syedzayyan/paper_mill_benchmark huggingface dataset:
Protective effects of microRNA-431 against cerebral ischemia-reperfusion injury in rats by targeting the Rho/Rho-kinase signaling pathway

This study investigates the protective effects of mi r‐431 against cerebral ischemia‐reperfusion injury through the rho/rho‐kinase signaling pathway.Sd rats were randomly classified into normal, sham, and model (middle cerebral artery occluded) groups.Rho expression and cerebral infarction were visualized by immunohischemistry and ttc staining, respectively.Q rt‐pcr and western blotting were used to measure m rna and protein expression of mi r‐431 and rho/rho‐kinase signaling pathway‐related genes.Hippocampal neurons were extracted and assigned into normal, blank, negative control (nc), mi r‐431 mimics, mi r‐431 inhibitors, si rna‐rho, and mi r‐431 inhibitors + si rna‐rho groups.Proliferation and apoptosis were detected by mtt and flow cytometry, respectively.Compared with the normal group, the model group showed elevated rho expression, area of cerebral infarction, and expressions of rho/rho‐kinase related genes but reduced mi r‐431 expression.Compared with the blank group, expression of rho, rho‐kinase α, and rho‐kinase β decreased and mi r‐431 expression increased in the mi r‐431 mimics and si rna‐rho groups, and the tendency reversed in the mi r‐431 inhibitors group.Enhanced proliferation and inhibited apoptosis were exhibited in the mi r‐431 mimics and si rna‐rho groups while results in the mi r‐431 inhibitors group reversed.Findings obtained from this study indicated that mi r‐431 confers protection against cerebral ischemia‐reperfusion injury through negatively regulating the rho/rho‐kinase signaling pathway.

Journal: Journal of Cellular Physiology (2017)
Publication types: Research Article;
MicroRNA-30d preserves pancreatic islet β-cell function through negative regulation of the JNK signaling pathway via SOCS3 in mice with streptozotocin-induced diabetes mellitus

The loss of pancreatic islet β‐cell function represents the classical feature in the pathogenesis of type 2 diabetes mellitus (t2dm).Previous evidence has highlighted the involvement of the activated jnk pathway in relation to islet β‐cell apoptosis.Hence, during the present study a streptozotocin‐induced dm mice model was established in a bid to ascertain as to whether micro rna‐30d (mi r‐30d) plays a regulatory role in the jnk pathway in relation to islet β‐cell dysfunction.The collection and identification of the islet β cells from streptozotocin‐induced mice was performed.Islet β cells with elevated or suppressed levels of mi r‐30 as well as knocked down socs3 were established in order to verify the regulatory mechanisms by which mi r‐30d governs socs3 in vitro.We found mi r‐30d was overexpressed among tissue samples obtained form streptozotocin‐induced mice and their islet β cells, as well as increasing mi r‐30d expression when the jnk pathway was activated were found to promote islet β cell growth and cell cycle entry, and inhibit apoptosis.Socs3, confirmed to be a mi r‐30d target, was decreased in the islet β cells following the promotion of mi r‐30d, while the jnk pathway was inhibited following socs3 knocdown.Furthermore, the effect of mi r‐30d inhibition was lost in islet β cells when socs3 was knocked down.The data of the present study support the notion that mi r‐30d‐mediated direct suppression of socs3 acts to protect pancreatic β‐cell functions through the jnk signaling pathway, emphasizing the potential of mi r‐30d as a novel pharmacological target for treatment and intervention of dm.

Journal: Journal of Cellular Physiology (2018)
Publication types: Research Article;
MicroRNA-219 decreases hippocampal long-term potentiation inhibition and hippocampal neuronal cell apoptosis in type 2 diabetes mellitus mice by suppressing the NMDAR signaling pathway

