syedzayyan/paper_mill_benchmark huggingface dataset:
Overexpressed microRNA-539-5p inhibits inflammatory response of neurons to impede the progression of cerebral ischemic injury by histone deacetylase 1

Several micro rnas (mi rnas or mi rs) regulate cerebral ischemic injury outcomes; however, little is known about the role of mi r-539-5p during cerebral ischemic injury or the postischemic state.Cerebral ischemic injury was modeled in vitro by exposing human cortical neurons to oxygen-glucose deprivation (ogd) and in vivo by occluding the middle cerebral artery (mcao) in a rat model.The effects of mi r-539-5p, histone deacetylase 1 (hdac1), and early growth response 2 (egr2) on cerebral ischemia were investigated using gain- and loss-of-function experiments.We identified changes in mi r-539-5p, hdac1, egr2, and phosphorylated c-jun nh 2 -terminal kinase (jnk).The interaction among mi r-539-5p, hdac1, and egr2 was determined by dual luciferase reporter gene assay, chromatin immunoprecipitation, and coimmunoprecipitation.We also investigated the effects on cell viability and apoptosis and changes in inflammatory cytokine expression and spatial memory on mcao rats.Mi r-539-5p and egr2 were poorly expressed, while hdac1 was highly expressed in ogd-treated hcn-2 cells.Mi r-539-5p targeted hdac1, while hdac1 prevented acetylation of egr2 resulting in its downregulation and subsequent activation of the jnk pathway.Overexpression of mi r-539-5p or egr2 or silencing hdac1 improved viability and reduced apoptosis of ogd-treated hcn-2 cells in vitro.Furthermore, overexpression of mi r-539-5p improved spatial memory, while decreasing cell apoptosis and inflammation in mcao rats.Collectively, these data suggest that mi r-539-5p targets hdac1 to upregulate egr2, thus blocking the jnk signaling pathway, by which cerebral ischemic injury is alleviated.

Journal: American Journal of Physiology - Cell Physiology (2020)
Publication types: Research Article;
Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

An increasing body of evidence shows that long noncoding rnas (lnc rnas) are involved in many different cancers.In this study, we aimed to investigate the competing endogenous rna (ce rna)-dependent mechanism by which the lnc rna gas5 contributes to the development of breast cancer.Methods: a total of 68 breast cancer patients were enrolled, and breast cancer and adjacent normal tissues were collected.The human breast cancer cell lines mda-mb-231, mda-mb-453, bt549, sk-br-3 and mcf-7 and human breast cell line mcf10a were utilized in this study.Quantitative reverse transcription-polymerase chain reaction (q rt-pcr) and western blotting were performed to detect expression of relative factors.Rna immunoprecipitation (rip) was used to evaluate the relationship between gas5 and mi r-23a, and a dual luciferase reporter gene assay was employed to assess the relationship between atg3 and mi r-23a.A subcutaneous xenograft nude mouse model was generated to examine the role of gas5 and its regulatory pathway in autophagy.Results: gas5 levels were frequently decreased in breast cancer tissues and cell lines, and its relatively low expression was closely related to a larger tumour size, advanced tumour-node-metastasis (tnm) stage and estrogen receptor-negative (er-) breast cancer tissues.More importantly, we found that gas5 promoted autophagy, with enhanced autophagosome formation after gas5 overexpression.Gas5 was found to act as a micro rna sponge in a pathway that included mi r-23a and its target gene atg3.The gas5-mi r-23a-atg3 axis significantly regulated autophagy in vivo and in vitro.Conclusions: in summary, we report that the gas5-mi r-23a-atg3 axis can be regarded as a key regulator of autophagy pathways in breast cancer; it may constitute a promising biomarker and therapeutic target in the future.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
MicroRNA-34a Inhibition of the TLR Signaling Pathway Via CXCL10 Suppresses Breast Cancer Cell Invasion and Migration

