpj, the key transcription factor of notch signaling pathway, were also applied to show the inhibition of notch signaling pathway.Initially, we found that the 4 gy radiation activated notch signaling pathway, and enhanced the invasion and migration of mcf‐7 and t47d cells.However, gsi inhibited the notch signaling pathway, and reversed the enhancement of radiation on the migration and invasion, promoted the enhancement of apoptosis and inhibition of proliferation of mcf‐7 and t47d cells induced by radiation.Except that, we also determined that gsi and dn rbpj suppressed the upregulation of notch signaling after radiation therapy.Our study demonstrated that inhibition of the notch signaling pathway enhanced the radiosensitivity of breast cancer cells, which may provide evident for a beneficial adjuvant therapy in the breast cancer treatment.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;