syedzayyan/paper_mill_benchmark huggingface dataset:
Emodin protects H9c2 cells against hypoxia-induced injury via regulation of miR-26a/survivin and the JAK1/STAT3 pathway

Background/aim congenital heart disease (chd) is a catastrophic disease.Emodin possesses biological properties in protecting against some diseases.Our study investigated to explore the effects of emodin on hypoxia‐stimulated cardiomyocytes, which mimicked chd in vitro.Methods h9c2 cells were stimulated with hypoxia and then the cells were treated with or without emodin, and/or transfected with mi r‐26a mimic, pc dna‐survivin and their corresponding negative control (nc).Cell viability and cell apoptosis were detected by cell counting kit‐8 assay and flow cytometry, respectively.In addition, the expression of apoptotic proteins, janus kinase 1 (jnk)/signal transducer and activator of transcription 3 (stat3) pathway factors, and survivin were evaluated by using western blot analysis.The expression of mi r‐26a was analyzed by quantitative real time polymerase chain reaction (q rt‐pcr).Moreover, the target of mi r‐26a was verified by using a luciferase report assay.Results hypoxia significantly decreased cell viability and increased cell apoptosis, and the accumulated levels of cleaved caspase‐3 and cleaved‐caspase‐9 were upregulated by hypoxia compared with the control.However, emodin administration led to the opposite result.A further result showed that emodin increased the phosphorylation of jnk/stat3 pathway–related proteins and the pathway inhibitor ag490 impaired the protective effects of emodin on hypoxia‐induced injury.In addition, emodin negatively regulated the mi r‐26a expression, and overexpression of mi r‐26a enhanced cell apoptosis and upregulated the expression of cleaved‐caspase‐3 and cleaved‐caspase‐9 compared with the nc.Moreover, emodin statistically upregulated the expression of survivin, and overexpression of mi r‐26a decreased the expression of survivin.The luciferase of mi r‐26a overexpression was decreased in the wild type of the survivin group.Conclusion emodin protects hypoxia‐induced cell injury as evidenced by increasing cell viability and decreasing apoptosis through downregulation of mi r‐26a as well as activation of the jnk/stat3 pathway.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;
Long noncoding RNA MEG3 inhibits proliferation and migration but induces autophagy by regulation of Sirt7 and PI3K/AKT/mTOR pathway in glioma cells

Glioma is a common primary brain tumor with high mortality rate and poor prognosis.Long noncoding rna maternally expressed gene 3 (meg3) is a tumor suppressor in diverse cancer types.However, the role of meg3 in glioma remains unclear.We aimed to explore the effects of meg3 on u251 cells as well as the underlying mechanisms.U251 cells were stably transfected with different recombined plasmids to overexpress or silence meg3.Effects of aberrantly expressed meg3 on cell viability, migration, apoptosis, expressions of apoptosis‐associated and autophagy‐associated proteins, and phosphorylated levels of key kinases in the pi3k/akt/m tor pathway were all evaluated.Then, messenger rna (m rna) and protein expression of sirt7 in cells abnormally expressing meg3 were estimated.In addition, effects of abnormally expressed meg3 and sirt7 on u251 cells were determined to reveal the underlying mechanism of meg3‐associated modulation.Cell viability and migration were significantly reduced by meg3 overexpression whereas cell apoptosis as well as bax and cleaved caspase‐3/‐9 proteins were obviously induced.Beclin‐1 and lc3‐ii/lc3‐i were upregulated and p62 was downregulated in meg3 overexpressed cells.In addition, the autophagy pharmacological inhibitor (3‐methyladenine, 3‐ma) affected the effect of meg3 overexpression on cell proliferation.Furthermore, the phosphorylated levels of key kinases in the pi3k/akt/m tor pathway were all reduced by meg3 overexpression.Sirt7 was positively regulated by meg3 expression, and effects of meg3 overexpression on u251 cells were ameliorated by sirt7 silence.Meg3 suppressed cell proliferation and migration but promoted autophagy in u251 cells through positively regulating sirt7, involving in the inhibition of the pi3k/akt/m tor pathway.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
MicroRNA-105 promotes epithelial-mesenchymal transition of nonsmall lung cancer cells through upregulating Mcl-1

