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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

LncRNA COL1A2-AS1 inhibits the scar fibroblasts proliferation via regulating miR-21/Smad7 pathway

Highlights: • LncRNA COL1A2-AS1 is upregulated in hypertrophic scar tissue and fibroblasts. • LncRNA COL1A2-AS1 suppresses fibroblasts proliferation by promoting Smad7 expression. • miR-21 is involved in lncRNA COL1A2-AS1-induced expression of Smad7. • Overexpression of miR-21 attenuates COL1A2-AS1–mediated proliferation suppression of hypertrophic scar fibroblasts. lncRNA COL1A2-AS1 (COL1A2 antisense RNA 1), a lncRNA overexpressed in hypertrophic scar, has been demonstrated to be involved in the hypertrophic scar formation. However, the mechanisms of lncRNA COL1A2-AS1 inhibiting the scar fibroblasts proliferation remains not well understood. In this study, we demonstrated that lncRNA COL1A2-AS1 was upregulated in hypertrophic scar tissue and fibroblasts, and suppressed fibroblasts proliferation by promoting Smad7 expression. Furthermore, we found that miR-21 was involved in lncRNA COL1A2-AS1-induced expression of Smad7, by which COL1A2-AS1 acted as endogenous sponge to adsorb miR-21 and in turn regulated Smad7 and a cascade of molecular to play a protective role in hypertrophic scar. In addition, overexpression of miR-21 attenuated COL1A2-AS1-mediated proliferation suppression of hypertrophic scar fibroblasts. In conclusion, our study demonstrated that COL1A2-AS1/miR-21/Smad pathway plays an important role in inhibiting hypertrophic scar formation, and suggested this novel pathway may be a new target for hypertrophic scar treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

GLP-1 receptor agonist liraglutide exerts central action to induce β-cell proliferation through medulla to vagal pathway in mice

Highlights: • ICV injected GLP-1RA liraglutide and GLP-1 induce pancreatic β-cell proliferation. • This effect is induced by single shot liraglutide at low dose not touching feeding. • This effect is inhibited by atropine and hence possibly mediated by vagal efferent. • ICV liraglutide activates dorsal vagal complex (DVC), suggesting DVC-vagal reflex. • This pathway may serve to counteract β-cell reduction in diabetic patients. Endogenous GLP-1 and GLP-1 receptor agonists (GLP-1RAs) regulate glucose metabolism via common and distinct mechanisms. Postprandial release of GLP-1 is modest and it is degraded by DPP-4 within 2 min, and hence it cannot enter the brain in substantial amount. In contrast, DPP-4-resistant GLP-1RAs are administered at 10 times higher concentration than endogenous GLP-1 level, which enables them to reach several brain regions including ARC and AP, the areas implicated in glucose metabolism. Hence, some of the effects of GLP-1RAs observed clinically and experimentally, including pancreatic β-cell proliferation, are thought to involve the brain. However, the effects of centrally acting GLP-1/GLP-1RAs on glucose metabolism and underlying neural mechanism are unclear. This study aimed to establish the link of central GLP-1/GLP-1RA action to pancreatic β-cell proliferation. Both subcutaneous (SC) and intracerebroventricular (ICV) injections of liraglutide increased the number of pancreatic β-cells expressing Ki67 and PCNA, proliferation markers, in C57BL/6J mice. This effect was induced by single ICV administration of liraglutide at relatively low dose that was incapable of suppressing food intake. These SC and ICV liraglutide-induced effects were inhibited by 50% and 70%, respectively, by pretreatment with atropine, a muscarinic receptor blocker. ICV liraglutide induced c-Fos expression in the area postrema (AP), nucleus tractus solitaries (NTS), and dorsal motor nucleus of the vagus (DMX) of the brain stem. These results demonstrate that central action of liraglutide induces pancreatic β-cell proliferation via the pathway involving the brain stem AP/NTS/DMX area and vagus nerve. This route is highly sensitive to GLP-1/GLP-1RA. Hence, this brain-pancreatic β-cell pathway may operate in type 2 diabetic patients treated with GLP-RAs and serve to counteract the reduction of β-cell mass.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Myotube-derived factor promotes oligodendrocyte precursor cell proliferation

