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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 685 records · Page 38
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

MicroRNA-202 inhibits tumor progression by targeting LAMA1 in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies in the gastrointestinal tract. Emerging studies have indicated that microRNAs (miRNAs) are strongly implicated in the development and progression of ESCC. Here, we focused on the function and the underlying molecular mechanism of miR-202 in ESCC. The results showed that miR-202 was significantly down-regulated in ESCC tissues and cell lines. Overexpression of miR-202 in ECa-109 and KYSE-510 cells markedly suppressed cell proliferation and cell migration, and induced cell apoptosis. Furthermore, laminin α1 (LAMA1) expression was frequently positive in ESCC tissues and inversely correlated with miR-202 expression. Then we demonstrated that miR-202 targeted 3'-untranslated region (UTR) of LAMA1 and inhibited its protein expression. Additionally, LAMA1 overexpression rescued the proliferation inhibition and cell apoptosis elevation induced by miR-202. MiR-202 also inhibited the protein expression of p-FAK and p-Akt, which were all reversed by LAMA1 overexpression. Taken together, these findings suggest that miR-202 may function as a novel tumor suppressor in ESCC by repressing cell proliferation and migration, and its biological effects may attribute the inhibition of LAMA1-mediated FAK-PI3K-Akt signaling. - Highlights: • Expression of miR-202 was decreased in ESCC tissues and cell lines. • MiR-202 overexpression inhibited ESCC cell growth and induced apoptosis. • MiR-202 directly targeted LAMA1 in ESCC. • The LAMA1-FAK-PI3K signaling mediated the suppressive role of miR-202.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis

Several reports have indicated a role for the members of the G12 family of heterotrimeric G proteins (Gα12 and Gα13) in oncogenesis and tumor cell growth. The aims of the present study were to evaluate the role of G12 signaling in cervical cancer. We demonstrated that expression of the G12 proteins was highly upregulated in cervical cancer cells. Additionally, expression of the activated forms of Gα12/Gα13 but not expression of activated Gαq induced cell invasion through the activation of the RhoA family of G proteins, but had no effect on cell proliferation in the cervical cancer cells. Inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) blocked thrombin-stimulated cell invasion, but did not inhibit cell proliferation in cervical cells, whereas the inhibition of Gαq (RGS2) had no effect. Furthermore, G12 signaling was able to activate Rho proteins, and this stimulation was inhibited by p115-RGS, and Gα12-induced invasion was blocked by an inhibitor of RhoA/B/C (C3 toxin). Pharmacological inhibition of JNK remarkably decreased G12-induced JNK activation. Both a JNK inhibitor (SP600125) and a ROCK inhibitor (Y27632) reduced G12-induced JNK and c-Jun activation, and markedly inhibited G12-induced cellular invasion. Collectively, these findings demonstrate that stimulation of G12 proteins is capable of promoting invasion through RhoA/ROCK-JNK activation. -- Highlights: •Gα12/Gα13 is upregulated in cervical cancer cell lines. •Gα12/Gα13 is not involved in cervical cancer cell proliferation. •Gα12/Gα13 promotes cervical cancer cell invasion. •The role of Rho G proteins in G12-promoted cervical cancer cell invasion. •G12 promotes cell invasion through activation of the ROCK-JNK signaling axis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MicroRNA-24 promotes 3T3-L1 adipocyte differentiation by directly targeting the MAPK7 signaling