Background a growing number of micro rnas have been proved to play significant roles in limiting tumor growth and the epithelial‐mesenchymal transition (emt) process of nonsmall cell lung cancer (nsclc).Present work aims to study the function of micro rna (mi r)‐105 in emt of nsclc cells, which is unrevealed yet.Methods two nsclc cell lines a549 and calu‐3 were transfected with mi r‐105 mimic, inhibitor, or scrambled control.And then the effects of mi r‐105 were evaluated by performing trypan blue staining, transwell assay, annexin‐fitc/propidium iodide (pi) double staining and western blot analysis.The expression levels of myeloid cell leukemia‐1 (mcl‐1) after transfection were tested by real‐time quantitative polymerase chain reaction and western blot analysis.Whether mcl‐1 was a downstream effector of mi r‐105, and the involvement of mammalian target of rapamycin (m tor) and p38 mitogen‐activated protein kinase (p38mapk) signaling pathways were assessed.Results the overexpression of mi r‐105 significantly increased the viability and migration of a549 and calu‐3, but had no impacts on cell apoptosis.Meanwhile, e‐cadherin was remarkably downregulated, and n‐cadherin, vimentin, zeb1, and snail were upregulated by mi r‐105 overexpression.Mcl‐1 was positively regulated by mi r‐105, and the effects of mi r‐105 overexpression on a549 and calu‐3 cells viability, migration and emt were all flattened by mcl‐1 silence.Both m tor and p38mapk pathways were activated in mi r‐105‐overexpressing and mcl‐1‐overexpressing cells.Besides, inhibition of m tor and p38mapk pathways by using rapamycin and vx‐702 abolished the regulatory effects of mcl‐1 on emt.Conclusion our study underlines the importance of mi r‐105 in modulating nsclc cells emt.Mi r‐105 promoted the emt of nsclc cells possibly via upregulation of mcl‐1 and thereby activation of m tor and p38mapk signaling.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Long noncoding RNA TALNEC2 plays an oncogenic role in breast cancer by binding to EZH2 to target p57KIP2 and involving in p-p38 MAPK and NF-κB pathways

We aimed to investigate the potential role and regulatory mechanism of long noncoding rna tumor‐associated lnc rna expressed in chromosome 2 (talnec2) in breast cancer.The expression of talnec2 in breast cancer tissues and cells were investigated.Mcf‐7 and mda‐mb‐231 cells were transfected with small interfering rna (si rna) duplexes for targeting talnec2 (si‐talnec2), enhancer of zeste homolog 2 (ezh2; si‐ezh2) and p57 kip2 (si‐p57 kip2 ), and their corresponding controls (si‐nc).The viability, colony forming ability, cell cycle, apoptosis, and autophagy of transfected cells were assessed.The expressions of p‐p38 mitogen‐activated protein kinase (mapk) and nuclear factor κb (nf‐κb) pathway‐related proteins were investigated.The results showed that talnec2 was highly expressed in breast cancer tissues and cells.Knockdown of talnec2 significantly inhibited the malignant behaviors of mcf‐7 and mda‐mb‐231 cells, including inhibiting cell viability and colony forming, arresting cell cycle at g0/g1 phase, inducing cell apoptosis, and promoting cell autophagy.Ezh2 was a talnec2 binding protein, which was upregulated in breast cancer tissues and cells and could negatively regulate p57 kip2 .Effects of talnec2 knockdown on malignant behaviors of mcf‐7 cells were reversed by p57 kip2 knockdown.The expressions of p‐p38, rel a, and rel b in mcf‐7 cells were decreased after knockdown of talnec2 or ezh2, which were reversed by knockdown of p57 kip2 concurrently.In conclusion, talnec2 may play an oncogenic role in breast cancer by binding to ezh2 to target p57 kip2 .Activation of p‐p38 mapk and nf‐κb pathways may be key mechanisms mediating the oncogenic role of talnec2 in breast cancer.Talnec2 may serve as a promising target in the therapy of breast cancer.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Long noncoding RNA HAGLROS regulates apoptosis and autophagy in colorectal cancer cells via sponging miR-100 to target ATG5 expression

