syedzayyan/paper_mill_benchmark huggingface dataset:
Abnormally expressed JunB transactivated by IL-6/STAT3 signaling promotes uveal melanoma aggressiveness via epithelial-mesenchymal transition

Uveal melanoma (um) is the most common primary intraocular tumor in adults, and it carries a high risk of metastasis and mortality.Various proinflammatory cytokines have been found to be significantly increased in the aqueous humor or vitreous fluid of um patients; however, the role of these cytokines in um metastasis remains elusive.In the present study, we found that long-term interleukin (il)-6 exposure promoted the migration and invasion of um cells, diminished cell–cell adhesion, and enhanced focal adhesion.Moreover, il-6 treatment decreased the membranous epithelial marker tjp1 and increased the cytoplasmic mesenchymal marker vimentin.Further investigation demonstrated that jun b played a critical role in il-6-induced um epithelial–mesenchymal transition (emt).In um cells, the expression of jun b was significantly up-regulated during the il-6-driven emt process.Additionally, jun b induction occurred at the transcriptional level in a manner dependent on phosphorylated stat3, during which activated stat3 directly bound to the jun b promoter.Importantly, the knockdown of stat3 prevented the il-6-induced emt phenotype as well as cell migration and invasion, whereas jun b overexpression recovered the attenuated aggressiveness of um cells.Similarly, with il-6 stimulation, the stable overexpression of jun b strengthened the migratory and invasive capabilities of um cells and induced the emt-promoting factors (snail, twist1, matrix metalloproteinase (mmp)-2, mmp-14, and mmp-19).Analysis of the cancer genome atlas (tcga) database indicated that jun b was positively correlated with il-6 and stat3 in um tissues.The present study proposes an il-6/stat3/jun b axis leading to um aggressiveness by emt, which illustrates the negative side of inflammatory response in um metastasis.

Journal: Bioscience Reports (2018)
Publication types: Research Article;
Lentivirus-mediated angiopoietin-2 gene silencing decreases TNF-α induced apoptosis of alveolar epithelium cells

To investigate the role of angiopoietin-2 (ang-2) in tumor necrosis factor-α (tnf-α) induced apoptosis of alveolar epithelium cells (aecs).Methods: tnf-α was used to induce human alveolar epithelial hpaepi c cells, and ang-2 si rna vector was transfected to the hpaepi c cells.Rt–pcr and western blot were used.Tunel staining was applied to observe apoptosis, and annexin v–fitc–pi staining was used to calculate apoptosis rate.Results: m rna and protein expressions of ang-2, activated bax, and cleaved caspase-3 in hpaepi c cells were up-regulated, but the expression level of bcl-2 decreased (p &lt; 0.05).After transfection of ang-2 si rna, m rna and protein expressions of ang-2, activated bax, and cleaved caspase-3 in hpaepi c cells were down-regulated, but the expression level of bcl-2 increased (p &lt; 0.05).The number of apoptotic cells increased after tnf-α treatment; however, the number decreased after ang-2 si rna transfection.Annexin v–fitc–pi staining verified that the total number of apoptotic cells was elevated with tnf-α treatment, but declined after transfection of ang-2 si rna.Conclusions: the expression level of ang-2 increased during tnf-α-induced apoptosis.Inhibiting ang-2 expression may suppress the early stages of cell apoptosis and the degree of tnf-α-induced apoptosis.

Journal: Biochemistry and Cell Biology: Biochimie et Biologie Cellulaire (2016)
Publication types: Research Article;
TOX Acts an Oncological Role in Mycosis Fungoides

Mycosis fungoides (mf) is a low-grade lymphoma characterized by clonal expansion of atypical cd4+ skin-homing t lymphocytes.Herein, we examined the role of thymocytes selection associated hmg-box (tox), a gene previously found to be unregulated in mf skin biopsies, in mf pathogenesis.Tox encodes a high-mobility group family (hmg) domain dna binding nuclear protein, which regulates the differentiation of developing t-cells.First, we confirmed that tox expression levels in mf were increased compared with those in benign inflammatory dermatitis (bid) and normal skin.In addition, tox level increased with the progression mf from patch stage to tumor stage.Overexpression of tox accelerated the proliferation and migration of mf cell lines in vitro, which were blocked by akt inhibitors.In conclusion, our study confirmed that tox was highly expressed in mf lesions and accelerates the proliferation and migration of mf.Tox is a diagnostic marker for mf and may play a pathogenic role in disease progression.