Breast cancer (bc) starts as a local disease, but it can metastasize to the lymph nodes and distant organs.However, the metastatic process is still poorly understood.The m rna microarray datasets gse26910 and gse33447 show that cxcl10 is up-regulated in bc, and the micro rna microarray dataset gse38167 and a network meta-analysis of micro rna expression profile studies in human bc suggest that micro rna-34a (mi r-34a) is down-regulated in bc.Cxcl10 was predicted as a target of mi r-34a by micro rna.org.In this study, we uncovered a cxcl10-independent mechanism by which mi r-34a exerts its antimetastatic activity in bc.Methods: to investigate the clinical significance of mi r-34a in bc, we collected cancer tissues and paracancerous tissues from 258 patients with bc.In addition, a series of inhibitors, mimics, and si rnas was introduced into mcf-7 and t47d cells to validate the regulatory mechanisms by which mi r-34a regulates cxcl10.Next, to better understand the pivotal role of tlr signaling pathway inhibition in mcf-7 and t47d cells, we blocked the tlr signaling pathway using ox papc, an antagonist of tlr signaling.Results: among bc patients, mi r-34a was down-regulated, cxcl10 was up-regulated, and the tlr signaling pathway was activated.Determination of luciferase activity revealed that cxcl10 was a target of mi r-34a.Through gain- and loss-of-function studies, mi r-34a was demonstrated to negatively regulate cxcl10; inhibit activation of the tlr signaling pathway; significantly suppress in vitro cell proliferation, migration, and invasion; and induce apoptosis.Conclusion: our findings suggest that functional loss or suppression of the tumor suppressor cxcl10 due to induction of mi r-34a leads to inhibition of the tlr signaling pathway during breast tumorigenesis, providing a novel target for the molecular treatment of breast malignancies.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

This study aims to investigate the effects of cdkn2a (p16ink4a/p14arf) over-expression on the proliferation and migration of human melanoma a375 cells.Methods: melanoma tissues and pigmented nevi tissues were collected.Human melanoma a375 cells were transfected by cdkn2a (p16ink4a) and cdkn2a (p14arf) over-expressing vectors and then assigned into blank, negative control (nc), p16ink4a and p14arf groups.The expression of cdkn2a (p16ink4a) and cdkn2a (p14arf) m rna and protein was detected by q rt-pcr and western blotting.Cck-8, flow cytometry and transwell assays were applied to observe cell proliferation, the cell cycle and apoptosis, and migration and invasion, respectively.The model of subcutaneous xenografts in nude mice was established to measure cell growth in vivo.Results: compared with pigmented nevi tissues, cdkn2a (p16ink4a) and cdkn2a (p14arf) m rna and protein expression were significantly decreased in melanoma tissues.Cdkn2a (p16ink4a) and cdkn2a (p14arf) over-expression inhibited proliferation, migration, invasion and progression from g0/g1 to s phase of a375 cells and xenograft tumor growth, but promoted apoptosis.Conclusion: our study demonstrated that over-expression of cdkn2a (p16ink4a) and cdkn2a (p14arf) suppressed proliferation and migration of human melanoma a375 cells.

Journal: Cellular Physiology and Biochemistry (2016)
Publication types: Research Article;
Baicalin relieves TNF-α-evoked injury in human aortic endothelial cells by up-regulation of miR-145

Hypertension is recognized to be associated with low‐grade inflammation.Baicalin (bai) is reported to possess various pharmacological including anti‐inflammatory activities.This research explored the molecular mechanism by which bai functions in human aortic endothelial cells (haecs).Haecs were pretreated with bai.Cell viability, apoptosis, and expressions of crucial proteins were respectively evaluated using cell counting kit‐8 assay, flow cytometry, and western blot.Productions of cytokines were respectively assessed employing quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay.Cell transfection was utilized to alter mi r‐145 expression.The expressions of proteins participated in jnk and p38mapk pathways were analyzed utilizing western blot.Tnf‐α inducement successfully evoked inflammatory injury in haecs, exhibiting as prominently suppressed viability, while facilitated apoptosis and productions of cytokines.However, bai pretreatment significantly ameliorated tnf‐α‐triggered inflammatory injuries.Besides, mi r‐145 expression was markedly inhibited by tnf‐α inducement, while notably elevated by bai pretreatment.Although mi r‐145 overexpression had no significant influence on apoptosis, mi r‐145 silence observably reversed bai pretreatment‐evoked protective influences on tnf‐α‐induced haecs, as well as the inhibited impacts on the levels of key proteins involved in jnk and p38mapk pathways.This investigation illustrated that bai relieved tnf‐α‐triggered injuries through upregulating mi r‐145 via suppressing jnk and p38mapk pathways.