Highlights: • Myotube-derived factors promote proliferation of oligodendrocyte precursor cells (OPCs). • Myotube-derived factors do not promote OPC migration and differentiation. • Candidate genes which promote OPC proliferation were identified by RNA sequence analysis. • Molecules released by myotubes may be involved in OPC proliferation. Muscle cells secrete numerous molecules that function as endocrine hormones and regulate the functions of distant organs. Myelination in the central nervous system (CNS) is regulated by peripheral hormones. However, the effects of muscle-derived molecules on myelination have not been sufficiently analyzed. In this study, we show that muscle-releasing factors promote proliferation of oligodendrocyte precursor cells (OPCs), which is an element of myelination process. Supernatants of mouse myotube cultures stimulated bromodeoxyuridine (BrdU) incorporation into mouse OPCs. Mouse myotube supernatants did not enhance mouse OPC transmigration and myelin basic protein (MBP) expression. RNA sequencing identified candidate genes with hormonal functions that were expressed in mouse myotubes. These data support the possibility that hormonal molecules secreted by myotubes contribute to OPC proliferation and myelination.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Biomechanical strain-induced modulation of proliferation coincides with an ERK1/2-independent nuclear YAP localization

Highlights: • Strain-induced modulation of nuclear YAP amount coincides with proliferation. • YAP-inhibiting drug Verteporfin yields distinct reduction of KI-67-positive cells. • This demonstrates regulatory involvement of nuclear YAP in proliferation. • Strain-induced YAP modulation is mechanistically independent from ERK1/2 activity. • ERK1/2 activity influences total YAP amount, exclusively in strained cells. Biomechanical strain induces activation of the transcriptional co-activator yes-associated protein (YAP) by nuclear re-distribution. Recent findings indicate that the mechanically responsive mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 1/2 is involved in the amount of nuclear YAP, reflecting its activation. In this context, we conducted experiments to detect how biomechanical strain acts on the subcellular localization of YAP in periodontal cells. To this end, cells were subjected to 2.5% static equiaxial strain for different time periods. Western blot and fluorescence imaging-based analyses revealed a clear modulation of nuclear YAP localization. This modulation fairly coincided with the altered course of the KI-67 protein amount in conjunction with the percentage of KI-67-positive and thus proliferating cells. The inhibition of the ERK1/2 activity via U0126 yielded an unchanged strain-related modulation of nuclear YAP localization, while YAP amount in whole cell extracts of strained cells was decreased. Administration of the YAP-inhibiting drug Verteporfin evoked a clear reduction of KI-67-positive and thus proliferating cells by approximately 65%, irrespective of strain. Our data reveal YAP as a regulator of strain-modulated proliferation which occurs in a MAPK-independent fashion.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Learning Global Proliferation Expertise Evolution Using AI-Driven Analytics and Public Information

Detecting and anticipating global proliferation expertise and capability evolution from unstructured, noisy, and incomplete public data streams is a highly desired, but extremely challenging task. Here, in this article, we present our pioneering data-driven approach to support the non-proliferation mission to detect and explain the evolution of proliferation expertise and capability development globally from terabytes of publicly available information (PAI), focusing on our knowledge extraction pipeline and descriptive analytics. We first discuss how we fuse nine open-source data streams, including multilingual data, to convert 4 TB of unstructured data to structured knowledge and encode dynamically evolving proliferation expertise representations—content and context graphs. For this, we rely on natural language processing (NLP) and deep learning (DL) models to perform information extraction, topic modeling, and distributed text representation (aka embedding) learning. We then present interactive, usable, and explainable descriptive analytics to refine domain knowledge and present it in a human-understandable form. Finally, we introduce future work avenues that will leverage our dynamic knowledge representations and descriptive analytics to enable predictive and prescriptive inferences to achieve real-time domain understanding and contextual reasoning about global proliferation expertise and capability evolution.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗
NASA NTRS2024

