syedzayyan/paper_mill_benchmark huggingface dataset:
Kaiso (ZBTB33) Downregulation by Mirna-181a Inhibits Cell Proliferation, Invasion, and the Epithelial-Mesenchymal Transition in Glioma Cells

Kaiso (zbtb33) expression is closely associated with the progression of many cancers and micro rna (mi rna) processing.Mi r-181a plays critical roles in multiple cancers; however, its precise mechanisms in glioma have not been well clarified.The goal of this study was to evaluate the interaction between kaiso and mi r-181a in glioma.Methods: quantitative real-time pcr (q rt-pcr) was performed to detect the levels of kaiso and mi r-181a in glioma tissues and cell lines.Cell proliferation, invasion, and the epithelial–mesenchymal transition (emt) were evaluated to analyze the biological functions of mi r-181a and kaiso in glioma cells.The m rna and protein levels of kaiso were measured by q rt-pcr and western blotting, respectively.Meanwhile, luciferase assays were performed to validate kaiso as a mi r-181a target in glioma cells.Results: we found that the level of mi r-181a was the lowest among mi r-181a–d in glioma tissues and cell lines, and the low level of mi r-181a was closely associated with the increased expression of kaiso in glioma tissues.Moreover, transfection of mi r-181a significantly inhibited the proliferation, invasion, and emt of glioma cells, whereas knockdown of mi r-181a had the opposite effect.Bioinformatics analysis predicted that kaiso was a potential target gene of mi r-181a, and the luciferase reporter assay demonstrated that mi r-181a could directly target kaiso.In addition, kaiso silencing had similar effects as mi r-181a overexpression in glioma cells, whereas overexpression of kaiso in glioma cells partially reversed the inhibitory effects of the mi r-181a mimic.Conclusionss: mi r-181a inhibited the proliferation, invasion, and emt of glioma cells by directly targeting and downregulating kaiso expression.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

Circular rnas (circ rnas) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (nsclc) tumorigenesis is not well understood.The aim of this study is to identify the expression level of circ pvt1 in nsclc and further investigated its functional relevance with nsclc progression both in vitro and in vivo.Methods: quantative real-time pcr was used for the measurement of circ pvt1 in nsclc specimens and cell lines.Fluorescence in situ hybridization analysis (fish) assay was used for the identification of sublocation of circ pvt1 in nsclc cells.Bioinformatics analysis, luciferase reporter assay and rna immunoprecipitation (rip) were performed to verify the binding of c-fos at circ pvt1 promoter region, and the direct interaction between circ pvt1 and mi r-125b.Gain- or loss-function assays were performed to evaluate the effects of circ pvt1 on cell proliferation and invasion.Western blot and immunohistochemistry assays were performed to detect the protein levels involved in e2f2 pathway.Results: we found that circ pvt1 was upregulated in nsclc specimens and cells.The transcription factor c-fos binded to the promoter region of circ pvt1, resulting in the overexpression of circ pvt1 in nsclc.Knockdown of circ pvt1 suppressed nsclc cell proliferation, migration and invasion, and increased apoptosis.In addition, circ pvt1 mediated nsclc progression via the regulation of e2f2 signaling pathway.More importantly, circ pvt1 was predominantly abundant in the cytoplasm of nsclc cells, and circ pvt1 could serve as a competing endogenous rna to regulate e2f2 expression and tumorigenesis in a mi r-125b-dependent manner, which is further verified by using an in vivo xenograft model.Conclusion: circ pvt1 promotes nsclc cell growth and invasion, and may serve as a promising therapeutic target for nsclc patients.Therefore, silence of circ pvt1 could be a future direction to develop a novel treatment strategy.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway

