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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 829 records · Page 46
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling

Aberration of signaling pathways by genetic mutations or alterations in the surrounding tissue environments can result in tumor development or metastasis. However, signaling molecules responsible for these processes have not been completely elucidated. Here, we used mouse Lewis lung carcinoma cells (LLC) to explore the mechanism by which the oncogenic activity of Semaphorin3A (Sema3A) signaling is regulated. Sema3A knockdown by shRNA did not affect apoptosis, but decreased cell proliferation in LLCs; both the mammalian target of rapamycin complex 1 (mTORC1) level and glycolytic activity were also decreased. In addition, Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation by oligomycin, but conferred resistance to decreased cell viability induced by glucose starvation. Furthermore, recombinant SEMA3A rescued the attenuation of cell proliferation and glycolytic activity in LLCs after Sema3A knockdown, whereas mTORC1 inhibition by rapamycin completely counteracted this effect. These results demonstrate that Sema3A signaling exerts its oncogenic effect by promoting an mTORC1-mediated metabolic shift from oxidative phosphorylation to aerobic glycolysis. -- Highlights: •Sema3A knockdown decreased proliferation of Lewis lung carcinoma cells (LLCs). •Sema3A knockdown decreased mTORC1 levels and glycolytic activity in LLCs. •Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation. •Sema3A promotes shift from oxidative phosphorylation to aerobic glycolysis via mTORC1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

17β-estradiol regulates the differentiation of cementoblasts via Notch signaling cascade

Estrogen has been well recognized as a key factor in the homeostasis of bone and periodontal tissue, but the way it regulates the activities of cementoblasts, the cell population maintaining cementum has not been fully understood. In this study, we examined the expression of estrogen receptor in OCCM-30 cells and the effect of 17β-estradiol (E2) on the proliferation and differentiation of OCCM-30 cells. We found that both estrogen receptor α and β were expressed in OCCM-30 cells. E2 exerted no significant influence on the proliferation of OCCM-30 cells, but inhibited the transcription and translation of BSP and Runx2 in the early phase of osteogenic induction except the BSP mRNA. Afterwards in the late phase of osteogenic induction, E2 enhanced the transcription and translation of BSP and Runx2 and promoted the calcium deposition. In addition, the expression level of Notch1, NICD and Hey1 mRNAs responded to exogenous E2 in a pattern similar to that of the osteoblastic markers. DAPT could attenuate the effect of E2 on the expression of osteoblastic markers. These findings indicated that E2 might regulate the differentiation of cementoblasts via Notch signaling. - Highlights: • 17β-estradiol showed no significant effect on the proliferation of cementoblasts. • 17β-estradiol promoted the osteoblastic differentiation of cementoblasts despite of an early transient inhibition. • Notch signaling was regulated by 17β-estradiol and was responsible for mediating the effect of E2 on cementoblasts. • Hey1 might display an opposite expression pattern to Notch signaling in certain circumstances.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, we examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. - Highlights: • ID4 expression induces AR expression in PC3 cells, which generally lack AR. • ID4 expression increased apoptosis and decreased cell proliferation and invasion. • Overexpression of ID4 reduces tumor growth of subcutaneous xenografts in vivo. • ID4 induces p21 and FKBP51 expression- co-factors of AR tumor suppressor activity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

IRF3 is involved in human acute myeloid leukemia through regulating the expression of miR-155

Acute myeloid leukemia (AML) is a serious disease of the hematopoietic system characterized by de-differentiation and uncontrolled proliferation of immature hematopoietic precursor cells in the bone marrow. However, the underlying mechanism of AML development remains largely unknown. Here in this study, we report the function of IRF3, a member of the interferon-regulatory factor (IRF) family, in human AML. We first show that IRF3 mRNA and protein levels are significantly up-regulated in human AML compared with healthy donors. IRF3 knockdown inhibits cellular proliferation and colony formation in OCI/AML-2 and OCI/AML-3 cells. In addition, IRF3 knockdown induces apoptosis of OCI/AML-2 and OCI/AML-3 cells, whereas IRF3 overexpression promotes cell survival. Further mechanism study shows that IRF3 is positively correlated with miR-155, which is considered as an oncogenic microRNA in AML. We show that IRF3 binds to the promoter of miR-155 and promotes the expression of miR-155 in OCI/AML-2 and OCI/AML-3 cells. In conclusion, our evidence show that IRF3 overexpression in AML promotes cell growth and survival, and miR-155 is involved, indicating that IRF3 may be a potential new biomarker and therapeutic target for AML. - Highlights: • IRF3 is overexpressed in human AML. • IRF3 promotes AML cell proliferation and colony formation. • IRF3 maintains cell survival of AML cells. • IRF3 regulates the expression of miR-155.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Inorganic polyphosphate triggers upregulation of interleukin 11 in human osteoblast-like SaOS-2 cells