Journal: PLoS One (2015)
Publication types: Research Article;
MicroRNA-769-5p suppresses cell growth and migration via targeting NUSAP1 in bladder cancer

Background nucleolar and spindle‐associated protein 1 (nusap1) has been identified to be strongly implicated in the carcinogenesis of cervical carcinoma, breast cancer, and liver cancer, and shows a high expression level in bladder cancer, indicating that nusap1 might be a potent target for cancer treatment.Using bioinformatics methods, we found that nusap1 was a putative target of mi r‐769‐5p.Here, we aimed to explore whether mi r‐769‐5p is involved in bladder cancer progression via targeting nusap1.Methods mi r‐769‐5p expression patterns in bladder cancer tissues and cells were detected by rt‐pcr.Kaplan‐meier was used to determine the clinical effects of mi r‐769‐5p expression levels on the overall survival of bladder cancer patients.Bioinformatics methods were used to predict the binding sites between mi r‐769‐5p and nusap1, which was verified by the luciferase gene reporter assay.Cck‐8, flow cytometry, wound healing and transwell chamber experiments were performed to test cell growth, apoptosis, migration and invasion capacities.Results mi r‐769‐5p was lowly expressed in bladder cancer tissues and cells, which was closely associated with poor prognosis.Overexpression of mi r‐769‐5p induced significant repressions in cell growth, migration, and invasion and caused an obvious increase in cell apoptosis, whereas these tendencies were reversed when nusap1 was upregulated.Conclusion this study demonstrates that mi r‐769‐5p functions as a tumor suppressor in bladder cancer via targeting nusap1.

Journal: Journal of Clinical Laboratory Analysis (2020)
Publication types: Research Article;
MiR-204 suppresses cell proliferation and promotes apoptosis in ovarian granulosa cells via targeting TPT1 in polycystic ovary syndrome

Micro rna (mi r)-204 is known to be associated with several different diseases.Polycystic ovary syndrome (pcos) has the highest incidence rate among the endocrine disorders in females between the ages of 18 and 44.We aimed to illustrate the mi r-204 function in pcos.Mi r-204 expression levels in tissue and cell were examined through rt-q pcr.Colony formation assay and mtt assay were applied to detect the cell viability.Flow cytometry was employed to examine the apoptosis and cell cycle in cells.Rna binding protein immunoprecipitation assay and luciferase reporter assay were provided to demonstrate the direct interaction between translationally controlled tumor protein (tpt1) and mi r-204.The expression of mi r-204 was declined in kgn cells and ovarian cortex tissues of pcos patients.Mi r-204 enhanced the colony formation capacity and cell proliferation in kgn cells.Cell cycle and apoptosis were also influenced by mi r-204.Since mi r-204 has direct interaction with tpt1, tpt1 overexpression suppressed the mi r-204-induced apoptosis and cell cycle alteration in kgn cells.Mi r-204 inhibits the cell viability and induces apoptosis and cell cycle arrest by directly interacting with tpt1, indicating a role of mi r-204 to be a potential target in the pcos patients.

Journal: Biochemistry and Cell Biology: Biochimie et Biologie Cellulaire (2019)
Publication types: Research Article;
MiR-301b promotes the proliferation, mobility, and epithelial-to-mesenchymal transition of bladder cancer cells by targeting EGR1

We investigated the role of mi r-301b in the modulation of the proliferation, migration, and invasion of bladder cancer (blca) cells.The expression of mi r-301b and egr1 (early growth response gene 1) m rna were analyzed by quantitative real-time polymerase chain reaction (q rt-pcr).A dual-luciferase reporter gene system was used to identify the target relationship between mi r-301b and egr1.Cell proliferation, cell cycle, and apoptosis were analyzed by mtt assay, colony-forming assay, and flow cytometry, respectively.Cell motility and invasiveness were assessed by wound healing and transwell assays.The expression of proteins involved in epithelial-to-mesenchymal transition (emt) and egr1 were determined by western blot.Our results showed that mi r-301b was up-regulated while egr1 was down-regulated in blca tissues compared with adjacent normal tissues.The proliferation, migration, and invasiveness of t24 cells (a kind of human blca cell) were suppressed by decreasing mi r-301b expression or increasing egr1 expression.In addition, mi r-301b promoted emt signaling by influencing the expression of related proteins.In conclusion, mi r-301b promotes the proliferation, migration, and aggressiveness of human blca cells by inhibiting the expression of egr1.

