syedzayyan/paper_mill_benchmark huggingface dataset:
microRNA-155 Modulates Hepatic Stellate Cell Proliferation, Apoptosis, and Cell Cycle Progression in Rats With Alcoholic Hepatitis via the MAPK Signaling Pathway Through Targeting SOCS1

The aim of this study was to investigate the regulatory function of the non-coding micro rna-155 (mi r-155) and suppressor of cytokine signaling 1 (socs1) in alcoholic hepatitis (ah) and its potential mechanism associated with the mitogen-activated protein kinase (mapk) signaling pathway.Levels of alanine aminotransferase (alt), aspartate aminotransferase (ast), albumin (alb), total bilirubin (tbil), malondialdehyde (mda), and superoxide dismutase (sod) were measured in a rat model of ah.The biological prediction website micro rna.org and dual-luciferase reporter gene assay were used to identify whether socs1 was a direct target of mi r-155, and the effects of mi r-155 and socs1 on the viability, cycle progression, and apoptosis of hepatic stellate cells were assessed using rt-q pcr, western blot assay, mtt assay, annexin v/pi double staining, and pi single staining.The levels of alt, ast, mda, and tbil and the liver cell morphology were all prominently changed in ah model rats.Mi r-155 suppressed socs1 by specifically binding to socs1-3’-utr to activate the mapk signaling pathway.Socs1 had low expression while mi r-155 was highly expressed in ah rats.Mi r-155 promoted hepatic stellate cell viability and cycle progression and reduced cell apoptosis by silencing socs1.Together, we find that silenced mi r-155 could upregulate socs1 and inactivate the mapk signaling pathway, thereby inhibiting the proliferation of alcoholic hepatic stellate cells and promoting cell apoptosis.

Journal: Frontiers in Pharmacology (2020)
Publication types: Research Article;
Bactericidal/Permeability-Increasing Protein Improves Cognitive Impairment in Diabetic Mice via Blockade of the LPS-LBP-TLR4 Signaling Pathway

Emerging evidence suggests that the bactericidal/permeability-increasing protein (bpi) is involved in the process of cognitive impairment in diabetes.However, its underlying mechanism remains elusive.In this study, we found that bpi affects cognitive impairment due to diabetes through the lipopolysaccharide (lps)-lipopolysacharide-binding protein (lbp)-toll-like receptor 4 (tlr4) signaling pathway.We examined the expression of bpi, lps, lbp, cd14, and tlr4 in established mouse models of diabetes induced by high-fat diet (hfd) in combination with streptozotocin (stz).Diabetic mice were then injected with adeno-associated-virus carrying bpi overexpression vectors and lps.Fasting blood glucose, plasma insulin, and serum levels of inflammatory factors were examined.Then, glucose tolerance and, insulin resistance tests were used to measure systemic insulin sensitivity.Next, hippocampal tissue injury and cell apoptosis were examined by hematoxylin-eosin (he) and terminal deoxynucleotidyl transferase-mediated d utp-biotin nick end labeling (tunel) staining.Diabetic mice displayed increased lps expression and activation of the lps-cd14-tlr4 signaling pathway.Hfd mice following lps treatment showed significantly increased serum levels of tumor necrosis factor-α (tnf-α), interleukin (il)-1β, and il-6, and expressions of bcl-2-associated x protein (bax) and aβ but decreased expression of bcl-2 in hippocampal tissues, as well as enhanced fasting blood glucose, plasma insulin, glucose tolerance, insulin tolerance, cell apoptosis, aggravated hippocampal tissue injury and, ultimately, cognitive impairment.However, overexpression of bpi was able to rescue the aforementioned phenotypes driven by lps treatment.Taken together, bpi could potentially provide relief from cognitive impairment in diabetic mice by disrupting the lps-lbp-tlr4 signaling pathway, underscoring a possible alternative therapeutic strategy against the cognitive impairment associated with diabetes.

Journal: Frontiers in Physiology (2021)
Publication types: Research Article;
Downregulation of hsa_circ_0001836 Induces Pyroptosis Cell Death in Glioma Cells via Epigenetically Upregulating NLRP1