Impact of Simulated Microgravity on Mesenchymal Stem Cell Proliferation

Background Long term exposure to microgravity has adverse effects on human body such as bone loss. Due to the vital role of mesenchymal stem cell (MSC) in bone regeneration, studying MSC under microgravity conditions has been of interest during the past decade. However, high cost and limited access to space flight can dampen enthusiasm of researchers. Microgravity simulators provide a way to investigate the effects of microgravity in human physiology. Methods In this study, we compared MSC cultures under simulated microgravity using random positioning machine (RPM) and Gravite 3D simulators. Two culture durations, 1 week and 2 weeks, were selected for MSC cultures without media change. To evaluate impact of simulated microgravity on cell proliferation, cell counting was performed using trypan blue exclusion assay. Additionally, RNA samples and conditioned media were collected for further analysis. Results After 1 week and 2 weeks, no cell morphology change was observed from RPM and Gravite cultures compared to control. Notably, distinct lower cell confluence at the edge of the flasks on the RPM was observed, which could be caused by fluid sheer forces. MSCs cultured on both microgravity simulators showed decreased cell proliferation after 1-week culture. After 2-week culture, cells grown on the RPM showed no significant difference in cell proliferation compared with control while cells cultured on the Gravite bioreactor showed significantly enhanced MSC proliferation. Conclusion Type of microgravity simulator and duration of culture significantly affect MSC proliferation. Further investigation into how simulated microgravity influences MSC gene expression and cytokine secretion related to bone loss is currently on going in our lab.

Cuiping Zhang↗
DOE OSTI2019

Development and Examination of a Proliferation Trade Risk Metric

A Proliferation Trade Risk metric has been calculated for each country represented in a publicly-available trade dataset. This metric, comprising both direct and indirect proliferation trade risk components, represents the risk that each country’s proliferation-relevant exports will go to a designated set of proliferation threat countries. This metric can serve to prioritize nonproliferation export control capacity building engagement. Further, within such engagement, the decomposition of the proliferation trade risk metric can identify specific industrial sectors and trade relationships of greatest importance for outreach and enforcement measures. Finally, these supply-side perspectives can be complemented by threat-based profiles identifying the most important suppliers to each threat country.

export control, trade analysis↗
DOE OSTI2016

Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation

Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RARα fusion protein. We have previously found that PML-RARα-regulated miR-125b is highly expressed in APL; however, the characteristics of the regulatory effects and mechanisms of miR-125b involved in APL proliferation have yet to be clarified. In this study, we demonstrate that miR-125b promotes the proliferation of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways. Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets of miR-125b, which we verified using luciferase reporter constructs. Moreover, we demonstrate that the expression of miR-125b targets is downregulated in leukemic cells in patients with APL. Thus, our results provide evidence that miR-125b can modulate multiple oncogenic cell proliferation pathways and may be a novel therapeutic target for APL. - Highlights: • miR-125b promotes cell proliferation by AKT and MAPK signaling pathways. • miR-125b target to MAP3K11,BTG2, RPS6KA1 and PRDM1. • MAP3K11,BTG2, RPS6KA1 and PRDM1 were dowregulated by miR-125b in NB4 and primary cells from APL patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Rock2 promotes RCC proliferation by decreasing SCARA5 expression through β-catenin/TCF4 signaling

Rho-associated coiled-coil forming protein kinase 2 (Rock2), as a key effector of the small GTPase RhoA, is involved in tumor development. Scavenger receptor class A member 5 (SCARA5) is an important regulator of biological processes in cancer cells. However, the roles and relationship of Rock2 and SCARA5 in renal cell carcinoma (RCC) remain unclear. In this study, we found that Rock2 expression was markedly increased in clinical RCC tissues compared with that in adjacent non-cancerous tissues. High expression of Rock2 was inversely correlated with patient survival in RCC, which indicated that Rock2 may be a prognostic marker in human RCC. In addition, Rock2 knockdown increased SCARA5 expression and suppressed RCC cell proliferation both in vitro and in vivo. Furthermore, we found that the β-catenin/TCF4 pathway contributed to the effect of Rock2 on SCARA5-mediated RCC proliferation. Taken together, these results suggest that this newly identified Rock2-β-catenin/TCF4-SCARA5 axis will provide novel insight into the understanding of the regulatory mechanisms of proliferation in human RCC. - Highlights: • Rock2 is overexpressed in RCC. • Rock2 may be considered a prognostic marker in human RCC. • Rock2 influences RCC proliferation by regulating SCARA5 expression. • Rock2 regulates SCARA5 expression via the β-catenin/TCF4 pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

MicroRNA-7 inhibits cell proliferation of chronic myeloid leukemia and sensitizes it to imatinib in vitro