Summary objective type 2 diabetes mellitus (t2 dm ) is a complex polygenic disease that causes hyperglycemia and accounts for 90%‐95% of all diabetes mellitus cases.Hence, this study aimed to examine the effects of micro rna ‐219 (mi r‐219) on inhibition of long‐term potentiation ( ltp ) and apoptosis of hippocampal neuronal cells in t2 dm mice through the n‐methyl‐d‐aspartate receptor ( nmdar ) signaling pathway regulation.Methods the t2 dm mouse models were established, after which ltp in vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured.Next, the density of pyramidal neurons in each group was calculated.Additionally, the expression levels of mi r‐219, the nmdar signaling pathway [ nmdar 1 ( nr ) 1, nr 2a, and nr 2b), downstream target proteins [calmodulin‐dependent protein kinase‐ ii (ca mk ‐ ii ) and c amp response element binding protein ( creb )], and apoptosis‐related factors [bcl2‐associated x protein (bax), c‐caspase‐9 and c‐caspase‐3] in the hippocampal tissues were determined.Finally, immunohistochemistry was applied to detect and measure the positive expression of bax, caspase‐9, and caspase‐3 proteins.Results the results showed that upregulation of mi r‐219 increases ltp and density of pyramidal neurons in the hippocampal tissues of mice, while it decreases blood glucose of db/db mice.In addition, mi r‐219 upregulation also leads to decreased m rna levels of nr 1, nr 2a, nr 2b, ca mk ‐ ii , and creb and protein levels of nr 1, nr 2a, nr 2b, ca mk ‐ ii , creb , p‐ creb , bax, c‐caspase‐9, and c‐caspase‐3.Furthermore, upregulation of mi r‐219 inhibits positive expression of bax, caspase‐9, and caspase‐3 proteins, leading to the suppression of hippocampal neuronal cell apoptosis.Conclusion the findings from this study indicated that the upregulation of mi r‐219 decreases ltp inhibition and hippocampal neuronal cell apoptosis in t2 dm mice by downregulating the nmdar signaling pathway, therefore suggesting that mi r‐219 might be a future therapeutic strategy for t2 dm .

Journal: CNS Neuroscience & Therapeutics (2018)
Publication types: Research Article;
MicroRNA-92a promotes tumor growth and suppresses immune function through activation of MAPK/ERK signaling pathway by inhibiting PTEN in mice bearing U14 cervical cancer

Cervical cancer is known as the possible outcome of genital infection, while the molecular mechanisms of initiation, development, and metastasis of cervical cancer have not yet been fully elucidated.Our study aims to investigate the effects of micro rna ‐92a (mi r‐92a) on tumor growth and immune function by targeting pten via the mapk / erk signaling pathway in tumor‐bearing mice.C57 bl /6 female mice were used for tumor‐bearing mouse models and their tumor and adjacent normal tissues were collected, and normal cervical tissues were obtained from normal mice.Serum levels of tumor necrosis factor‐ α ( tnf ‐ α ) and soluble interleukin‐2 receptor ( s il ‐2r) were detected by elisa .The cells were divided into the normal, blank, negative control ( nc ), mi r‐92a mimic, mi r‐92a inhibitor, si rna ‐ pten , and mi r‐92a inhibitor + si rna ‐ pten groups.Dual‐luciferase reporter assay was adopted to determine the relationship between pten and mi r‐92a.Expressions of mi r‐92a, pten , tnf ‐ α , s il ‐2r, erk 1, and erk 2 were tested by rt ‐ q pcr and western blotting.Cell proliferation was detected by cell count kit‐8 ( cck ‐8); cell cycle and apoptosis were detected by flow cytometry.Compared with the normal cervical tissues and adjacent normal tissues, the cervical cancer tissues exhibited increased expressions of mi r‐92a, p‐ erk 1/2, and serum levels of tnf ‐ α and s il ‐2r while decreased pten expression.Pten was confirmed to be the target gene of mi r‐92a.As compared with the blank and nc groups, expressions of mi r‐92a, erk 1 and erk 2 increased, and expressions of pten decreased in the mi r‐92a mimic group.The mi r‐92a mimic group exhibited increased expression levels of tnf ‐ α and s il ‐2r, cell proliferation, and cell number in s phase but decreased cell apoptosis, and cell number in g0/g1 phase, while the mi r‐92a inhibitor group followed opposite trends.Mi r‐92a promotes tumor growth and suppresses immune function by inhibiting pten via activation of the mapk / erk signaling pathway in mice bearing u14 cervical cancer.

Journal: Cancer Medicine (2018)
Publication types: Research Article;
The silencing of long non-coding RNA ANRIL suppresses invasion, and promotes apoptosis of retinoblastoma cells through ATM-E2F1 signaling pathway