The aim of this study was to explore the relationship between the expression of hoxd antisense growth‐associated long noncoding rna (haglros) and prognosis of patients with colorectal cancer (crc), as well as the roles and regulatory mechanism of haglros in crc development.The haglros expression in crc tissues and cells was detected.The correlation between haglros expression and survival time of crc patients was investigated.Moreover, haglros was overexpressed and suppressed in hct‐116 cells, followed by detection of cell viability, apoptosis, and the expression of apoptosis‐related proteins and autophagy markers.Furthermore, the association between haglros and mi r‐100 and the potential targets of mi r‐100 were investigated.Besides, the regulatory relationship between haglros and pi3k/akt/m tor pathway was elucidated.The results showed that haglros was highly expressed in crc tissues and cells.Highly expression of haglros correlated with a shorter survival time of crc patients.Moreover, knockdown of haglros in hct‐116 cells induced apoptosis by increasing the expression of bax/bcl‐2 ratio, cleaved‐caspase‐3, and cleaved‐caspase‐9, and inhibited autophagy by decreasing the expression of lc3ii/lc3i and beclin‐1 and increasing p62 expression.Furthermore, haglros negatively regulated the expression of mi r‐100, and haglros controlled hct‐116 cell apoptosis and autophagy through negatively regulation of mi r‐100.Autophagy related 5 (atg5) was verified as a functional target of mi r‐100 and mi r‐100 regulated hct‐116 cell apoptosis and autophagy through targeting atg5.Besides, haglros overexpression activated phosphatidylinositol‐3‐kinase/protein kinase b/mammalian target of rapamycin (pi3k/akt/m tor) pathway.In conclusion, a highly expression of haglros correlated with shorter survival time of crc patients.Downregulation of haglros may induce apoptosis and inhibit autophagy in crc cells by regulation of mi r‐100/atg5 axis and pi3k/akt/m tor pathway.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Knockdown of long noncoding RNA GAS5 attenuates H2O2-induced damage in retinal ganglion cells through upregulating miR-124: Potential role in traumatic brain injury

Background optic nerve injury is one of the most common and serious complications in traumatic brain injury (tbi).Alleviating degree of optic nerve injury is important to cure of tbi.This study explored the role of long noncoding rna (lnc rna) gas5 in mice retinal ganglion cells (rgcs) suffered to h 2 o 2 injury.Methods primary rgc (prgcs) were treated with h 2 o 2 to simulate an in vitro oxidation stress model.Lnc rna gas5 and mi r‐124 expressions were knocked down by cell transfection with short‐hairpin rna against gas5 and mi r‐124 inhibitor, and the transfection efficiency was determined by q rt‐pcr.Cell viability, apoptotic cell rate, and production of reactive oxygen species (ros) was analyzed by cck‐8 assay, pi/fitc‐annexin v method, and dcfh‐da fluorometric assay.Cell apoptosis‐associated proteins as well as activations of jak/stat3 signaling and jnk signaling were analyzed by western blot.Results h 2 o 2 treatment‐induced cell injury was inhibited by lnc rna gas5 silence.Specifically, knockdown of gas5 improved viability of primary prgcs, inhibited apoptosis, decreased ros expression, increased antiapoptosis proteins’ expressions, and decreased proapoptosis proteins’ expressions.It was also found that mi r‐124 inhibitor treatment impaired the cell protective effect of gas5 silence, indicating low level of gas5 protected prgcs via upregulating mi r‐124.Gas5 silence might exert cytoprotection effect via activating jak/stat3 signaling pathway and inhibiting activation of jnk signaling pathway.Conclusion knocking down lnc rna gas5 alleviated h 2 o 2 ‐induced injury in prgcs via upregulation of mi r‐124, which might dependent on activation of jak/stat3 signaling pathway and inhibition of jnk signaling pathway.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Long noncoding RNA SNHG16 contributes to the development of bladder cancer via regulating miR-98/STAT3/Wnt/β-catenin pathway axis