Polyphosphate (polyP) is abundant in bone but its roles in signaling and control of gene expression remain unclear. Here, we investigate the effect of extracellular polyP on proliferation, migration, apoptosis, gene and protein expression in human osteoblast-like SaOS-2 cells. Extracellular polyP promoted SaOS-2 cell proliferation, increased rates of migration, inhibited apoptosis and stimulated the rapid phosphorylation of extracellular-signal-regulated kinase (ERK) directly through basic fibroblast growth factor receptor (bFGFR). cDNA microarray revealed that polyP induced significant upregulation of interleukin 11 (IL-11) at both RNA and protein levels. - Highlights: • Inorganic polyphosphate promotes osteoblast cell proliferation and migration rate. • Inorganic polyphosphate inhibits apoptosis. • Inorganic polyphosphate phosphorylates ERK. • Inorganic polyphosphate upregulates interleukin 11 at RNA and protein levels.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Cox-2 promotes mesenchymal stem cells differentiation into cardiocytes by activating JNK and ERK pathway

Coronary heart disease and various cardiomyopathys may cause myocardial damage, reducing the number of myocardial cells with complete functions. Cyclooxygenase 2 (Cox-2) has been reported participating in a variety of pathological processes, including tumor invasion and metastasis. In this study, we sought to explore the correlation of Cox-2 with MSCs proliferation, and migration. MSCs were transfected with pcDNA-Cox2 and NS-398 to promote or inhibit the expression of Cox2. Then, MTT, transwell, qRT-PCR and western blot were used to test the influence of Cox2 on cells proliferation, cells migration and cell viability of mesenchymal stem. The results show that Cox-2 promotes directional differentiation of myocardial cells and the overexpression of cox-2 can activate the key factors of JNK and ERK signaling pathway, promotes myocardial cell directional differentiation. - Highlights: • Cox-2 promotes MSCs cell proliferation and migration. • Cox-2 promotes expression of MSCs differentiation marker gene. • Cox-2 activates the JNK and ERK signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

High expression of CREPT promotes tumor growth and is correlated with poor prognosis in colorectal cancer

CREPT (cell cycle-related and expression elevated protein in tumor) is highly expressed in many kinds of cancer, and has been shown to be prognostic in certain cancers. However, the clinical significance of CREPT in colorectal cancer (CRC) has not been sufficiently investigated. In this study, we examined the CREPT expression in 225 clinical CRC tissues and paired adjacent normal tissues, and analyzed the correlation between CREPT expression and other clinicopathological features. We also evaluated the biological function of CREPT both in vitro and in vivo using knockdown or overexpressing CRC cells. Our results showed that CREPT expressed in 175 of 225 (77.8%) CRC patients and the CREPT expression was significantly associated with tumor differentiation (P = 0.000), Dukes' stages (P = 0.013) and metastasis (P = 0.038). Patients with high CREPT expression tended to have shorter survival time. Multivariate analysis showed that positive CREPT expression can be used as an independent predictor for CRC prognosis. CREPT knockdown cells showed inhibited cell proliferation and arrested cell cycle, while CREPT overexpressing cells showed increased proliferation and promoted cell cycle. In addition, CREPT overexpression significantly promoted tumor growth in vivo. Mechanism study showed that CREPT may regulate cell proliferation and cell cycle through the regulation on cyclin D3, CDK4 and CDK6. - Highlights: • CREPT expression was associated with decreased overall survival in CRC. • CREPT expression is correlated with tumor progression in CRC. • Overexpression of CREPT promoted tumor growth both in vitro and in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

CUL4A functions as an oncogene in ovarian cancer and is directly regulated by miR-494