Journal: Phytotherapy Research (PTR) (2019)
Publication types: Research Article;
Physcion Synergistically Enhances the Cytotoxicity of Sorafenib in Hepatocellular Carcinoma

Hepatocellular carcinoma (hcc) is a common human malignancy.Physcion is a naturally occurring anthraquinone derivative found in plant and marine sources.Our previous studies have indicated that physcion could suppress tumor growth and induce apoptosis in hcc.This study was aimed to investigate the effect of a combination of physcion and sorafenib on hcc.Our findings indicated that physcion could significantly augment the antiproliferative and proapoptotic activities of sorafenib in vitro and in vivo .Mechanistically, the synergistic effect correlates with physcion‐induced suppression of notch3/akt signaling.This preclinical evidence highlights the potential application of physcion in the treatment of hcc.Anat rec, 302:2171–2177, 2019.© 2019 american association for anatomy

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2019)
Publication types: Research Article;
Amentoflavone Promotes Apoptosis in Non-Small-Cell Lung Cancer by Modulating Cancerous Inhibitor of PP2A

Non‐small‐cell lung cancer (nsclc) is one of the most common human malignancies.Amentoflavone (af) is one of bioflavonoid compounds isolated from selaginella tamariscina spring.This study was designed to examine the effect of af on nsclc.Our results indicated that af decreased cell viability of both h1299 and h358 cells.Colony formation assay also showed that af was able to suppress the anchorage‐independent growth of nsclc cells.Af also triggered cell cycle arrest by downregulating cyclin d1, cdk4, and cdk6.The pro‐apoptotic activity of af was confirmed by hoechst staining and flow cytometry.The effect of af on activation of caspase‐3, upregulation of bax, and downregulation of bcl‐2 was examined by western blot.The anti‐growth and pro‐apoptotic activities of af were further validated in xenograft murine model.I traq assay showed that cancerous inhibitor of pp2a (cip2a) expression was markedly downregulated by af treatment in h1299 cells.In addition, q rt‐pcr and western blot also showed that af was able to dose‐dependently inhibit cip2a expression.Meanwhile, the activity of protein phosphatase 2a (pp2a) was enhanced by af treatment.The m rna and protein expression of cip2a as well as pp2a activity in xenograft tumor tissue were examined, which indicated that the in vivo anticancer activity of af was associated with downregulation of cip2a and reactivation of pp2a.Moreover, our results showed that the anti‐growth and pro‐apoptotic activities of af were augmented by cip2a knockdown and attenuated by ectopic cip2a expression.Our results indicated that af exhibited anticancer activity in nsclc by targeting cip2a.Anat rec, 302:2201–2210, 2019.© 2019 american association for anatomy

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2019)
Publication types: Research Article;
MiR‐141‐3p Suppresses Tumor Growth and Metastasis in Papillary Thyroid Cancer via Targeting Yin Yang 1

Micro r‐141‐3p has been found to be downregulated in papillary thyroid carcinoma (ptc), while little is known about the cellular functions and precise signals elicited by mi r‐141‐3p in ptc.The results of this study indicated that the expression of mi r‐141‐3p was aberrantly down‐regulated in ptc tissues and cell lines, compared with the adjacent normal tissues and normal thyroid epithelial cells.Furthermore, the mi r‐141‐3p expression level was negatively associated with tnm stage and lymph node metastasis in ptc.Expression of mi r‐141‐3p effectively inhibited cell growth, promoted apoptosis, and suppressed invasion in ptc cells.Meanwhile, mi r‐141‐3p knockdown with mi r‐141‐3p inhibitor reversed these effects.Consistent with the in vitro study, mi r‐141‐3p also exhibited anti‐neoplastic activity in vivo .Moreover, the results revealed that mi r‐141‐3p directly recognized the 3′ untranslated region (3′utr) of yin yang 1 (yy1) and negatively regulated the expression of yy1 at both protein and m rna levels.Ectopic expression of yy1 could effectively abrogate the anti‐metastatic and proapoptotic effects of mi r‐141‐3p.In summary, the findings suggested that mi r‐141‐3p can act as a tumor suppressor in ptc and may be a potential therapeutic target for ptc treatment.Anat rec, 302:258–268, 2019.© 2018 wiley periodicals, inc.