As one of the most common primary intraocular carcinomas, retinoblastoma generally stems from the inactivation of the retinoblastoma rb1 gene in retinal cells.Antisense non-coding rna in the ink4 locus (anril), a long non-coding rna (lnc rna), has been reported to affect tumorigenesis and progression of various cancers, including gastric cancer and non-small cell lung cancer.However, limited investigations emphasized the role of anril in human retinoblastoma.Hence, the current study was intended to investigate the effects of anril on the proliferation, apoptosis, and invasion of retinoblastoma hxo-rb44 and y79 cells.The lentivirus-based packaging system was designed to aid the up-regulation of anril and atm expressions or employed for the down-regulation of anril in human retinoblastoma cells.Afterward, anril expression, m rna and protein expression of atm and e2f1, and protein expression of ink4b, ink4a, alternate reading frame (arf), p53 and retinoblastoma protein (p rb) were determined in order to elucidate the regulation effect associated with anril on the atm-e2f1 signaling pathway.In addition, cell viability, apoptosis, and invasion were detected accordingly.The results indicated that the down-regulation of anril or up-regulation of atm led to an increase in the expressions of atm, e2f1, ink4b, ink4a, arf, p53, and p rb.The silencing of anril or up-regulation of atm exerted an inhibitory effect on the proliferation and invasion while improving the apoptosis of hxo-rb44 and y79 cells.In conclusion, the key observations of our study demonstrated that anril depletion could act to suppress retinoblastoma progression by activating the atm-e2f1 signaling pathway.These results provide a potentially promising basis for the targetted intervention treatment of human retinoblastoma.

Journal: Bioscience Reports (2018)
Publication types: Research Article;
Long non-coding RNA HAL suppresses the migration and invasion of serous ovarian cancer by inhibiting EMT signaling pathway

Objective: to investigate the specific function of long non-coding rna hal in serous ovarian cancer (soc) and to further clarify the regulation of hal on emt pathway.Materials and methods: the expression of hal and twist1 was detected by q rt-pcr.Cck8 assay, wound healing assay, transwell assay and flow cytometry were used to detect the hal function on proliferation, migration, invasion and apoptosis in soc cells.Western blot was used to calculate protein level of vimentin, n-cadherin and e-cadherin.The effect of hal on tumorigenesis of soc was confirmed by xenograft nude mice model.Results: hal was significantly decreased in soc tissues and cells.Overexpression of hal inhibited the proliferation, migration and invasion of skov3 cells, but promoted apoptosis.Furthermore, overexpression of hal decreased the m rna and protein levels of twist1 via a binding between hal and twist1.Forced expression of twist1 reversed the inhibitory role of hal on soc cells’ migration and invasion.The in vivo tumor growth assay showed that hal suppressed soc tumorigenesis with inhibiting emt pathway.Conclusions: our research emphasized hal acting as a tumor-inhibiting gene by regulating emt signaling pathway, thus providing some novel experimental basis for clinical treatment of soc.

Journal: Bioscience Reports (2020)
Publication types: Research Article;
microRNA-613 exerts anti-angiogenic effect on nasopharyngeal carcinoma cells through inactivating the AKT signaling pathway by downregulating FN1

Background: nasopharyngeal carcinoma (npc) is a disease highly sensitive to radiotherapy with the unclear etiology.However, the specific effects of micro rna-613 (mi r-613) on npc still remain elusive.Therefore, the present study probes into the underlying mechanism of mi r-613 in npc via akt signaling pathway by regulating fibronectin 1 (fn1).Methods: first, microarray analysis was used to screen differentially expressed genes (degs) and regulatory mi rs associated with npc.Next, mi r-613 and fn1 expression in npc cells was determined, followed by verification of target relationship between mi r-613 and fn1.With npc cells exposed to mi r-613 mimic, si-fn1 and ly294002 (inhibitor of akt signaling pathway), the regulatory effects of mi r-613 on proliferation, apoptosis, invasion, migration and angiogenesis of npc cells were detected with ratio of b-cell lymphoma 2/bcl-2-associated x protein (bcl-2/bax), cleaved-caspase3, matrix metallopeptidase 2 (mmp-2), mmp-9, vascular endothelial growth factor (vegf), and cell adhesion molecule-1 (cd31) expression measured.Then, tumorigenesis and mvd were determined after xenograft in nude mice.Results: fn1 modulated by mi r-613 was critical for npc via the akt signaling pathway.Npc cells exhibited down-regulated mi r-613 and up-regulated fn1.Besides, mi r-613 was verified to target fn1.Moreover, overexpressed mi r-613, silenced fn1 or ly294002 treatment suppressed proliferation, invasion, migration, and angiogenesis in npc cells, which was indicated by reduced expression of akt, m tor, mmp-2, mmp-9, vegf, and cd31 as well as decreased ratio of bcl-2/bax and increased expression of cleaved-caspase3.Furthermore, cell apoptosis was promoted and tumorigenesis and mvd in nude mice were inhibited with overexpression of mi r-613, silenced fn1 or ly294002 treatment.Conclusion: taken together, mi r-613 inhibits angiogenesis in npc cells through inactivating fn1-dependent akt signaling pathway.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
RNAi-mediated TCF-3 gene silencing inhibits proliferation of Eca-109 esophageal cancer cells by inducing apoptosis