Objectives nasopharyngeal carcinoma (npc) is a type of nasopharyngeal disease with high metastasis and invasion properties.Tumor-associated alternative activated (m2) macrophages are evidenced to connect with npc.Based on this, this study purposes to explore the mechanism and participation of micro rna-18a (mi r-18a) from m2 macrophages in npc.Methods peripheral blood mononuclear cells were differentiated to macrophages and macrophages were polarized to m2 type by interleukin-4.Sune-1 and cne2 cells were transfected with restored or depleted mi r-18a or transforming growth factor-beta iii receptor (tgfbr3) to explore their roles in npc progression with the involvement of the tgf-β signaling pathway.Next, sune-1 and cne2 cells were co-cultured with m2 macrophages that had been treated with restored or depleted mi r-18a or tgfbr3 to comprehend their combined roles in npc with the involvement of the tgf-β signaling pathway.Results mi r-18a was highly expressed and tgfbr3 was lowly expressed in npc cells.Mi r-18a restoration, tgfbr3 knockdown or co-culture with mi r-18a mimics, or si-tgfbr3-transfected m2 macrophages promoted sune-1 cell progression, tumor growth in mice, decreased p-smad1/t-smad1, and elevated p-smad3/t-smad3.Mi r-18a downregulation, tgfbr3 overexpression, or co-culture with mi r-18a inhibitors or oe-tgfbr3-transfected m2 macrophages depressed cne2 cell progression, tumor growth in mice, increased p-smad1/t-smad1, and decreased p-smad3/t-smad3.Conclusion our study elucidates that mi r-18a from m2 macrophages results in promoted npc cell progression and tumor growth in nude mice via tgfbr3 repression, along with the smad1 inactivation and smad3 activation.

Journal: Discover Nano (formerly known as Nanoscale Research Letters) (2020)
Publication types: Research Article;
LINC00152 down-regulated miR-193a-3p to enhance MCL1 expression and promote gastric cancer cells proliferation

The present work aimed to probe into the effect of long non-coding rna (lnc rna) linc00152 on gastric cancer (gc) cells proliferation by regulating mi r-193a-3p and its target gene mcl1.Transfected si-linc00152 was used to down-regulate linc00152, and cells proliferation was measured by the cell counting kit-8 (cck-8) assay.Cell apoptosis and cell cycle were analyzed by flow cytometry (fcm).Besides, we also detected the potential functional effects of differential expression of linc00152 in vivo using nude mouse xenograft model.We overexpressed and downexpressed mi r-193a-3p to study the in vitro effect of mi r-193a-3p on gc cells proliferation and vitality.And mcl1 was silenced by sh rna to investigate the effect of mcl1 on proliferation of gc cells.In this research, linc00152 was proven to have a higher expression level in gc tissues than in the adjacent normal tissues.Gc cells proliferation was inhibited after linc00152 was down-regulated.Linc00152 inhibited the expression of mi r-193a-3p, which negatively regulated mcl1.In addition, gc cells proliferation was inhibited by cell transfection with sh rna-mcl1, and enhanced by transfection with mi r-193a-3p mimics.Our study suggested that linc00152 was overexpressed in gc tissues, and it down-regulated mi r-193a-3p to enhance mcl1 expression thereby promoting gc cells proliferation.

Journal: Bioscience Reports (2018)
Publication types: Research Article;
LncRNA FBXL19-AS1 promotes breast cancer cells proliferation and invasion via acting as a molecular sponge to miR-718

Long non-coding rnas (lnc rnas) have been suggested to serve vital roles in tumor initiation and progression.However, the expression and underlying mechanisms of lnc rna fbxl19-as1 in breast cancer (bc) remain unclear.In the present study, we found that fbxl19-as1 expression was significantly up-regulated and correlated with advanced clinical features and poor overall survival of bc patients.Functionally, fbxl19-as1 inhibition suppressed bc cells proliferation, invasion, and epithelial–mesenchymal transition (emt) processes in vitro and reduced tumor growth in vivo.In addition, we found that fbxl19-as1 might function as a ce rna to sponge mi r-718, and mi r-718 could rescue the effects of fbxl19-as1 on bc cells progression.Therefore, these findings suggested that fbxl19-as1 might serve as an oncogenic lnc rna and promoted bc progression by sponging mi r-718, indicating fbxl19-as1 could serve as a potential therapeutic target for bc treatment.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells

Background we elucidated the role of specific micro rnas (mi rnas) in the development of polycystic ovary syndrome (pcos) and explained the changes in the proliferation of granulosa cells.Excised ovarian cortex specimens were collected for mi rna profiling analysis ( n = 20 pcos females and 5 non-pcos females).Insulin-treated ovarian granulosa cells isolated from mice were used for mechanical studies.Results high mi r-140 expression was observed in pcos samples and insulin-treated granulosa cells compared to that in non-pcos and unstimulated cells, respectively.However, the ras-related protein rap-2a precursor (rap2a) was downregulated in in pcos.Mtt assay and ed u staining showed that an mi r-140 inhibitor attenuated viability in insulin-treated granulosa cells; cell viability increased with mi r-140 overexpression.Reduced expression of mi r-140 and the expression of the mi r-140 mimic resulted in marked cell apoptosis, as evidenced by the results of pi flow cytometry and annexin v-fitc; mi r-140 overexpression results in downregulated rap2a expression, and the mi r-140 mimic directly bound to the rap2a 3′-utr, causing increase in rap2a levels in insulin-treated granulosa cells; rna-mediated silencing of rap2a in insulin-treated granulosa cells restored cell proliferation and apoptosis to normal levels.Phosphorylated akt was found to be negatively regulated through cross-talk between mi r-140 and rap2a.Conclusions in conclusion, pcos ovarian cortex specimens and insulin-treated granulosa cells showed elevated expression of mi r-140, which could lead to increased proliferation and reduced apoptosis of cells by targeting rap2a.This study may pave the way for future research on the properties of granulosa cells in pcos.

Journal: Journal of Ovarian Research (2020)
Publication types: Research Article;
Long non-coding RNA SNHG1 protects human AC16 cardiomyocytes from doxorubicin toxicity by regulating miR-195/Bcl-2 axis

Doxorubicin (dox) is a highly effective anti-tumor drug, but its cardiotoxicity largely restricts its clinical application.The present study was designed to explore whether in vitro dox toxicity in ac16 cardiomyocytes can be regulated by long non-coding rna (lnc rna) small nucleolar rna host gene 1 (snhg1) and to elucidate the underlying mechanisms.We found that dox treatment led to severe damage in ac16 cells through decreasing cell viability and increasing cell apoptosis.Dox treatment also reduced the expression of snhg1 in ac16 cells, and overexpression of snhg1 alleviated the increased apoptosis in dox-treated ac16 cells.Moreover, we found that snhg1 could counteract the inhibitory effect of mi r-195 on bcl-2, and mi r-195 restoration blocked the beneficial effect of snhg1 against dox toxicity in ac16 cells.In short, the present study provided convincing evidence that snhg1 protects human ac16 cardiomyocytes from dox toxicity partly by regulating mi r-195/bcl-2 axis.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
MicroRNA-625 inhibits cell invasion and epithelial-mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma

Introduction: laryngeal squamous cell carcinoma (lscc) is a highly aggressive malignant cancer, but the molecular mechanisms underlying its development and progression remain largely elusive.The purpose of the present study is to investigate the expression profile and functional role of micro rna-625 (mi r-625) in lscc.Materials and methods: lscc tissues and adjacent normal tissues were collected from 86 lscc patients.The expression levels of mi r-625 and sox4 m rna in tissues and cells were detected by rt-q pcr analysis.The expression levels of sox4 and emt-related proteins were detected by western blot analysis.In vitro cell proliferation, migration, and invasion were detected by mtt assay, colony formation assay, wound healing assay, and transwell invasion assay, respectively.Dual-luciferase reporter assay was performed to verify the binding relationship between mi r-625 and the 3′-utr of sox4.Results: the results demonstrated that mi r-625 is significantly down-regulated in clinical lscc tissues, and its low expression may be closely associated with unfavorable clinicopathological characteristics of lscc patients.Overexpression of mi r-625 significantly suppressed the proliferation, migration, invasion, and emt of lscc cells.Furthermore, sox4 was validated as a direct target of mi r-625 in lscc cells, and rescue experiments suggested that restoration of sox4 blocked the tumor suppressive role of mi r-625 in lscc cells.Conclusions: taken together, these findings highlighted a critical role of mi r-625 in the pathogenesis of lscc, and restoration of mi r-625 could be considered as a potential therapeutic strategy against this fatal disease.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
FEZF1-AS1 is a key regulator of cell cycle, epithelial-mesenchymal transition and Wnt/β-catenin signaling in nasopharyngeal carcinoma cells