Cullin 4A (CUL4A), as a well-defined oncogene, has been reported to be upregulated in ovarian cancer clinically. However, the biological functions of CUL4A and the molecular mechanism underlying its upregulation in ovarian cancer remains unknown throughly. Here, we show that expression of CUL4A is significantly higher in ovarian cancer tissues compared to corresponding non-cancerous tissues. Moreover, silencing of CUL4A by siRNA markedly inhibits cell proliferation, invasion and epithelial-mesenchymal transition (EMT). We identified CUL4A as a novel target gene of miR-494. Further investigations showed that miR-494 was remarkably downregulated and correlated with poor prognosis in ovarian cancer. Overexpression of miR-494 inhibited proliferation, migration, invasion and EMT of ovarian cancer cells by directly suppressing CUL4A expression. Therefore, our findings indicate that miR-494/CUL4A axis is important in the control of ovarian cancer tumorigenesis. - Highlights: • CUL4A is upregulated in ovarian cancer and knockdown of CUL4A inhibits cell proliferation, invasion and EMT. • MiR-494 directly targets CUL4A 3′UTR. • MiR-494 is frequently downregulated and correlated with poor prognosis in ovarian cancer. • CUL4A is involved in miR-494-induced tumor suppressive effects.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

A human Fab exclusively binding to the extracellular domain of LMP2A

In the areas of North Africa, Southeast Asia as well as South China, Nasopharyngeal carcinoma (NPC) is among the most widespread cancers. Plenty of research findings confirmed that Epstein-Barr virus (EBV) played a crucial role in NPC. EBV-encoded Latent membrane protein 2A (LMP2A) which continuously expressed in cell membrane protein induced an epithelial-mesenchymal transition and increased the number of side population stem-like cancer cells in NPC. This reveals that LMP2A could contribute to the development and recurrence in NPC. Above evidences suggest that LMP2A could be the potential target molecule in the treatment of NPC. In the current study, a novel human antibody Fab (Fab29) against the extracellular domain of LMP2A was produced with success. Through immunofluorescence experiment it was proved that human antibody Fab29 exclusively combined the surface of SUNE cells (LMP2A-positive). Then flow cytometry result exhibited that the fluorescent intensities of SUNE cells and CNE cells were distinct (96.89% and 0.02% respectively). After that, it was shown by affinity test that the Fab29 fragment had high affinity (KD (M) 1.79E-09) with LMP2A. It was also revealed by immunohistochemical analysis that the Fab29 fragment could combine with LMP2A-positive human NPC tissues in comparison with the control group. Finally, the MTT result indicated that the Fab29 fragment could inhibit the proliferation of LMP2A-positive NPC cells. The inhibiting rate to SUNE cell proliferation reached a peak by Fab29 (19.67%) compared with unrelated Fab and CNE with Fab29 at a concentration of 500 μg/L in first 24 h and in the next 24 h the inhibition rate grew to 22.54%. In brief, it was shown that Fab29, a characteristic human antibody, could recognize LMP2A protein and inhibit the proliferation of LMP2A-expressing NPC cells in vitro.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

MicroRNA-187 regulates gastric cancer progression by targeting the tumor suppressor CRMP1

Aberrant expression of microRNAs contributes to the initiation and progression of numerous human cancers. The underlying effects and molecular mechanisms of microRNA-187 (miR-187) in gastric cancer (GC) remain unclear. The present study reports that miR-187 was significantly overexpressed in GC tissues compared to that in non-tumor tissues and was associated with malignant clinical factors such as depth of invasion (P = 0.005), tumor size (P = 0.024), lymph node metastasis (P = 0.048), and TNM stage (P = 0.035). Additionally, miR-187 promoted tumor growth in vivo, and significantly increased migration, invasion, and proliferation, but inhibited apoptosis in GC cells. It was found that collapsin response mediator protein 1 (CRMP1), a tumor suppressor, was a direct downstream target of miR-187 in GC. Furthermore, CRMP1 silencing resulted in similar effects on cell proliferation, migration, and apoptosis as those of miR-187 overexpressing GC cells. Additionally, the effects of miR-187 inhibitor on cell migration and cell apoptosis were reversed by CRMP1 downregulation. In summary, miR-187 promotes tumor progression by regulating CRMP1 expression in GC and may thus be a potential prognostic marker and a therapeutic target in GC. - Highlights: • miR-187 was significantly overexpressed in GC tissues and associated with malignant clinical factors. • miR-187 significantly increased migration, invasion, and proliferation, but inhibited apoptosis in GC cells. • CRMP1 tumor suppressor is a direct target of miR-187 in GC. • Overexpression of miR-187 promoted GC progression by targeting tumor suppressor gene CRMP1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