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2018)
Publication types: Research Article;
Role of EAST-6 in renal injury by regulating microRNA-155 expression via TLR4/MyD88 signaling pathway in mice with Mycobacterium tuberculosis infection

The study aims to investigate the underlying mechanism involved in the early secretory antigenic target-6 (esat-6) in renal injury through regulation of the expression of mi r-155 through the oll-like receptor (tlr)-4 (tlr4)/myeloid differentiation factor 88 (my d88) signaling pathway in mycobacterium tuberculosis (mtb)-infected mice.Sixty c57bl/6 mice with mtb-induced renal injury were randomly assigned into control, mtb, mimic, inhibitor, inhibitor + esat6, and inhibitor + esat6 + tak242 groups.Body weight, the ratio of kidney weight to body weight (kw/bw), blood urea nitrogen (bun), and serum creatinine (scr) of mice were measured.Flow cytometry was used to detect renal activation in mice.Expressions of mi r-155 and esat6 were detected by quantitative real-time pcr (q rt-pcr), and western blotting was used to examine the expressions of esat6, tlr4, and my d88.Expressions of tumor necrosis factor-α (tnf-α), interleukin-17 (il-17), and interferon-γ (ifn-γ) were measured by q rt-pcr and elisa.Compared with the control group, the bun and scr levels as well as the expression levels of mi r-155, tlr4, my d88, tnf-α, il-17, and ifn-γ increased, while kw/bw decreased in the mtb and mimic groups.In comparison with the mtb group, the above indexes except kw/bw were elevated in the mimic group, but were reduced in the inhibitor group, while the kw/bw dropped in the mimic group but increased in the inhibitor group.Compared with the inhibitor group, the kw/bw decreased while the rest of the indexes increased in the inhibitor + esat6 group.Esat6 may induce renal injury by promoting mi r-155 expression through the tlr-4/my d88 signaling pathway in mtb-infected mice.

Journal: Bioscience Reports (2017)
Publication types: Research Article;
Upregulation of microRNA-340 promotes osteosarcoma cell apoptosis while suppressing proliferation, migration and invasion by inactivating the CTNNB1-mediated Notch signaling pathway

Osteosarcoma (os) is the most common histological form of primary bone cancer.It is most prevalent in teenagers and young adults.The present study aims at exploring the regulatory effect of micro rna-340 (mi r-340) on os cell proliferation, invasion, migration, and apoptosis via regulating the notch signaling pathway by targeting β-catenin (cadherin-associated protein) 1 (ctnnb1).Os tissues belonging to 45 patients and normal femoral head tissues of 45 amputees were selected.Cells were allocated to different groups.In situ hybridization was performed to determine the positive rate of mi r-340 expression while immunohistochemistry was used to determine that of ctnnb1 and b-cell lymphoma 2 (bcl-2).We used a series of experiments to measure the expressions of related factors and assess rates of cell proliferation, migration, invasion, cycle, and apoptosis respectively.Our results show that mi r-340 was expressed a higher level in normal tissue than os tissue.Expression of notch, ctnnb1, hairy and enhancer of split 1 (hes1), bcl-2, runt-related transcription factor 2 (runx2), and osteocalcin increased and that of mi r-340, bcl-2 interacting mediator of cell death (bim), and bcl-2 associated protein x (bax) decreased in os tissues.U-2os cell line had the highest mi r-340 expression.We also found that the up-regulation of mi r-340 had increased expression of mi r-340, bim, and bax but decreased expression of notch, ctnnb1, hes1, bcl-2, runx2, and osteocalcin.Up-regulation of mi r-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion.Our study demonstrates that overexpression of mi r-340 could suppress os cell proliferation, migration, and invasion as well as promoting os cell apoptosis by inactivating the notch signaling pathway via down-regulating ctnnb1.Functional mi r-340 overexpression might be a future therapeutic strategy for os.