Over the past years, MicroRNAs (miRNAs) act as a vital role in harmony with gene regulation and maintaining cellular homeostasis. It is well testified that miRNAshave been involved in numerous physiological and pathological processes, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes, and it is tightly modulated by a series of transcription factors such as peroxisome proliferator-activated receptor γ (PPAR-γ) and sterol regulatory-element binding proteins 1 (SREBP1). However, the molecular mechanisms underlying the connection between miRNAs and adipogenesis-related transcription factors remain obscure. In this study, we unveiled that miR- 24 was remarkably upregulated during 3T3-L1 adipogenesis. Overexpression of miR-24 significantly promoted 3T3-L1 adipogenesis, as evidenced by its ability to increase the expression of PPAR-γ and SREBP1, lipid droplet formation and triglyceride (TG) accumulation. Furthermore, we found that neither ectopic expression of miR-24nor miR-24 inhibitor affect cell proliferation and cell cycle progression. Finally, we demonstrated that miR-24 plays the modulational role by directly repressing MAPK7, a key number in the MAPK signaling pathway. These data indicate that miR-24 is a novel positive regulator of adipocyte differentiation by targeting MAPK7, which provides new insights into the molecular mechanism of miRNA-mediated cellular differentiation. -- Highlights: •We firstly found miR-24 was upregulated in 3T3-L1 pre-adipocytes differentiation. •miR-24 promoted 3T3-L1 pre-adipocytes differentiation while silencing the expression of miR-24 had an opposite function. •miR-24 regulated 3T3-L1 differentiation by directly targeting MAPK7 signaling pathway. •miR-24did not affect 3T3-L1 pre-adipocytes cellular proliferation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Inhibition of VEGF-dependent angiogenesis by the anti-CD82 monoclonal antibody 4F9 through regulation of lipid raft microdomains

CD82 (also known as KAI1) belongs to the tetraspanin superfamily of type III transmembrane proteins, and is involved in regulating cell adhesion, migration and proliferation. In contrast to these well-established roles of CD82 in tumor biology, its function in endothelial cell (EC) activity and tumor angiogenesis is yet to be determined. In this study, we show that suppression of CD82 negatively regulates vascular endothelial growth factor (VEGF)-induced angiogenesis. Moreover, we demonstrate that the anti-CD82 mAb 4F9 effectively inhibits phosphorylation of VEGF receptor 2 (VEGFR2), which is the principal mediator of the VEGF-induced angiogenic signaling process in tumor angiogenesis, by regulating the organization of the lipid raft microdomain signaling platform in human EC. Our present work therefore suggests that CD82 on EC is a potential target for anti-angiogenic therapy in VEGFR2-dependent tumor angiogenesis. -- Highlights: •Knockdown of CD82 decreases EC migration, proliferation and angiogenesis. •Anti-CD82 mAb 4F9 inhibits EC migration, proliferation and angiogenesis. •4F9 inhibits VEGFR2 phosphorylation via control of CD82 distribution in lipid rafts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Methylation of miR-145a-5p promoter mediates adipocytes differentiation

MicroRNAs (miRNAs, miR) play important roles in adipocyte development. Recent studies showed that the expression of several miRNAs is closely related with promoter methylation. However, it is not known whether miRNA mediates adipocytes differentiation by means of DNA methylation. Here, we showed that miR-145a-5p was poorly expressed in adipose tissue from mice fed a high fat diet (HFD). Overexpression or inhibition of miR-145a-5p was unfavorable or beneficial, respectively, for adipogenesis, and these effects were achieved by regulating adipocyte-specific genes involved in lipogenic transcription, fatty acid synthesis, and fatty acid transportation. Particularly, we first suggested that miR-145a-5p mimics or inhibitors promoted or repressed adipocytes proliferation by regulating p53 and p21, which act as cell cycle regulating factors. Surprisingly, the miR-145a-5p-repressed adipocyte differentiation was enhanced or rescued when cells treated with 5-Aza-dC were transfected with miR-145a-5p mimics or inhibitors, respectively. These data indicated that, as a new mean to positively regulate adipocyte proliferation, the process of miR-145a-5p-inhibited adipogenesis may be regulated by DNA methylation. -- Highlights: •MiR-145a-5p promotes adipocytes proliferation. •MiR-145a-5p is negatively correlated with obesity. •MiR-145a-5p mediates adipocytes differentiation via regulating pathway related adipocytes differentiation. MiR-145a-5p mediating adipocytes differentiation was regulated by DNA methylation.

60 APPLIED LIFE SCIENCES↗
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↗