SPOCK1 is up-regulated and promotes tumor growth via the PI3K/AKT signaling pathway in colorectal cancer

SPOCK1 encodes a Ca{sup 2+}-binding matricellular glycoprotein which plays an oncogenic role in cancer cells. However, the role of SPOCK1 in the pathogenesis of colorectal cancer (CRC) has not been determined. Here, SPOCK1 was found higher expressed in CRC tissues than that of adjacent normal tissues. Furthermore, up-regulated expression of SPOCK1 in CRC patients was associated with tumor size and TNM stage. In addition, we observed that the depletion of SPOCK1 inhibited proliferation in vitro and tumorigenicity in vivo and promoted apoptosis in cell culture. Our data suggest that inactivation of PI3K/Akt signaling pathway was involved in down-regulation of SPOCK1-mediated suppression of tumor cell proliferation. These results suggest that SPOCK1 expression is correlated with malignant features of CRC and may serve as potential therapeutic and preventive strategies for CRC. - Highlights: • SPOCK1 expression is significantly up-regulated in CRC tissues and associated with tumor size and TMN stage. • Down-regulation of SPOCK1 suppresses CRC cell proliferation both in vitro and in vivo. • SPOCK1 stimulates the PI3K/AKT signaling pathway to inhibit cell apoptosis and promote tumor growth.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Effects of C-terminal amelogenin peptides on the metabolism of osteoblasts

Objectives: Amelogenins, enamel matrix proteins secreted by ameloblasts, comprise 90% of the developing extracellular enamel matrix. Recent evidence suggests that amelogenins might induce the proliferation of various cells. However, the residues comprising the active site of amelogenin remain unclear. Therefore, this study aimed to examine the effects of a human amelogenin C-terminal peptide (amgCP) on the metabolism of osteoblasts. Materials and methods: Mouse calvarial osteoblastic cells (MC3T3-E1) were cultured and treated with amgCP. Cell proliferation was measured using MTS and BrdU assays. After confluence was reached, the cells were cultured in osteogenic differentiation medium and treated with 0, 100, or 1000 ng/ml amgCP. Cell differentiation activity was examined by real-time PCR, western blotting, and ALP activity. Mineralization was evaluated by Alizarin red staining. Results: Cell numbers of MC3T3-E1 were significantly (P < 0.05) increased by treatment with 1000 ng/ml amgCP as compared to the control group at 4 and 6 days. In addition, the proliferative activity of MC3T3-E1 was significantly enhanced by treatment with 100 or 1000 ng/ml amgCP. The mRNA levels and protein expressions of ALP and BSP were not changed by treatment with amgCP as compared to the non-treated controls on days 7 and 14. The osteogenic differentiation of MC3T3-E1 cells was not affected by treatment with amgCP as compared with untreated controls. Conclusion: The C-terminus of amelogenin promotes the proliferation of MC3T3-E1 cells, indicating the possible utility of the C11 peptide in bone-tissue regeneration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Inhibition of TRPC3 downregulates airway hyperresponsiveness, remodeling of OVA-sensitized mouse

Airway hyperresponsiveness (AHR), airway remodeling and inflammation are the fundamental pathological alterations that occur in asthma. Transient receptor potential canonical 3 (TRPC3) has been implicated in diverse functions of airway smooth muscle cells (ASMCs) in asthma. However, the underlying mechanisms remain incompletely understood. We investigated the mRNA and protein expression of TRPC3 in ASMCs from normal and OVA-sensitized mouse. And the effects of inhibition or knockdown of TRPC3 with Ethyl-1- (4- (2,3,3-trichloroacrylamide) phenyl) −5 - (trifluoromethyl) -1H -pyrazole -4-carboxylate (Pyr3) and lentiviral shRNA on OVA-sensitized mouse AHR, airway remodeling, circulating inflammatory cytokines, cell proliferation and migration. We found that TRPC3 mRNA and protein expression levels were significantly increased in ASMCs from OVA-sensitized mouse. Inhibiting TRPC3 with continuous subcutaneous administration of Pyr3 decreased enhanced pause (Penh) of OVA-sensitized mouse. Meanwhile, both Pyr3 and lentiviral shRNA treatment of ASMCs in OVA-sensitized mouse significantly decreased their proliferation and migration. These results suggest that TRPC3 plays a critical role in asthma and represents a promising new target for asthma treatment. - Highlights: • Penh, airway remodeling and the gene expression and protein of TRPC3 are increased in OVA-sensitized mice. • Inhibition of TRPC3 suppresses the OVA-sensitized mice Penh and airway remodeling. • Inhibition of TRPC3 decreases OVA-sensitized mice ASMC proliferation and migration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Nongenomic effects of 1α,25-dihydroxyvitamin D{sub 3} on cartilage formation deduced from comparisons between Cyp27b1 and Vdr knockout mice