Esophageal cancer (ec) remains an important health problem in china.In the present study, through the use of si rna, specific gene knockdown of transcription factor 3 gene (tcf-3) was achieved in vitro and the effect of tcf-3 gene on human ec eca-109 cell proliferation and apoptosis.Eca-109 cells were treated using negative control (nc) of si rna against tcf-3 (si tcf-3) and si tcf-3 group.Colony formation assay was used to detect the colony formation ability in eca-109 cells.Mtt assay was used to measure the cell growth and viability, whereas br du assay was used to evaluate cell proliferation, and flow cytometry (fcm) to assess cell apoptosis.Reverse-transcription quantitative pcr (rt-q pcr) was applied to measure tcf-3 gene expression.Protein expressions of tcf-3, apoptosis-related proteins, bcl-2, bax, and caspase-3 were determined using western blotting.Transfection of si tcf-3 successfully down-regulated tcf-3 gene expression.In addition, si tcf-3, reduced eca-109 cell viability and proliferation, in a time-dependent manner, and inhibited progression of cell cycle from g0/g1 to s-stage.When treated with si tcf-3, the eca-109 cells exhibited increased apoptosis, with up-regulated cleaved caspase and bax expressions, whereas bcl-2 expression was down-regulated.The present study shows that tcf-3 gene silencing inhibits eca-109 cell growth and proliferation, suppresses cell cycle progression, and promotes apoptosis, which might serve as a new objective for ec treatment.

Journal: Bioscience Reports (2017)
Publication types: Research Article;
MicroRNA-98 Plays a Suppressive Role in Non-Small Cell Lung Cancer Through Inhibition of SALL4 Protein Expression

Micro rnas (mi rs) have been demonstrated to be significantly associated with the development and progression of non-small cell lung cancer (nsclc).However, the underlying mechanism of mi r-98 in mediating the malignant phenotypes of nsclc cells remains obscure.In this study, we found that mi r-98 was significantly downregulated in nsclc tissues compared to nontumor lung tissues.Downregulation of mi r-98 was significantly associated with poor differentiation and advanced clinical stage.Restoration of mi r-98 expression significantly decreased the proliferation, migration, and invasion of nsclc a549 and h1229 cells.Sall4 was identified as a target gene of mi r-98, and the protein expression of sall4 was negatively regulated by mi r-98 in nsclc a549 and h1229 cells.Overexpression of sall4 promoted a549 and h1229 cell proliferation, migration, and invasion and reversed the suppressive effects of mi r-98 on the malignant phenotypes of a549 and h1229 cells.Moreover, sall4 was found to be significantly upregulated in nsclc tissues compared to the nontumor lung tissues.We then observed an inverse correlation between the mi r-98 and sall4 levels in nsclc tissues.In vivo study revealed that mi r-98 overexpression suppressed nsclc growth.In summary, we demonstrate that mi r-98 acts as a tumor suppressor in nsclc cells by inhibiting the protein expression of its target gene sall4.Therefore, our study highlights the importance of the mi r-98/sall4 axis in nsclc.

Journal: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics (2016)
Publication types: Research Article;
Effects of LncRNA-HOST2 on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma cell line SMMC-7721

The present study explored the effect of long non-coding rna-human ovarian cancer-specific transcript 2 (lnc rna-host2) on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma (hcc) cell line smmc-7721.Hcc tissues and adjacent normal tissues from 162 hcc patients were collected.The hcc cell lines were assigned into the control group (regular culture), negative control (nc) group (transfected with si rna) and experimental group (transfected with lnc-host2 si rna).Quantitative real-time pcr (q rt-pcr) was used to detect the expression of lnc rna-host2.Cell proliferation was detected by cck-8 and colony-forming assays, cell apoptosis by flow cytometry and cell migration by scratch test.Transwell assay was used to evaluate cell migration and invasion abilities.Lnc rna-host2 expression in the hcc tissues increased 2–10 times than that in the adjacent normal tissues.Compared with the hl-7702 cell line, lnc rna-host2 expression in hep g2, smmc-7721 and huh7 cell lines was all up-regulated, but the smmc-7721 cell had the highest lnc-host2 expression.The lnc rna-host2 expression in the experimental group was down-regulated as compared with the control and nc groups.In comparison with the control and nc groups, cloned cells reduced, cell apoptosis increased, clone-forming ability weakened and inhibitory rate of colony formation increased in the experimental group.The cells migrating and penetrating into the transwell chamber were fewer in the experimental group than those in the control and nc groups.The experimental group exhibited slow wound healing and decreased cell migration area after 48 h.These findings indicate that lnc rna-host2 can promote cell proliferation, migration and invasion and inhibit cell apoptosis in human hcc cell line smmc-7721.