This study aimed to investigate the role and the possible mechanism of the long noncoding small nucleolar rna host gene 16 (snhg16) in bladder cancer development.The expression of snhg16 in the tumor tissues and plasma of patients with bladder cancer as well as bladder cancer cell lines was detected.T24 cells were then transfected with sh‐snhg16 to further investigate the effects of suppression of snhg16 on t24 cell proliferation, apoptosis, migration, and invasion.In addition, the regulatory relationships between snhg16 and mi r‐98 as well as the target of mi r‐98 were explored.Besides, the association between snhg16 and the wnt/β‐catenin pathway was further elucidated.The snhg16 expression was upregulated in the tumor tissues and plasma of patients with bladder cancer, as well as bladder cancer cells.Suppression of snhg16 inhibited t24 cell proliferation, promoted apoptosis, and suppressed migration and invasion in vitro.In addition, snhg16 negatively regulated mi r‐98 expression and regulated the malignant behaviors of t24 cells through sponging mi r‐98.Moreover, signal transducer and activator of transcription 3 (stat3) was identified as a functional target of mi r‐98, and mi r‐98 regulated the malignant behaviors of bladder cancer cells by targeting stat3.Besides, suppression of snhg16 inhibited the activation of the wnt/β‐catenin pathway, which was further regulated by mi r‐98 and stat3, indicating that the effects of snhg16/mi r‐98/stat3 on t24 cells were achieved through the wnt/β‐catenin pathway.Our findings reveal that long noncoding rnas snhg16 is upregulated in bladder cancer and contributes to the development of bladder cancer possibly via regulating the mi r‐98/stat3/wnt/β‐catenin pathway axis.The snhg16/mi r‐98/stat3/wnt/β‐catenin pathway axis may provide a new strategy for bladder cancer treatment.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Ras-ERK1/2 signaling contributes to the development of colorectal cancer via regulating H3K9ac

Backgrounds/aims ras is a control switch of erk1/2 pathway, and hyperactivation of ras-erk1/2 signaling appears frequently in human cancers.However, the molecular regulation following by ras-erk1/2 activation is still unclear.This work aimed to reveal whether ras-erk1/2 promoted the development of colorectal cancer via regulating h3k9ac.Methods a vector for expression of k-ras mutated at g12 v and t35s was transfected into sw48 cells, and the acetylation of h3k9 was measured by western blot analysis.Mtt assay, colony formation assay, transwell assay, chromatin immunoprecipitation and rt-q pcr were performed to detect whether h3k9ac was contributed to k-ras-mediated cell growth and migration.Furthermore, whether hdac2 and pcaf involved in modification of h3k9ac following ras-erk1/2 activation were studied.Results k-ras mutated at g12 v and t35s induced a significant activation of erk1/2 signaling and a significant down-regulation of h3k9ac.Recovering h3k9 acetylation by using a mimicked h3k9ac expression vector attenuated the promoting effects of ras-erk1/2 on tumor cells growth and migration.Besides, h3k9ac can be deacetylated by hdac2 and mdm2-depedent degradation of pcaf.Conclusion h3k9ac was a specific target for ras-erk1/2 signaling pathway.H3k9 acetylation can be modulated by hdac2 and mdm2-depedent degradation of pcaf.The revealed regulation provides a better understanding of ras-erk1/2 signaling in tumorigenesis.