The active form of vitamin D, 1α,25-dihydroxyvitamin D{sub 3} (1α,25D{sub 3}), plays an important role in the maintenance of calcium (Ca) homeostasis, bone formation, and cell proliferation and differentiation via nuclear vitamin D receptor (VDR). It is formed by the hydroxylation of vitamin D at the 1α position by 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) in the kidney. However, Cyp27b1{sup −/−} mice, deficient in CYP27B1, and VDR-deficient mice (Vdr{sup −/−}) have not been extensively examined, particularly in a comparative framework. To clarify the physiological significance of 1α,25D{sub 3} and VDR, we produced Cyp27b1{sup −/−} mice and compared their phenotypes with those of Vdr{sup −/−} mice. Cyp27b1{sup −/−} mice exhibited hypocalcemia, growth defects, and skeletogenesis dysfunction, similar to Vdr{sup −/−} mice. However, unlike Cyp27b1{sup −/−} mice, Vdr{sup −/−} mice developed alopecia. Cyp27b1{sup −/−} mice exhibited cartilage mass formation and had difficulty walking on hindlimbs. Furthermore, a phenotypic analysis was performed on Cyp27b1{sup −/−} mice provided a high Ca diet to correct for the Ca metabolic abnormality. In addition, the effects of 1α,25D{sub 3} that are not mediated by Ca metabolic regulatory activity were investigated. Even when the blood Ca concentration was corrected, abnormalities in growth and cartilage tissue formation did not improve in Cyp27b1{sup −/−} mice. These results suggested that 1α,25D{sub 3} directly controls chondrocyte proliferation and differentiation. Using Cyp27b1{sup −/−} mice produced in this study, we can analyze the physiological effects of novel vitamin D derivatives in the absence of endogenous 1α,25D{sub 3}. Accordingly, this study provides a useful animal model for the development of novel vitamin D formulations that are effective for the treatment and prevention of osteoporosis. - Highlights: • We produced Cyp27b1{sup −/−} mice and analyzed their phenotypes. • Vdr{sup −/−} mice exhibited alopecia and Cyp27b1{sup −/−} mice exhibited cartilage dysplasia. • Maintenance of the hair cycle is associated with 25D{sub 3} via Vdr. • 1α,25D{sub 3} controls chondrocyte proliferation and differentiation independent of Vdr.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

miR-214 down-regulates ARL2 and suppresses growth and invasion of cervical cancer cells

Increasing evidence has shown that miRNAs are implicated in carcinogenesis and can function as oncogenes or tumor suppressor genes in human cancers. In this study, we confirmed that miR-214 is frequently down-regulated in cervical cancer compared with normal cervical tissues. Ectopic expression of miR-214 suppressed proliferation, migration and invasion of HeLa and C33A cervical cancer cells. Bioinformatics analysis revealed that ADP ribosylation factor like 2 (ARL2) was a potential target of miR-214 and was remarkably up-regulated in cervical cancer. Knockdown of ARL2 markedly inhibited cervical cancer cell proliferation, migration and invasion, similarly to over-expression of miR-214, indicating that ARL2 may function as an oncogene in cervical cancer. In conclusion, our study revealed that miR-214 acts as a tumor suppressor via inhibiting proliferation, migration and invasion of cervical cancer cells through targeting ARL2, and that both miR-214 and ARL2 may serve as prognostic or therapeutic targets for cervical cancer. - Highlights: • miR-214 targets ARL2. • ARL2 maybe an oncogene in cervical cancer. • ARL2 rescues miR-214.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

TEAD4-YAP interaction regulates tumoral growth by controlling cell-cycle arrest at the G1 phase