Journal: Biochemistry and Cell Biology: Biochimie et Biologie Cellulaire (2017)
Publication types: Research Article;
Inhibition of EZH2 enhances the therapeutic effect of 5-FU via PUMA upregulation in colorectal cancer

Although the survival rate of patients with cancer have increased due to the use of current chemotherapeutic agents, adverse effects of cancer therapy remain a concern.The reversal of drug resistance, reduction in harmful side effects and accelerated increase in efficiency have often been addressed in the development of combination therapeutics.Tazemetostat (epz-6438), a histone methyltransferase ezh2 selective inhibitor, was approved by the fda for the treatment of advanced epithelioid sarcoma.However, the effect of tazemetostat on colorectal cancer (crc) and 5-fu sensitivity remains unclear.In this study, the enhancement of tazemetostat on 5-fu sensitivity was examined in crc cells.Our findings demonstrated that tazemetostat combined with 5-fu exhibits synergistic antitumor function in vitro and in vivo in crc cells.In addition, tazemetostat promotes puma induction through the ros/er stress/chop axis.Puma depletion attenuates the antitumor effect of the combination therapy.Therefore, tazemetostat may be a novel treatment to improve the sensitivity of tumors to 5-fu in crc therapy.In conclusion, the combination of 5-fu and tazemetostat shows high therapeutic possibility with reduced unfavorable effects.

Journal: Cell Death & Disease (2020)
Publication types: Research Article;
Melatonin enhances TNF-α-mediated cervical cancer HeLa cells death via suppressing CaMKII/Parkin/mitophagy axis

Background tumor necrosis factor-α (tnf-α) immunotherapy controls the progression of human cervical cancer.Here, we explored the detailed molecular mechanisms played by melatonin in human cervical cancer (he la cells) death in the presence of tnf-α injury, with a particular attention to the mitochondrial homeostasis.Methods he la cells were incubated with tnfα and then cell death was determined via mtt assay, tunel staining, caspase elisa assay and western blotting.Mitochondrial function was detected via analyzing mitochondrial membrane potential using jc-1 staining, mitochondrial oxidative stress using flow cytometry and mitochondrial apoptosis using western blotting.Results our data exhibited that treatment with he la cells using melatonin in the presence of tnf-α further triggered cancer cell cellular death.Molecular investigation demonstrated that melatonin enhanced the caspase-9 mitochondrion death, repressed mitochondrial potential, increased ros production, augmented m ptp opening rate and elevated cyt-c expression in the nucleus.Moreover, melatonin application further suppressed mitochondrial atp generation via reducing the expression of mitochondrial respiratory complex.Mechanistically, melatonin augmented the response of he la cells to tnf-α-mediated cancer death via repressing mitophagy.Tnf-α treatment activated mitophagy via elevating parkin expression and excessive mitophagy blocked mitochondrial apoptosis, ultimately alleviating the lethal action of tnf-α on he la cell.However, melatonin supplementation could prevent tnf-α-mediated mitophagy activation via inhibiting parkin in a ca mkii-dependent manner.Interestingly, reactivation of ca mkii abolished the melatonin-mediated mitophagy arrest and he la cell death.Conclusions overall, our data highlight that melatonin enhances tnf-α-induced human cervical cancer he la cells mitochondrial apoptosis via inactivating the ca mkii/parkin/mitophagy axis.

Journal: Cancer Cell International (2019)
Publication types: Research Article;
Up-regulated microRNA-500a enhances hepatocarcinoma metastasis by repressing PTEN expression

It has been shown that mi r-500a may play an important role in the metastasis of hepatocarcinoma.The present study is to explore the influence of mi r-500a on hepatocarcinoma proliferation and metastasis, and the related molecular mechanism.The levels of mi r-500a in the serum and tissues of patients with metastatic or non-metastatic hepatocarcinoma or normal people were determined by quantitative reverse transcription-pcr (q rt-pcr).The proliferation, invasion, and cloning of hepatocarcinoma cell lines smmc-7721 after transfection with mimic mi r-500a or inhibitor mi r-500a were determined.Luciferase reported assay was used to explore the relationship between mi r-500a and phosphatase and tensin homologue (pten).Then, the protein expression of pten, p-akt (s473), p-akt (t308), akt, p-m tor, m tor, p-4e-bp1, 4e-bp1, p-s6k, and s6k in smmc-7721 cells were also determined by western blotting.The expression of mi r-500a in patients with metastatic hepatocarcinoma was significantly higher than the non-metastatic hepatocarcinoma.Overexpression of mi r-500a promoted the proliferation, invasion, and cloning of smmc-7721 cells.Luciferase reported assay showed mi r-500a could directly target at 3′-utr of pten.Overexpression of mi r-500a significantly reduced the expression of pten, and enhanced phosphorylation of akt, m tor, s6k, and 4e-bp1.In conclusion, the expression of mi r-500a was related to the proliferation and metastasis of hepatocarcinoma, which may be partly because of the activation of akt/m tor pathway through targetting pten.