It has been shown that circular rnas (circ rnas) play a vital role in the progression of glioma.Recently, hsa_circ_0001836 was found to be upregulated in glioma tissues, but the role of hsa_circ_0001836 in glioma remains unclear.Methods ed u staining and flow cytometry assays were used to measure the viability and death of glioma cells.In addition, scanning electron microscopy (sem) was used to observe the morphology of cells undergoing cell death.Results hsa_circ_0001836 expression was upregulated in u251mg and shg-44 cells.In addition, hsa_circ_0001836 knockdown significantly reduced the viability and proliferation of u251mg and shg-44 cells.Moreover, hsa_circ_0001836 knockdown markedly induced the pyroptosis of u251mg and shg-44 cells, evidenced by the increased expressions of nlrp1, cleaved caspase 1 and gsdmd-n.Meanwhile, methylation specific pcr (msp) results indicated that hsa_circ_0001836 knockdown epigenetically increased nlrp1 expression via mediating dna demethylation of nlrp1 promoter region.Furthermore, downregulation of hsa_circ_0001836 notably induced pyroptosis and inhibited tumor growth in a mouse xenograft model of glioma.Conclusion collectively, hsa_circ_0001836 knockdown could induce pyroptosis cell death in glioma cells in vitro and in vivo via epigenetically upregulating nlrp1 expression.These findings suggested that hsa_circ_0001836 may serve as a potential therapeutic target for the treatment of glioma.

Journal: Frontiers in Oncology (2021)
Publication types: Research Article;
miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5

Emerging evidence indicates that micro rna (mi r)-193a-3p is involved in the tumor progression of various cancers.However, the biological functions and precise molecular mechanisms of mi r-193a-3p in gliomas have not been well documented.Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of mi r-193a-3p in glioma cells.Mi r-193a-3p expression was determined by q rt-pcr in glioma tissues and cell lines.U251 and u87 glioma cells were transfected with a mi r-193a-3p mimic.The effects of mi r-193a-3p on cell growth and apoptosis were investigated using mtt, colony-forming, and flow cytometry assays.Overexpression of mi r-193a-3p in u87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model.Luciferase assays were conducted to determine if alkbh5 is a direct target of mi r-193a-3p in glioma cells.Immunoprecipitation was used to explore the interaction between alkbh5 and rac-serine/threonine-protein kinase 2 (akt2) in glioma cells.Mi r-193a-3p was downregulated in glioma tissues and cell lines.Mi r-193a-3p treatment suppressed proliferation and promoted apoptosis in both u251 and u87 cells.Bioinformatics analysis and luciferase reporter assay identified a novel mi r-193a-3p target, alkbh5.Notably, the antitumor effect of mi r-193a-3p transfection in glioma cells may be due to the mi r-193a-3p–induced inhibition of akt2 expression caused by the suppression of alkbh5 expression.Furthermore, immunoprecipitation indicated that alkbh5 physically interacted with akt2 through an rna-independent mechanism in glioma cells.Mi r-193a-3p directly targets alkbh5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the akt2 pathway both in vitro and in vivo , and the physical interaction between alkbh5 and akt2 is essential for suppressing cell apoptosis by upregulating mi r-193a-3p in glioma cells.Our study revealed that the antitumor effects of mi r-193a-3p on glioma cells is due to alkbh5 mediation of the akt2-induced intrinsic apoptosis signaling pathway.

Journal: Frontiers in Oncology (2021)
Publication types: Research Article;
LncRNA SNHG19 Promotes the Development of Non-Small Cell Lung Cancer via Mediating miR-137/E2F7 Axis

Non-small cell lung cancer (nsclc) is a common malignant tumor, which has high incidence and low the 5-year survival rate.Long non-coding rnas (lnc rnas) play critical roles in carcinoma occurrence and metastasis.Herein, our aim was to investigate the effects of lnc rna snhg19 in nsclc progression.Materials and methods long non-coding rna small nucleolar rna host gene 19 (lnc rna snhg19) expression level was measured by bioinformatics and q rt-pcr.Edu, transwell, and scratch assays were performed to explore the role of si-snhg19 or snhg19 on nsclc progression.Luciferase assay was used to verify the relationship between snhg19/e2f7 and mi r-137.The experiment of xenograft was used for exploring the function of snhg19 in vivo .Results snhg19 was upregulated in cancer tissues, patients plasma and cell lines of nsclc.Knockdown of snhg19 inhibited cell proliferation, migration, and invasion.Luciferase assay confirmed that snhg19 regulated e2f7 expression via interacting with mi r-137.Overexpression of snhg19 accelerated nsclc tumor progression via mi r-137/e2f7 axis both in vitro and in vivo .Conclusions our results clarified the snhg19 function for the first time, and snhg19 promoted the progression of nsclc, which was mediated by the mi r-137/e2f7 axis.This study might provide new understanding and targets for nsclc diagnosis and treatment.