Highlights: • MiR-7 inhibits cell proliferation and induces apoptosis in CML. • MiR-7 sensitizes K562 cells to imatinib. • MiR-7 directly targets BCR-ABL/PI3K/AKT pathway. MicroRNA is a large class of non-coding small RNA that exerts critical roles in many physiological processes including cell proliferation. MicroRNA-7 (miR-7) has been considered as a tumor suppressor in most malignant tumors versus a tumor promoter in some other ones. However, its role in chronic myeloid leukemia remains unknown. Herein, we found that K562 cell proliferation was largely suppressed when it was stably transfected with miR-7. In accordance with that, apoptosis was also significantly upregulated in miR-7 stably-transfected K562 cells. Moreover, we found that miR-7-overexpressed K562 cells were far more sensitive to imatinib than controls. Further investigations showed that the ABL1 was a direct target of miR-7. Expression level of BCR-ABL and the activity of its downstream PI3K/AKT pathway were significantly reduced in miR-7-transfected cells. Taken together, our results showed that miR-7 inhibited proliferation and promoted apoptosis in K562 cells, and miR-7 might help to sensitize them to imatinib through BCR-ABL/PI3K/AKT signaling in chronic myeloid leukemia.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways

The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. - Highlights: • CHIP is significantly upregulated in thyroid cancer cells. • Overexpression of CHIP facilitates proliferation and tumorigenesis of thyroid cancer cells. • Silencing of CHIP inhibits the proliferation and tumorigenesis of thyroid cancer cells. • CHIP promotes thyroid cancer cell proliferation via activating the MAPK and AKT pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

LncRNA FER1L4 suppresses cancer cell proliferation and cycle by regulating PTEN expression in endometrial carcinoma

Background: Dysregulated long non-coding RNAs (lncRNAs) might exert key roles in pathways associated with endometrial carcinoma (EC) development. This study aims to investigate the new role of lncRNA FER1L4 in EC pathogenesis due to its correlation with phosphatase and tensin homolog (PTEN), one important indicator of EC progression. Methods: Real time PCR was performed to detect the expression of FER1L4 in thirty paired EC samples and two EC cell lines. Plasmid containing FER1L4 was transfected into HEC-50 cells with a relative lower level of FER1L4 expression, followed which PTEN expression and Akt phosphorylation were measured by western blotting. Cell proliferation was analyzed through MTT and colony-formation assays, while cell cycle and apoptosis were determined by flow cytometry. Results: FER1L4 showed significantly downregulation in EC tissues compared to control, which was positively correlated with decreased PTEN expression. Moreover, FER1L4 could promote PTEN expression and inhibit Akt phosphorylation. Additionally, a significant decrease of cell proliferation was observed in FER1L4 overexpressing cells, along with cell cycle arrest at G0/G1 phase and increased proportion of apoptotic cells. Conclusion: FER1L4 not only showed downregulation in EC tissues and cells, but also regulated PTEN expression and Akt signaling, which might contribute to its inhibition on cell proliferation. This study might provide a new potential therapeutic target for EC treatment. - Highlights: •FER1L4 expression was markedly downregulated in EC tissues compared to control. •FER1L4 downregulation was positively correlated with decreased PTEN expression. •FER1L4 could promote PTEN expression and inhibit Akt phosphorylation. • FER1L4 showed significant inhibition on EC cell proliferation. • FER1L4 also induced cell cycle arrest and apoptosis promotion in EC cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Silencing Drp1 inhibits glioma cells proliferation and invasion by RHOA/ ROCK1 pathway

Backgrounds: Dynamin-related protein 1 (Drp1) is a newly discovered therapeutic target for tumor initiation, migration, proliferation, and chemosensitivity. In the present study, we aimed to examine the level of expression and distribution of DRP1 in glioma tissues and explore the concrete mechanism of DRP1 played in glioma. Methods: Expression of DRP1 in glioma tissues was determined by immunohistochemistry staining. The DRP1 gene was knocked down using small interfering RNA, and was overexpressed using plasmids in glioma cells. To assess changes in cell function, in vitro assays for invasion and growth were applied. Protein expression was tested by using Western-blot method. Variation of F-actin in cells was analyzed using immunofluorescence staining. Interactions between proteins were determined by co-immunoprecipitation. Results: The protein expression levels of DRP1 were significantly increased in glioma tissues compared to the normal brain tissues. Down-regulation of DRP1 decreased cell proliferation and invasion, and inhibited the formation of pseudopodias and microvillis. Moreover, a possible link between DRP1 and RHOA was confirmed when interactions between these two proteins were observed in the cells. Conclusions: Our results demonstrated that silencing DRP1 regulated the cytoskeleton remodeling through inhibiting RHOA/ROCK1 pathway, and thus decreased the proliferation and invasion of glioma cells. - Highlights: • DPR1 is significantly increased in glioma tissues. • Down-regulation of DRP1 in glioma cells inhibits cell proliferation. • Down-regulation of DRP1 in glioma cells inhibits cell invasion and induces F-actin remodeling. • Down-regulation of DRP1 inhibits RHOA/ROCK1 pathway in glioma cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Rapamycin regulates the proliferation of Huh7, a hepatocellular carcinoma cell line, by up-regulating p53 expression