Journal: Bioscience Reports (2017)
Publication types: Research Article;
Knockdown of TMEM14A expression by RNAi inhibits the proliferation and invasion of human ovarian cancer cells

Transmembrane protein 14a (tmem14a) is a member of tmems.Alterations in tmems expression have been identified in several types of cancer, but the expression and function of tmem14a in ovarian cancer is still unclear.Here, analysis on the expression data of the cancer genome atlas (tcga) ovarian serous cystadenocarcinoma (ov) dataset demonstrated the overexpression of tmem14a in ovarian cancer tissues compared with normal tissues, which was consistent with our real-time pcr analysis on ovarian cancer and normal tissues collected from 30 patients.In addition, tmem14a knockdown in two ovarian cancer cell lines, a2780 and ho-8910, reduced cell proliferation, causes cell cycle arrest and suppressed cell invasion.Moreover, silencing of tmem14a notably repressed g1/s cell cycle transition and cell invasion via down-regulating the expression of cell cycle related proteins (cyclin d1, cyclin e and pcna) and metastasis-related proteins (mmp-2 and mmp-9), respectively.Tmem14a knockdown significantly reduced the phosphorylation status of smad2 and smad3, downstream effectors of tgf-β signalling.In summary, these results indicate that tmem14a has a pro-tumorigenic effect in ovarian cancer cells, suggesting an important role of this protein in ovarian cancer oncogenesis and metastasis.

Journal: Bioscience Reports (2016)
Publication types: Research Article;
MicroRNA-34A inhibits the growth, invasion and metastasis of gastric cancer by targeting PDGFR and MET expression

Within the family of rtks (receptor tyrosine kinases), pdgfr (platelet-derived growth factor receptor) has been implicated in carcinogenesis and tumour development.Mi rnas (micro rnas), which can target the m rnas (messenger rnas) of cancer-associated genes, are abnormally expressed in various cancers.In this study, our aim was to identify the mi rnas that target pdgfr-α/β and to study the functions of these mi rnas.Mi r-34a was predicted to target pdgfr, and luciferase reporter assays showed that mi r-34a could directly target pdgfr.Meanwhile, we found that mi r-34a was down-regulated in gastric cancer tissues and was associated with metastasis.Our findings showed that mi r-34a could inhibit gastric cancer cell migration, invasion and proliferation, but these tumourigenic properties were only partially restored when pdgfr-α/β was overexpressed.In subsequent experiments, we found that the overexpression of both pdgfr and met could completely restore the gastric cancer tumourigenic properties.Moreover, the cancer-associated cell signalling pathway was studied, and we found that mi r-34a could inhibit akt [pkb (protein kinase b)] phosphorylation, which was restored by the overexpression of both pdgfr and met.In conclusion, mi r-34a may act as a potential tumour suppressor in gastric cancer and is associated with the mechanisms of gastric cancer metastasis; mi r-34a can inhibit gastric cancer tumourigenesis by targeting pdgfr and met through the pi3k (phosphoinositide 3-kinase)/akt pathway.

Journal: Bioscience Reports (2014)
Publication types: Research Article;
Large tumor suppressor kinase 2 overexpression attenuates 5-FU-resistance in colorectal cancer via activating the JNK-MIEF1-mitochondrial division pathway

Background 5-fluorouracil (5-fu) is a standard treatment for colorectal cancer, but most patients develop 5-fu resistance.Here, we conducted experiments to identify an effective approach to augment 5-fu-based treatment in colorectal cancer in vitro.Methods sw480 cells were in the present study and treated with 5-fu.Besides, lats2 adenovirus vectors were infected into sw480 cells.Western blotting, immunofluorescence and elisa were used to evaluate cell death and mitochondrial function.Pathway blocker was used to verify the role of mapk-jnk pathway in sw480 cell death.Results an obvious drop in large tumor suppressor kinase 2 (lats2) expression was observed in sw480 cells after treatment with 5-fu.In addition, upregulation of lats2 expression through infection with lats2 adenovirus further increased the reduction of sw480 cell viability induced by 5-fu.Functional exploration showed that 5-fu treatment suppressed mitochondrial membrane potential, enhanced cyt-c release into the nucleus, induced an oxidative injury environment by promoting ros production, and eventually upregulated bax-related mitochondrial apoptosis.Besides, lats2 overexpression in combination with 5-fu treatment further perturbed mitochondrial homeostasis, and this effect was achieved by elevating mitochondrial division.Mechanistically, lats2 overexpression and 5-fu co-treatment amplified mitochondrial division by upregulating mief1 expression in a manner dependent on mapk-jnk axis.Knockdown of mief1 using an si rna-mediated loss of function assay and/or inhibition of the mapk-jnk pathway using the specific inhibitor sp600125 abolished lats2/5-fu-mediated deleterious effects on mitochondrial performance and sw480 cell viability.Conclusions in light of the above findings, lats2 downregulation could be a potential mechanism of low response to 5-fu treatment.Overexpression of lats2 to further disrupt mitochondrial function via the jnk-mief1 signalling pathway might be a method to optimize 5-fu-based chemotherapy.