Journal: Frontiers in Oncology (2021)
Publication types: Research Article;
lncRNA-XLOC_012370 Promotes the Development of Pancreatic Cancer and Inactivates the NF-κB Pathway Through miR-140-5p

Pancreatic cancer is a high incidence, high degree of malignancy, and high mortality in the digestive system tumor.The incidence of pancreatic cancer in china has increased nearly six folds in the past 20 years, ranking fifth in the mortality rate of malignant tumors, so it is particularly important to actively explore clinical indicators with better diagnostic significance for pancreatic cancer.Lnc rna performs an essential regulatory function in the occurrence, development, and metastasis of many kinds of tumors, playing both a carcinogenic role and a tumor suppressor gene.Here, we demonstrated the function and mechanism of lnc rna-xloc_012370 in the development of pancreatic cancer.In our research, the abnormal upregulation of xloc_012370 was observed in pancreatic cancer patients’ tumor tissues.Xloc_012370 was related to tumor stage, lymph node metastasis, and overall survival.Silencing of xloc_012370 prevented the proliferation, migration, and invasion via the nf-κb signal pathway.Further, mi r-140-5p was identified as the target and downstream of xloc_012370 and involved in pancreatic cancer progression.In vivo , knockdown of xloc_012370 inhibited tumor growth via the nf-κb signal pathway.In conclusion, lnc rna-xloc_012370 is closely related to some malignant clinicopathological features and prognosis of pancreatic cancer.Thus the mi r-140-5p/nf-κb signal pathway might represent a promising treatment strategy to combat pancreatic cancer.

Journal: Frontiers in Oncology (2021)
Publication types: Research Article;
LINC00337 Regulates KLF5 and Maintains Stem-Cell Like Traits of Cervical Cancer Cells by Modulating miR-145

Accumulating literature and evidence has highlighted the cancer stem-like cell (csc) model as a cellular mechanism responsible for the phenotypic heterogeneity observed in various types of cancers, including cervical cancer.Long non-coding rnas (lnc rnas) have been implicated in the retention of stem cell-like traits in cancer cells.However, the role of lnc rnas in the acquisition and maintenance of cscs in cervical cancer remains largely unknown.Hence, the current study identified that linc00337 knockdown diminished the csc-like properties of cd44 + /cd24 low/− sfcs, evidenced by a decline in the generation of tumorospheres and colonies, a reduction in multi-drug resistance gene-1 (mdr-1), nanog, sox2, and oct4 expression, along with an enhancement in cell apoptosis.Rna pull-down assays and rna immunoprecipitation revealed the role of linc00337 as a competing endogenous rna (ce rna) of micro rna-145 (mi r-145).Furthermore, the mi r-145 m rna target, kruppel-like factor 5 (klf5), was decreased in cd44 + /cd24 low/− sfcs upon linc00337 knockdown.The in vitro results were reproduced in in vivo studies, which provided verification attesting that linc00337 knockdown attenuated the tumorigenicity of cd44 + /cd24 low/− sfcs in nude mice.Taken together, the key findings of the current study demonstrate that linc00337 acts as an oncogenic lnc rna in cervical cancer and exerts its influence on the expression of klf5 and the maintenance of cancer stem cell-like properties by means of downregulating mi r-145.

Journal: Frontiers in Oncology (2020)
Publication types: Research Article;
LncRNA DLX6-AS1 Promotes Malignant Phenotype and Lymph Node Metastasis in Prostate Cancer by Inducing LARGE Methylation

Long non-coding rnas (lnc rnas) have recently become recognized as crucial players in cancer cellular events including proliferation, migration, and invasion.Herein, we investigated the potential role of lnc rna dlx6-as1 in prostate cancer cell malignant behaviors and lymph node metastasis.A differentially expressed lnc rna dlx6-as1 and its downstream regulatory gene (large) were predicted by analysis in silico .Rt-q pcr and western blot analysis results demonstrated that dlx6-as1 was highly expressed, but large was poorly expressed in prostate cancer tissues and cells.The online website indicated that dlx6-as1 negatively targeted large expression, which was validated by pearson correlation analysis and msp.Ch ip, rip, and rna pull-down assays further suggested that dlx6-as1 downregulated large expression through recruitment of dnmt1 to its promoter.We induced dlx6-as1/large overexpression or knockdown to examine their effects through edu and transwell assays, which revealed that dlx6-as1 overexpression accelerated proliferation, invasion, and migration of prostate cancer cells, and that overexpression of large rescued these effects.Tumors xenografts studies confirmed that dlx6-as1 promoted lymph node metastasis by regulating large, as evidenced by enhanced expression of mmp-9, u par, and cathepsin b.In summary, dlx6-as1 stimulated prostate cancer malignant progression and lymph node metastasis by inducing dnmt1-mediated large methylation, highlighting a potential therapeutic target against prostate cancer.