TEA domain transcription factor 4 (TEAD4), which has critical functions in the process of embryonic development, is expressed in various cancers. However, the important role of TEAD4 in human oral squamous cell carcinomas (OSCCs) remain unclear. Here we investigated the TEAD4 expression level and the functional mechanism in OSCC using quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. Furthermore, TEAD4 knockdown model was used to evaluate cellular proliferation, cell-cycle analysis, and the interaction between TEAD4 and Yes-associated protein (YAP) which was reported to be a transcription coactivator of cellular proliferation. In the current study, we found that TEAD4 expression increased significantly in vitro and in vivo and correlated with tumoral size in OSCC patients. TEAD4 knockdown OSCC cells showed decreased cellular proliferation resulting from cell-cycle arrest in the G1 phase by down-regulation of cyclins, cyclin-dependent kinases (CDKs), and up-regulation of CDK inhibitors. We also found that the TEAD4-YAP complex in the nuclei may be related closely to transcriptions of G1 arrest-related genes. Taken together, we concluded that TEAD4 might play an important role in tumoral growth and have potential to be a therapeutic target in OSCCs. - Highlights: • TEAD4 contributes to tumor progression in OSCCs. • TEAD4 knockdown results in cell-cycle arrest at the G1phase in OSCC cells. • In TEAD4 knockdown cells, the amount of YAP in the nucleus decreases. • Activation of the TEAD4-YAP complex is an important factor in OSCC tumor growth. • TEAD4 might be a critical biomarker and a therapeutic target for OSCCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Aquaporin 3 facilitates tumor growth in pancreatic cancer by modulating mTOR signaling

Aquaporins (AQP) have been demonstrated to be dysregulated in many human cancers and is thought to be involved in pancreatic carcinogenesis and progression. However, the oncogenic roles and underlying mechanism of AQP in pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. In this study, by data mining of TCGA dataset and CCLE database, we identified that AQP3 is the major AQP expressed in PDAC. Then, the microRNA-874, was demonstrated to be a key regulator of AQP3 expression in PDAC cells. Genetic silencing of AQP3 expression had pronounced effects on cell proliferation and apoptosis of the PDAC cell lines BXPC3 and HPAFII. Introduction of microRNA-874 suppressed cell proliferation and promoted cell apoptosis, whereas inhibition of microRNA-874 had the opposite effect. Mechanistically, by a large-scale proteomic analysis, we revealed that AQP3 was significantly associated the activity of mTOR signaling. Moreover, modulation of AQP3 or microRNA-874 altered mTOR activity as demonstrated by the phosphorylation level of mTOR and its downstream target S6. Taken together, our data, as a proof of principle, suggest that AQP3 can promote tumor growth of pancreatic cancer cells by activating the Mtor signaling pathway and provide a potential therapeutic target in the treatment of PDAC. - Highlights: • Dysregulated expression of AQP3 is induced by miR-874 in pancreatic cancer. • miR-874-AQP3 axis is involved in cell proliferation and apoptosis of pancreatic cancer cells. • AQP3 correlates increased mTOR activity in pancreatic cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Peroxiredoxin 5 promotes the epithelial-mesenchymal transition in colon cancer

Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The high mortality rate of patients with colon cancer is due to cancer cell invasion and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be overexpressed in various tumor tissues, and involved to be responsible for tumor progression. However, the exact role of PRX5 in colon cancer remains to be investigated enhancing proliferation and promoting EMT properties. In this study, we constructed stably overexpressing PRX5 and suppressed PRX5 expression in CRC cells. Our results revealed that PRX5 overexpression significantly enhanced CRC cell proliferation, migration, and invasion. On the other hand, PRX5 suppression markedly inhibited these EMT properties. PRX5 was also demonstrated to regulate the expression of two hallmark EMT proteins, E-cadherin and Vimentin, and the EMT-inducing transcription factors, Snail and Slug. Moreover, in the xenograft mouse model, showed that PRX5 overexpression enhances tumor growth of CRC cells. Thus, our findings first provide evidence in CRC that PRX5 promotes EMT properties by inducing the expression of EMT-inducing transcription factors. Therefore, PRX5 can be used as a predictive biomarker and serves as a putative therapeutic target for the development of clinical treatments for human CRC. - Highlights: • PRX5 promoted colorectal cancer cell proliferation. • PRX5 enhanced EMT properties in colorectal cancer. • PRX5 mediated the EMT by inducing the expression of Snail and Slug. • PRX5 promoted tumor growth of colorectal cancer cells.

60 APPLIED LIFE SCIENCES↗