Rapamycin, a specific inhibitor of mTOR used extensively as an immunosuppressant, has been expanded recently to cancer therapy, because the mTOR signal is known to be up-regulated in various cancer cells including hepatocellular carcinoma (HCC) cells. In spite of extensive efforts to employ mTOR inhibitors as anti-HCC therapy, they have not yet been approved by the FDA. Because of the heterogeneity and complexity of molecular signaling in HCC, suitable biomarkers should be identified or discovered to improve clinical efficacy of mTOR-specific inhibitors to HCC cells. In this study, the effect of rapamycin was investigated on two different HCC cell lines, Huh7 cells and HepG2 cells. Rapamycin was found to inhibit the proliferation of Huh7 cells but not of HepG2 cells. Moreover, it was found that rapamycin can up-regulate p53 at the protein level, but not affect its transcript. To understand the critical role of p53 in the rapamycin effect, knock-down experiments were performed using small-interfering RNAs (siRNAs). The anti-proliferative effect of rapamycin on Huh7 cells clearly disappeared after blocking p53 production with siRNA, which indicates that p53 is a critical factor in the anti-proliferative effect of rapamycin in HCC cells. The over-expression system of p53 was also employed to mimic the effect of rapamycin and found that cell proliferation was clearly down-regulated by p53 over-expression. Finally, we found that the extracellular signal-regulated kinase 1/2 (ERK1/2) signal was regulated by p53 whose expression was induced by rapamycin. Overall, this study demonstrates that rapamycin inhibited the proliferation of Huh7 cells by up-regulating the expression of p53 and down-regulating the ERK1/2 signal, indicating that p53 is a useful biomarker for anti-cancer therapy using the specific inhibitor of mTOR signal, rapamycin, against hepatocellular carcinoma cells. - Highlights: • Rapamycin inhibits the proliferation of hepatocellular carcinoma cells depending on the expression of p53. • Rapamycin up-regulates p53 at the protein level, but not affect its transcript. • The up-regulation of p53 expression by rapamycin inhibits ERK signal.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

MiR-33a suppresses proliferation of NSCLC cells via targeting METTL3 mRNA

Methyltransferase like 3 (METTL3) was incipiently known as a methyltransferase which was responsible for N{sup 6}-methyladenosine (m{sup 6}A) methylation. METTL3 can promote the expression of several crucial oncoproteins and its high expression enhanced proliferation, survival, and invasion of human lung cancer cells. However, how METTL3 was regulated is seldom understood in non-small-cell lung carcinoma (NSCLC). In the present study, miR-33a was suspicious to target to the 3'-untranslated region (3'UTR) of METTL3 mRNA via in silico prediction. Besides, the expressions of METTL3 were higher in NSCLC tissues than those in adjacent tissues, and METTL3 expressions were positively related to the expressions of miR-33a in NSCLC tissues which confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-33a can directly target to the 3'UTR of METTL3 mRNA which examined by luciferase reporter gene assay. Moreover, we found that miR-33a can reduce the expression of METTL3 at both mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Functionally, miR-33a can reduce the proliferation of A549 and NCI-H460 cells. Conversely, inhibition of miR-33a by anti-miR-33a can rescue that using 4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-ethynyl-2-deoxyuridine (EdU) assay. Similarly, miR-33a can reduce cellular anchorage-independent growth of A549 cells. Additionally, the negative influences of miR-33a on the downstream genes of METTL3 were examined by Western blot analysis. Thus, we concluded that miR-33a can attenuate NSCLC cells proliferation via targeting to the 3'UTR of METTL3 mRNA. Our findings provide new insights into the mechanism of METTL3 regulation by micro RNA, and supports METTL3 as a therapeutic target in NSCLC. - Highlights: • METTL3 expression is negatively correlated with miR-33a. • MiR-33a can directly target to the 3'UTR of METTL3 mRNA. • MiR-33a inhibits NSCLC cells proliferation through decreasing METTL3. • MiR-33a induces the down-regulation of EGFR through targeting METTL3.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell proliferation