Journal: Frontiers in Oncology (2020)
Publication types: Research Article;
Exosomal MicroRNA-221-3p Confers Adriamycin Resistance in Breast Cancer Cells by Targeting PIK3R1

Drug resistance in breast cancer (bc) cells continues to be a stern obstacle hindering bc treatment.Adriamycin (adr) is a frequently employed chemotherapy agent used to treat bc.The exosomal transfer of micro rnas (mi rnas) has been reported to enhance the drug-resistance of bc cells.Herein, we first sought to elucidate the possible role of the exosomal transfer of mi r-221-3p in the drug resistance of mcf-7 cells to adr.Differentially expressed genes (degs) were initially screened through microarray analysis in bc drug resistance-related datasets.Next, the expression of mi r-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1) was quantified in adr-resistant mcf-7 (mcf-7/adr) and adr-sensitive mcf-7 (mcf-7/s) cell lines, after which exosomes were separated and identified in each cell line.Target relationship between mi r-221-3p and pik3r1 was validated by a dual-luciferase reporter assay.Next, the expression of mi r-221-3p and pik3r1 was altered to clarify their effects on the resistance of mcf-7 cells to adr in vitro and in vivo .Pik3r1 was identified as a bc drug resistance-related deg, with the regulatory mi r-221-3p subsequently obtained.Moreover, the mcf-7/adr cells exhibited a low expression of pik3r1 and a high expression of mi r-221-3p.Notably, pik3r1 was identified as a target gene of mi r-221-3p.The overexpression of mi r-221-3p in mcf-7/adr cell-derived exosomes promoted adr resistance in mcf-7/s cells via the pi3k/akt signaling pathway.The in vitro results were reproducible in in vivo assays.Taken together, drug-resistant bc cell-derived exosomal mi r-221-3p can promote the resistance of bc cells to adr by targeting pik3r1 via the pi3k/akt signaling pathway in vitro and in vivo .These findings provide encouraging insights and provide perspectives for further investigation into the bc drug resistance mechanism.

Journal: Frontiers in Oncology (2020)
Publication types: Research Article;
MicroRNA-27 Inhibits Autophagy and Promotes Proliferation of Multiple Myeloma Cells by Targeting the NEDD4/Notch1 Axis

Multiple myeloma (mm) is a malignant tumor disease that seriously affects the health of patients.Previous studies have shown the crucial role of autophagy in the development of mm.Therefore, the study aimed to study the effect of mi r-27 on autophagy in mm via nedd4/notch1 axis.Rt-q pcr or western blot analysis was used to detect the expression of mi r-27, nedd4, and notch1 in bone marrow tissues and cd138+ plasma cells of patients and mm cells.After gain- and loss-of-function assays in mm cells, proliferation and invasion were assessed by clone formation and transwell assays.Meanwhile, expression of autophagy-related proteins was measured by western blot analysis, followed by evaluation of autophagosomes and autophagic flow.The targeting relationship was evaluated by luciferase reporter assay, whereas the binding of nedd4 to notch1 protein was analyzed by co-immunoprecipitation.The ubiquitination level of notch1 protein was detected.A nude mouse tumor model was established to determine the role of mi r-27 in mm in vivo .Mi r-27 and notch1 upregulation and nedd4 downregulation were observed in bone marrow tissues and cd138+ plasma cells of patients and mm cells.Mi r-27 negatively targeted nedd4, while nedd4 could specifically bind to notch1 protein to increase notch1 ubiquitin degradation in mm cells.Mi r-27 or notch1 overexpression or nedd4 silencing diminished autophagy but enhanced proliferation and invasion of mm cells.Mi r-27 upregulation promoted the formation of subcutaneous tumor in nude mice.Collectively, mi r-27 elevated notch1 expression by targeting nedd4 and promoted the development of mm by inhibiting cell autophagy, which provides a new idea and basis for mm treatment.