Journal: BMC Cancer (2018)
Publication types: Research Article;
MicroRNA-103 confers the resistance to long-treatment of adriamycin to human leukemia cells by regulation of COP1

Adriamycin (adr) is an anti‐cancer drug which offers improvement in survival for acute myeloid leukemia (aml) patients.However, the drug resistance is almost inevitable.Increasing evidences suggested that micro rnas (mi rnas) were associated with cancer chemo‐resistance.Here, we aimed to explore the possible mechanism of mi r‐103 affected resistance to adr in aml cells.Different concentrations of adr were used to induce k562 and kasumi‐1 cells, and mi r‐103 mimic, inhibitor were transfected into k562 and kasumi‐1 cells.Cell viability and proliferation were determined by trypan blue staining and mtt assays for evaluating k562 and kasumi‐1 cells drug resistance.The relationship of mi r‐103 and cop1, trib1, and c/ebpα were analyzed by q rt‐pcr and western blot.Cell proliferation, viability were detected again.Besides, the expressions of main factors of cell cycle and pi3k/akt signal pathway were analyzed by western blot.Results showed that adr inhibited cell viability and proliferation in k562 and kasumi‐1 cells.However, k562 and kasumi‐1 cells appeared drug resistance for 50 passages at 0.8 μm of adr.In addition, mi r‐103 expression was up‐regulated in adr‐resistant k562 cells (k562/adr) and overexpression of mi r‐103 increased k562 cells drug resistance via promoting cell viability and cell cycle‐related factors expressions.Cop1 was positively regulated by mi r‐103, suppression of mi r‐103 recovered k562/adr cells drug resistance by regulation of cop1, trib1, and c/ebpα.Besides, mi r‐103 blocked pi3k/akt signal pathway by regulation of cop1.These data indicated that mi r‐103 was up‐regulated in drug resistant cells and it may regulate adr‐resistance by regulation of cop1 in aml cells.

Journal: Journal of Cellular Biochemistry (2017)
Publication types: Research Article;
Baicalein retards proliferation and collagen deposition by activating p38MAPK-JNK via microRNA-29

Immoderate proliferation and deposition of collagen generally result in hypertrophic scars and even keloids.Micro rna‐29 (mi r‐29) has been proved as a crucial regulator in these pathological processes.Although mounting evidence have proved baicalein (bai) impairs scar formation, it is still incompletely understood whether mi r‐29 participated in the underlying mechanism.In the present study, nih‐3t3 cells were stimulated with bai, and then cell viability was analyzed by cell counting kit‐8 (cck‐8) and western blot.We further analyzed total soluble collagen, collagen 1, and alpha‐smooth muscle actin (α‐sma) in nih‐3t3 cells, which were exposed to transforming growth factor beta 1 (tgf‐β1)/bai, using a sircol assay kit, quantitative reverse transcription‐pcr (q rt‐pcr) and western blot, respectively.Besides, the mi r‐29 inhibitor was transduced and its transfection efficiency was verified by q rt‐pcr.Finally, the phosphorylated p38 mitogen‐activated protein kinase (p38mapk) and c‐jun n‐terminal kinase (jnk) were examined by western blot.Bai effectively retarded nih‐3t3 proliferation in a dose‐dependent manner.Besides, tgf‐β1‐induced deposition of total soluble collagen and synthesis of collagen 1 and α‐sma were repressed by bai at m rna and protein levels.However, mi r‐29 inhibitor reversed the effects of bai.Remarkably, bai promoted phosphorylated expression of p38mapk and jnk while mi r‐29 inhibitor reversed its effects on the phosphorylated expression of p38mapk and jnk.Bai effectively weakened the cell viability and repressed tgf‐β1‐induced total soluble collagen as well as collagen 1 and α‐sma by upregulating mi r‐29.Mechanically, bai activates the p38mapk/jnk pathway by promoting mi r‐29.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;
Knockdown of long noncoding RNA urothelial carcinoma-associated 1 inhibits cell viability, migration, and invasion by regulating microRNA-182 in gastric carcinoma