Background: accumulating studies discloses that long non-coding rnas (lnc rnas) serve important roles in human tumorigenesis, including nasopharyngeal carcinoma (npc).The purpose of the present study was to determine the role of lnc rna fezf1-as1 in npc.Materials and methods: the expression levels of fezf1-as1 in npc tissues and cell lines were detected by rt-q pcr analysis.Mtt assay was performed to investigate the proliferation of npc cells in vitro, whereas the migration and invasion of npc cells were determined by wound healing assay and transwell assay.A nude mouse tumor model was established to study the role of fezf1-as1 in npc tumorigenesis in vivo.The expression levels of proteins were detected by western blot assay.Results: the results showed that fezf1-as1 expression was increased in the npc tissues and cell lines, and the higher expression of fezf1-as1 was closely associated with poor prognosis of npc patients.We further observed that knockdown of fezf1-as1 inhibited the proliferation of npc cells in vitro and suppressed npc xenograft growth in vivo through inducing g2/m cell cycle arrest.The migratory and invasive abilities of npc cells were also reduced upon fezf1-as1 knockdown.Moreover, we demonstrated that inhibition of fezf1-as1 remarkably suppressed epithelial–mesenchymal transition (emt) and reduced β-catenin accumulation in nucleus in npc cells.Conclusions: collectively, we showed that fezf1-as1 might be a key regulator of cell cycle, emt and wnt/β-catenin signaling in npc cells, which may be helpful for understanding of pathogenesis of npc.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
Silencing of SOX12 by shRNA suppresses migration, invasion and proliferation of breast cancer cells

Sex determining region y-box protein 12 (sox12) is essential for embryonic development and cell-fate determination.The role of sox12 in tumorigenesis of breast cancer is not well-understood.Here, we found that sox12 m rna expression was up-regulated in human breast cancer tissues.To clarify the roles of sox12 in breast cancer, we used lentiviral sh rnas to suppress its expression in two breast cancer cells with relatively higher expression of sox12 (bt474 and mcf-7).Our findings strongly suggested that sox12 was critical for cell migration and invasion of breast cancer cells.We found that silencing of sox12 significantly decreased the m rna and protein levels of mmp9 and twist, while notably increased e-cadherin.Moreover, sox12 knockdown significantly inhibited the proliferation of breast cancer cells in vitro and the growth of xenograft tumours in vivo.Flow cytometry analysis revealed that breast cancer cells with sox12 knockdown showed cell cycle arrest and decreased m rna and protein levels of proliferating cell nuclear antigen (pcna), cdk2 and cyclin d1.Taken together, sox12 plays an important role in growth inhibition through cell-cycle arrest, as well as migration and invasion of breast cancer cells.

Journal: Bioscience Reports (2016)
Publication types: Research Article;
miR-517a is upregulated in glioma and promotes glioma tumorigenesis in vitro and in vivo

Mi r-517a has been reported to act as an oncogenic mi rna in human hepatocellular carcinoma and lung cancer.However, the roles and underlying molecular mechanism of mi r-517a in glioma remain unclear.In the present study, the expression of mi r-517a in clinical glioma tissues and glioma cell lines was examined by quantitative real-time pcr (q rt-pcr).Transfected with knockdown or forced expression of mi r-517a, the effects of mi r-517a on cell proliferation, migration, and invasion were detected through in vitro and in vivo tumorigenesis assays.Here, we report that mi r-517a expression was up-regulated in glioma tissues when compared with normal brain tissues, and up-regulation of mi r-517a level is tightly correlated with the status of pathology classification of glioma.A functional assay found that overexpression of mi r-517a in glioma cells markedly promoted or suppressed cell proliferation, colony formation, migration and invasion, respectively.Moreover, we revealed that the knockdown of mi r-517a dramatically suppressed glioma cell growth, migration, and invasion in vitro and in vivo.Furthermore, we found that knockdown of mi r-517a significantly induced apoptosis.Therefore, mi r–517a acts an oncogenic mi rna that promotes tumor progression in glioma, and thus may become a promising therapeutic candidate for glioma.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
Silencing CircHIPK3 sponges miR-93-5p to inhibit the activation of Rac1/PI3K/AKT pathway and improves myocardial infarction-induced cardiac dysfunction