Large amount of clinical evidence has demonstrated that insulin resistance is closely related to oncogenesis of endometrial cancer (EC). Despite recent studies showed the up-regulatory role of insulin in G protein-coupled estrogen receptor (GPER/GPR30) expression, GPER expression was not decreased compared to control when insulin receptor was blocked even in insulin treatment. The purpose of this study was to explore the possible mechanism by which insulin up-regulates GPER that drives EC cell proliferation. For this purpose, we first investigated the GPER expression in tissues of endometrial lesions, further explored the effect of GPER on EC cell proliferation in insulin resistance context. Then we analyzed the role of Ten-Eleven Translocation 1 (TET1) in insulin-induced GEPR expression and EC cell proliferation. The results showed that GPER was highly expressed in endometrial atypical hyperplasia and EC tissues. Mechanistically, insulin up-regulated TET1 expression and the latter played an important role in up-regulating GPER expression and activating PI3K/AKT signaling pathway. TET1 mediated GPER up-regulation was another mechanism that insulin promotes EC cell proliferation. - Highlights: • GPER acts as an oncogene to drive EC cell growth in insulin resistance context. • TET1 is associated with insulin-induced GPER expression. • Insulin resistance contributed to EC through TET1-GPER-PI3K/AKT pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Over-expression of CHAF1A in Epithelial Ovarian Cancer can promote cell proliferation and inhibit cell apoptosis

Chromatin Assembly Factor 1, subunit A (CHAF1A) can regulate cell proliferation, DNA repair and epigenetic changes in embryonic stem cells and it has been reported that over-expression of CHAF1A is associated with several human diseases including cancer. However, the expression and function of CHAF1A in Epithelial Ovarian Cancer (EOC) are rarely reported at present. In this study, we found that the positive staining of CHAF1A in EOC was higher than that in normal tissues and over-expression of CHAF1A was strongly associated with cancer stage and lymph node metastasis. Knockdown of CHAF1A by siRNA in EOC inhibited cell proliferation, reduced colony formation, caused G0/G1 phase arrest and promoted cell apoptosis. Taken together, the high expression of CHAF1A promotes cell proliferation and inhibits cell apoptosis and CHAF1A may be developed as a prognosis biomarker and potential therapeutic target of EOC. - Highlights: • CHAF1A expression is significantly elevated in EOC. • CHAF1A is associated with poor clinical outcomes in EOC. • Knockdown CHAF1A inhibits proliferation, induces G0/G1 phase arrest and promotes apoptosis in EOC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

ALG2 regulates glioblastoma cell proliferation, migration and tumorigenicity

Apoptosis-linked gene-2 (ALG-2), also known as programmed cell death 6 (PDCD6), has recently been reported to be aberrantly expressed in various tumors and required for tumor cell viability. The aim of the present study was to investigate whether ALG-2 plays a crucial role in tumor cell proliferation, migration and tumorigenicity. In this study, we examined the expression of PDCD6 in glioblastoma cell lines and found that ALG-2 was generally expressed in glioblastoma cell lines. We also performed an analysis of an online database and found that high expression of ALG-2 was associated with poor prognosis (p = 0.039). We found that over-expression of ALG2 in glioblastoma could inhibit cell proliferation and, conversely, that down-regulation of ALG2 could promote cell proliferation. Further studies showed that over-expression of ALG2 inhibited the migration of tumor cells, whereas down-regulation of ALG2 promoted tumor cell migration. Finally, in vitro and in vivo studies showed that over-expression of ALG2 inhibited the tumorigenic ability of tumor cells, while down-regulation of ALG2 promoted tumor cell tumorigenic ability. In conclusion, ALG2 has a tumor suppressive role in glioblastoma and might be a potential target for the treatment of glioblastoma. - Highlights: • Low ALG2 expression is indicative of poor prognosis in glioblastoma patients. • ALG2 is required for cell proliferation in GBM cells. • ALG2 is involved in GBM cell migration. • ALG2 is involved in GBM cell self-renewal and tumorigenesis in vitro and in vivo.

60 APPLIED LIFE SCIENCES↗