Background long noncoding rna urothelial carcinoma–associated 1 (uca1) has been reported to be a vital mediator in various cancers.But, in terms of gastric cancer (gc), the effects of uca1 on gc cell proliferation, migration, invasion, and apoptosis remain unclear.This study aimed to uncover the potential regulatory mechanism of uca1 in gc cells.Methods the expression level of uca1 was first examined in the five different cell lines of hek293, ccl‐153, huvec, sun‐216, and sgc‐7901 using a reverse‐transcriptase quantitative polymerase chain reaction.Then, the vectors of short hairpin uca1, the micro rna‐182 (mi r‐182) mimic/inhibitor, and the p ex‐tissue inhibitor of metalloproteinases 2 (timp2)/small interfering timp2 were transfected into sun‐216 and sgc‐7901 cells to alter uca1, mi r‐182, and timp2 expression.To investigate the biological functions, cell viability, migration, invasion, and apoptosis were examined by cell counting kit‐8, transwell, and flow cytometry.The key factors of apoptosis and phosphoinositide 3‐kinase (pi3k)/protein kinase b (akt)/glycogen synthase kinase 3β (gsk3β) and nuclear factor κb (nf‐κb) signal pathways were determined by western blot analysis.Results uca1 was upregulated in sun‐216 and sgc‐7901 cells than in the other three cell lines of hek293, ccl‐153, and huvec.Knockdown of uca1 significantly suppressed cell viability, migration, and invasion, and promoted apoptosis by regulating b‐cell lymphoma 2, bax, and cleaved‐caspase‐3/9 expressions.However, mi r‐182 overexpression markedly reversed the regulatory effect of uca1 knockdown on sun‐216 and sgc‐7901 cells.Timp2 was a direct target gene of mi r‐182, and timp2 overexpression exhibited the same effect of uca1 knockdown on cell viability, migration, invasion, and apoptosis.Besides, mi r‐182 activated pi3k/akt/gsk3β and nf‐κb signal pathways by regulation of timp2.Conclusion knockdown of uca1 exerts an anticancer effect on gc cells by regulating mi r‐182.

Journal: Journal of Cellular Biochemistry (2018)
Publication types: Research Article;
Knockdown of long non‐coding RNA ANRIL inhibits proliferation, migration, and invasion but promotes apoptosis of human glioma cells by upregulation of miR‐34a

Gliomas are the most common types of primary central nervous system malignancy found in adults.Long non‐coding rna antisense non‐coding rna in the ink4 locus (anril) variants are associated with glioma and mi r‐34a is markedly downregulated in u251 glioma cells.The 3′‐untranslated region (3′utr) of silent information regulator 1 (sirt1) contains a conserved site that is targeted directly by mi r‐34a.Therefore, in this study, we investigated the roles of anril, mi r‐34a, and sirt1 in glioma and their potential interactions.Firstly, expression of anril in normal glia cells and five glioma cell lines was measured.Then, effects of anril suppression on cell proliferation, apoptosis, migration and invasion of u251 cells as well as expression of mi r‐34a were assessed.Meanwhile, effects of mi r‐34a on u251 cells silencing anril were tested.Whether sirt1 is a target of mi r‐34a was verified, followed by estimating the role of sirt1 overexpression in u251 cells overexpressing mi r‐34a.Finally, the involved signaling pathways were assessed.Anril was upregulated in glioma cells and its suppression inhibited cell proliferation, migration and invasion but promoted cell apoptosis.Anril acted as a sponge of mi r‐34a, and sirt1 is a target of mi r‐34a.Then, sirt1 was proved to function through activation of the pi3k/akt and m tor signaling pathways.In conclusion, anril was upregulated in glioma, and its inhibition could repress cell proliferation, migration and invasion but inhibit cell apoptosis through mi r‐34a‐mediated downregulation of sirt1, involving the inactivation of the pi3k/akt and m tor pathways.

Journal: Journal of Cellular Biochemistry (2017)
Publication types: Research Article;