The ce rna network involving circular rnas (circ rnas) is essential in the cardiovascular system.We investigated the underlying ce rna network involving circ hipk3 in myocardial infarction (mi).After an mi model was established, cardiac function was verified, and myocardial tissue damage in mice with mi was evaluated.A hypoxia model of cardiomyocytes was used to simulate mi in vivo , and the expression of and targeting relationships among circ hipk3, mi r-93-5p, and rac1 were verified.The apoptosis of cardiomyocyte was identified.Gain- and loss-of-functions were performed to verify the ce rna mechanism.The mi-modeled mice showed cardiac dysfunction and enlarged infarct size.Circ hipk3 was highly expressed in mouse and cell models of mi.Silencing circ hipk3 reduced infarct size, myocardial collagen deposition, and myocardial apoptosis rate and improved cardiac function.Circ hipk3 sponged mi r-93-5p, and mi r-93-5p targeted rac1.Overexpression of mi r-93-5p inhibited mi-induced cardiomyocyte injury and eliminated the harmful effect of circ hipk3.Circ hipk3 acted as ce rna to absorb mi r-93-5p, thus promoting the activation of the rac1/pi3k/akt pathway.We highlighted that silencing circ hipk3 can upregulate mi r-93-5p and then inhibit the activation of rac1/pi3k/akt pathway, which can improve mi-induced cardiac dysfunction.

Journal: Frontiers in Cardiovascular Medicine (2021)
Publication types: Research Article;
Long noncoding RNA FOXD2-AS1 promotes the malignancy of cervical cancer by sponging microRNA-760 and upregulating hepatoma-derived growth factor

Although the functions of long noncoding rna (lnc rna) called foxd2 adjacent opposite strand rna 1 ( foxd2-as1 ) have been well studied in multiple human cancer types, its expression status and detailed roles in cervical cancer remain unknown and merit investigation.This study was aimed at assessing foxd2-as1 expression in cervical cancer and at determining its effects on the aggressive behavior of cervical cancer in vitro and in vivo .Expression of foxd2-as1 in cervical cancer tissues and cell lines was determined via reverse-transcription quantitative pcr.The effects of foxd2-as1 on cervical cancer cells were examined by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide (mtt) assay, flow-cytometric analysis, migration and invasion assays, and an in vivo tumorigenicity assay.Foxd2-as1 was found to be significantly upregulated in cervical cancer tissues and cell lines.High foxd2-as1 expression was notably linked with the federation of gynecology and obstetrics (figo) stage, lymph node metastasis, and depth of cervical invasion in patients with cervical cancer.Kaplan–meier survival analysis revealed significantly shorter overall survival of patients when the tumor expression of foxd2-as1 was higher in comparison with those in patients with lower foxd2-as1 expression.In vitro functional assays revealed that downregulation of foxd2-as1 led to suppression of proliferation, migration, and invasiveness as well as to the induction of apoptosis of cervical cancer cells.In addition, foxd2-as1 silencing hindered tumor growth in vivo .Mechanism investigation revealed that foxd2-as1 functioned as a molecular sponge of micro rna-760 (mi r-760).Furthermore, hepatoma-derived growth factor ( hdgf ) was validated as a direct target gene of mi r-760 in cervical cancer cells.Moreover, an mi r-760 knockdown reversed the effects of foxd2-as1 silencing on cervical cancer cells.Foxd2-as1 possesses significant oncogenic activity in cervical cancer progression; this activity is mediated by sponging of mi r-760 with consequent upregulation of hdgf.The foxd2-as1 –mi r-760–hdgf axis might harbor promising targets for novel treatment strategies of cervical cancer.

Journal: Frontiers in Pharmacology (2020)
Publication types: Research Article;