Journal: Bioscience Reports (2017)
Publication types: Research Article;
Long Noncoding RNA H19 Inhibits Cell Viability, Migration, and Invasion Via Downregulation of IRS-1 in Thyroid Cancer Cells

Thyroid cancer is a common endocrine gland malignancy which exhibited rapid increased incidence worldwide in recent decades.This study was aimed to investigate the role of long noncoding rna h19 in thyroid cancer.Long noncoding rna h19 was overexpressed or knockdown in thyroid cancer cells sw579 and tpc-1, and the expression of long noncoding rna h19 was detected by real-time polymerase chain reaction.The cell viability, migration, and invasion were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, transwell assay, and wound healing assay, respectively.Furthermore, cell apoptosis was analyzed by flow cytometry, and expressions of some factors that were related to phosphatidyl inositide 3-kinases/protein kinase b and nuclear factor κb signal pathway were measured by western blotting.This study revealed that cell viability and migration/invasion of sw579 and tpc-1 were significantly decreased by long noncoding rna h19 overexpression compared with the control group ( p &lt; .05), whereas cell apoptosis was statistically increased ( p &lt; .001).Meanwhile, cell viability and migration/invasion were significantly increased after long noncoding rna h19 knockdown ( p &lt; .05).Furthermore, long noncoding rna h19 negatively regulated the expression of insulin receptor substrate 1 and thus effect on cell proliferation and apoptosis.Insulin receptor substrate 1 regulated the activation of phosphatidyl inositide 3-kinases/akt and nuclear factor κb signal pathways.In conclusion, long noncoding rna h19 could suppress cell viability, migration, and invasion via downregulation of insulin receptor substrate 1 in sw579 and tpc-1 cells.These results suggested the important role of long noncoding rna h19 in thyroid cancer, and long noncoding rna h19 might be a potential target of thyroid cancer treatment.

Journal: Technology in Cancer Research & Treatment (2017)
Publication types: Research Article;
Effects of ebv-miR-BART7 on tumorigenicity, metastasis, and TRAIL sensitivity of non-small cell lung cancer

Objective to investigate how the epstein‐barr virus (ebv) encoded micro rna bart7 (mi r‐bart7) affects tumorigenicity, metastasis, and trail sensitivity of non‐small cell lung cancer (nsclc).Methods real time‐polymerase chain reaction was performed to detect mi r‐bart7 expression in nsclc cell lines.A549 and calu‐1 cells transfected with mi r‐bart7 inhibitors/mimics were used to do the in‐vitro experiments, including 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, annexin v‐fluorescein isothiocyanate/pi, wound‐healing, transwell, clonogenic assays, western blot analysis, and anchorage‐independent growth assay.Additionally, mice were used to inject a549 cells infected with mi r‐bart7 inhibitors to observe the tumorigenicity and metastasis of nsclc.Results trail‐resistant nsclc cell lines (h460r, a549, calu‐1, and h1299) exhibited higher mi r‐bart7 rather than sensitive h460 and h292 cells.After transfected with mi r‐bart7 inhibitors, we observed an inhibition in proliferation, migration, invasion, and colony formation, but an enhancement in apoptosis as well as expressions of caspase‐3 and caspase‐8 in a549 and calu‐1 cells.Besides, trail elevated the migration, invasion, and anchorage‐independent growth of a549 cells, which was reversed by silencing dr4 and dr5 (si drs).However, mi r‐bart7 inhibitors could reduce migration, invasion, and transformation potential of trail treated a549 cells.Moreover, the expression of transforming growth factor‐beta 1 (tgfβ1) could be decreased by mi r‐bart7 inhibitors with or without trail treatment.Moreover, the tumor growth, epithelial‐to‐mesenchymal transition, and metastasis was suppressed and tumor‐free survival was extended after injection of a549‐mi r‐bart7 inhibitors.Conclusion inhibition of mi r‐bart7 exerted inhibitory effects on cell proliferation, migration, invasion, and colony formation, consequently facilitating cell apoptosis and raising trail sensitivity, providing a new therapeutic target in nsclc.

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