Journal: Bioscience Reports (2018)
Publication types: Research Article;
MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2

Lung cancer is one of the most common causes of cancer related deaths worldwide.The role of several micro rnas (mi rnas) including mi r-196b in different cancers has already been established.The study was aimed to explore the role of mi r-196b in lung cancer and its possible underlying mechanism.Methods: human lung cancer cell line a549 was transfected with mi r-196b mimic, mi r-196b inhibitor and corresponding controls.Then cell viability, migration, invasion, and apoptosis of a549 lung cancer cells either with overexpression or with suppression of mi r-196b were estimated sequentially.Next, dual luciferase activity assay was performed to clarify whether runx2 was a direct target of mi r-196b.Finally, the expressions of main factors associated with epithelial mesenchymal transition (emt), pi3k/akt/gsk3β, smad, and jnk pathways were detected by western blot.Results: mi r-196b expression was significantly decreased in a549, h1650 and h1299 cell lines compared with in wi-38 and hel-1 cell lines.Overexpression of mi r-196b suppressed cell viability, migration, invasion, and induced apoptosis as well as inhibited tgf-β induced emt process in a549 cells.In addition, runx2 was a putative target of mi r-196b, and runx2 silence remarkably increased cell apoptosis and abolished the promotive effects of mi r-196b suppression on cell viability, migration and invasion.Finally, mi r-196b also mediated its action by inactivation of pi3k/akt/gsk3β, smad, and jnk pathways by down-regulation of runx2.Conclusion: mi r-196b functions as a tumor suppressor that inhibited cell growth and metastasis of lung cancer cells by targeting runx2.These findings provided further evidences for treatment of lung cancer.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Long Non-Coding RNA ROR1-AS1 Induces Tumorigenesis of Colorectal Cancer by Affecting Wnt/β-catenin Signaling Pathway

Recent studies have discovered that long noncoding rnas (lnc rnas) play an important role in malignant tumors.In this research, lnc rna ror1-as1 was selected to identify how it affects the development of colorectal cancer (crc).Ror1-as1 expression was detected by rt-q pcr in crc tissue samples.Ror1-as1 expression level and patients’ overall survival time were analyzed.Functional experiments were conducted to identify the changes of biological behaviors in crc cells after knockdown of ror1-as1.Moreover, we also explored the underlying mechanism.Detection of ror1-as1 expression level in patients’ tissues showed that ror1-as1 was higher in crc tissues than that in adjacent ones.Ror1-as1 expression was negatively associated with patients’ overall survival time.Cell growth ability was inhibited due to knockdown of ror1-as1 in vitro.Moreover, cell migration and invasion were repressed after ror1-as1 knockdown.Furthermore, due to knockdown of ror1-as1, the targeted proteins in wnt/β-catenin signaling pathway were suppressed.These results suggest that ror1-as1 could enhance cell metastasis and proliferation via inducing wnt/β-catenin signaling pathway, which might offer a potential therapeutic target in crc.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
Overexpression of miR‐4286 is an unfavorable prognostic marker in individuals with non–small cell lung cancer

Non–small cell lung cancer (nsclc) is still an unresolved source of tumor‐related death internationally.Current studies have discovered that micro rnas (mi rnas) are associated with diverse cancers development, including nsclc.Our paper focused on the functional character of mi r‐4286 in nsclc.Mi r‐4286 level in 68 cases of nsclc tissues, matched neighboring nontumor tissues and different cancer cell lines were inspected by quantitative reverse transcription polymerase chain reaction (q rt‐pcr).The connection concerning mi r‐4286 expression and clinicopathological features of patients with nsclc were further determined.After knockdown or overexpression of mi r‐4286, cell viability, cell cycle, and/or apoptotic cells were examined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (mtt) and flow cytometry assay, respectively.Moreover, the cell cycle‐ and apoptosis‐related proteins were estimated by q rt‐pcr and western blot.In comparison with the matched nontumor tissues, mi r‐4286 was significantly enhanced in lung malignancy tissues and different cell lines.Mi r‐4286 expression was related with the tumor‐node‐metastasis stage, lymphatic metastasis, and distant metastasis.Cell viability was ominously weakened by suppression of mi r‐4286 in a549 cells, whereas was statistically upregulated by overexpression of mi r‐4286 in nci‐h1299 cells.Additionally, we detected that suppression of mi r‐4286 tempted cell cycle arrest in g1 stage and fortified apoptosis in a549 cells.Runx3 was recognized as one target gene of mi r‐4286, and the impacts of suppression of mi r‐4286 on cell viability and apoptosis were through regulation of runt‐related transcription factor 3.Our study suggests that mi r‐4286 overexpression represents a tumor promoter role in nsclc cells.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;