Journal: Cancer Cell International (2019)
Publication types: Research Article;
Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway

Background cancer cell viability is strongly modulated by the hippo pathway, which includes mammalian ste20-like protein kinase 1 (mst1) and yes-associated protein (yap).Although the roles of mst1 and yap in thyroid carcinoma cell death have been fully addressed, no study has determined whether differential modification of mst1 and yap could further suppress thyroid carcinoma progression.The aim of our study was to explore the antiapoptotic effects exerted by combined mst1 overexpression and yap knockdown in thyroid carcinoma mda-t32 cells in vitro.Methods mst1 adenovirus and yap sh rna were transfected into mda-t32 cells to overexpress mst1 and inhibit yap, respectively.Cell viability and death were determined via an mtt assay, a tunel assay and western blotting.Mitochondrial function, mitochondrial fission and pathway studies were performed via western blotting and immunofluorescence.Results the results of our study showed that combined mst1 overexpression and yap knockdown further augmented mda-t32 cell death by mediating mitochondrial damage.In addition, cancer cell migration and proliferation were suppressed by combined mst1 overexpression and yap knockdown.At the molecular level, mitochondrial membrane potential, atp production, respiratory function, and caspase-9-related apoptosis were activated by combined mst1 overexpression and yap knockdown.Further, we found that fatal mitochondrial fission was augmented by combined mst1 overexpression and yap knockdown in a manner dependent on the jnk-mief1 pathway.Inhibition of jnk-mief1 pathway activity abolished the proapoptotic effects exerted by mst1/yap on mda-t32 cells.Conclusions taken together, our data suggest that mst1 activation and yap inhibition coordinate to augment thyroid cancer cell death by controlling the jnk-mief1-mitochondria pathway, suggesting that differential regulation of the core hippo pathway components is potentially a novel therapeutic tool for the treatment of thyroid cancer.

Journal: Cancer Cell International (2019)
Publication types: Research Article;
Circular RNA circ-TSPAN4 promotes lung adenocarcinoma metastasis by upregulating ZEB1 via sponging miR-665

Background cancer metastasis is responsible for 90% of cancer‐related deaths.Recently, circular rna (circ rna) is deemed to be an important regulator of cancer progression.However, little is known about the role of circ rna in the metastasis of lung adenocarcinoma (luad).Herein, we investigated the clinical implication and regulatory effect of circ‐tspan4 (hsa_circ_0020732) in luad.Methods gene expression omnibus (geo) database ( gse104854 ) was used to identify the aberrantly expressed circ rnas in luad.The expression levels of circ‐tspan4, mi r‐4731‐5p, mi r‐665, and zeb1 were determined by quantitative reverse transcription pcr (q rt‐pcr).The functional experiments were carried out with wound healing and transwell assays.And, the luciferase reporter and rna pull‐down assays were employed to examine the crosstalk between circ‐tspan4, mi r‐665, and zeb1 .In vivo metastasis experiment was tested by the lung metastasis model.Results circ‐tspan4 was significantly upregulated in luad tissues and cell lines.The increased circ‐tspan4 was linked to advanced tumor‐node‐metastasis stage, lymph node and distant metastasis, and poor outcome.Lentivirus‐mediated stably circ‐tspan4 knockdown dramatically attenuated the metastatic ability of luad cells both in vitro and in vivo.Mechanistically, circ‐tspan4 directly interacted with mi r‐665, but not mi r‐4731‐5p, to increase the expression of zeb1 , which is a well‐known metastasis trigger.Importantly, the reduced metastatic capacity caused by circ‐tspan4 depletion was partially rescued by mi r‐665 silencing or zeb1 overexpression.Conclusions circ‐tspan4 plays a pivotal metastasis‐promoting role in luad through acting as a sponge for mi r‐665 and upregulating zeb1 .

Journal: Molecular Genetics & Genomic Medicine (2019)
Publication types: Research Article;