Journal: Frontiers in Oncology (2020)
Publication types: Research Article;
Overexpression of microRNA-216a-3p Accelerates the Inflammatory Response in Cardiomyocytes in Type 2 Diabetes Mellitus by Targeting IFN-α2

Type 2 diabetes mellitus (t2dm) is a chronic, hyperglycemia-associated, metabolic disorder.Heart disease is a major complication of t2dm.The present study aimed to explore the effects of mi r-216a-3p on cardiomyocyte proliferation, apoptosis, and inflammation in t2dm through the toll-like receptor (tlr) pathway involving interferon-α2 (ifn-α2) mediation.Methods: t2dm was induced in rats by a high-fat diet, in combination with an intraperitoneal injection of low-dose streptozotocin.Elisas were conducted to measure inflammatory-related factors in serum.Next, isolated cardiomyocytes were used in loss- and gain-of-function experiments, followed by mtt and flow cytometry assays, conducted to evaluate cell proliferation, cell cycle, and apoptosis.Results: our results revealed an increase in the inflammatory response in t2dm rat models, accompanied by significantly increased expression of mi r-216a-3p and tlr pathway-related genes.However, a decrease in the expression of ifn-α2 was observed.Moreover, the presence of an mi r-216a-3p inhibitor and si-ifn-α2 increased the expression of tlr pathway-related genes and cell apoptosis, whereas cell proliferation was significantly decreased in the cardiomyocytes.Conclusion: we found that in t2dm, mi r-216a-3p inhibited the proliferation and enhanced the apoptosis of cardiomyocytes and generated an inflammatory response through activation of the tlr pathway and targeting of ifn-α2.

Journal: Frontiers in Endocrinology (2020)
Publication types: Research Article;
Allopregnanolone restores the tyrosine hydroxylase-positive neurons and motor performance in a 6-OHDA-injected mouse model

Aims it has been reported that allopregnanolone (apα) promotes the neurogenesis of the neural progenitor cells (npcs) in the subventricular zone (svz) and prevents the decrease of dopaminergic neurons in 6‐hydroxydopamine (6‐ohda)‐treated mice by binding to γ‐aminobutyric acid a receptor (gabaar) and then opening voltage‐gated l‐type ca 2+ channel, but the underlying mechanisms remain elusive.The aim of this study was to explore the possible involvement of gabaar and calcium/calmodulin‐dependent protein kinase ii delta 3 (ca mkiiδ3) in this process.Methods 6‐ohda‐treated mice and primary cultured midbrain cells were administrated with apα and gabaar antagonist bicuculline (bic), and the proliferation and differentiation of npcs, the tyrosine hydroxylase (th)‐positive neurons and their fibers, the expression levels of ca mkiiδ3 and brain‐derived neurotrophic factor (bdnf), and motor functions were measured using elisa, immunohistochemical staining, real‐time rt‐pcr, western blot, and behavioral test.Results allopregnanolone significantly promoted the phosphorylation of cytoplasmic ca mkiiδ3 and its nuclear translocation by binding to gabaar, which, in turn, increased the expression levels of bdnf.This may account for the findings that the exogenous apα enhanced the proliferation and differentiation of npcs, and ameliorated the nigrostriatal system and behavioral performance in 6‐ohda‐treated mice.Conclusions allopregnanolone may directly activate gabaar, which, in turn, enhance the proliferation and differentiation of npcs via upregulating the expression levels of ca mkiiδ3, and finally contribute to the restoration of dopaminergic neurons in 6‐ohda‐treated mice.

Journal: CNS Neuroscience & Therapeutics (2020)
Publication types: Research Article;
Long non-coding RNA XIST binding to let-7c-5p contributes to rheumatoid arthritis through its effects on proliferation and differentiation of osteoblasts via regulation of STAT3

Background rheumatoid arthritis (ra), a chronic autoimmune disease, affects around 1% population worldwide, with the life quality of patients severely reduced.In this study, it is intended to explore the role of long non‐coding rna x‐inactive specific transcript (lnc rna xist) in ra and the underlying mechanisms associated with let‐7c‐5p and signal transducer and activator of transcription 3 (stat3).Methods lnc rna xist, let‐7c‐5p, and stat3 expressions were determined in ra and normal cartilage tissues, and their relationship was analyzed in osteoblasts.The regulatory effects of lnc rna xist in ra were investigated when xist expression was upregulated or downregulated in osteoblasts.Tnf‐α, il‐2, il‐6, alkaline phosphatase (alp), osteocalcin, tgf‐β1, and igf1 were measured in vivo in ra rats.Results lnc rna xist and stat3 were expressed at high levels and let‐7c‐5p expressed at a low level in ra cartilage tissues.Lnc rna xist silencing or let‐7c‐5p enhancement led to decreased levels of tnf‐α, il‐2, and il‐6, suggestive of suppressed inflammatory response, and increased levels of alp, osteocalcin, tgf‐β1, and igf‐1 as well as reduced damage in cartilage tissues.Conclusion lnc rna xist downregulation could promote proliferation and differentiation of osteoblasts in ra, serving as a future therapeutic target for ra.

Journal: Journal of Clinical Laboratory Analysis (2020)
Publication types: Research Article;