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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 631 records · Page 35
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DOE OSTI2016

MicroRNA-367 is a potential diagnostic biomarker for patients with esophageal squamous cell carcinoma

Purpose: In this study, we investigated whether microRNA-367 (miR-367) may serve as a circulating biomarker and tumor oncogene in esophageal squamous carcinoma (ESCC). Methods: Circulating serum miR-367 was compared by quantitative RT-PCR (qRT-PCR) between 35 ESCC patients and 35 normal control patients, as well paired ESCC tumor tissues and adjacent non-tumor esophageal epithelial tissues in 46 patients. The correlation between serum miR-367 and clinicopathological properties of ESCC patients was assessed. The overall survival (OS) was assessed by Kaplan–Meier method and compared by log-rank test between patients with high serum miR-367 and low serum miR-367. The possibility of miR-367 being independent prognostic factor for ESCC was also assessed. Furthermore, lentivirus-mediated miR-367 downregulation was conducted in ESCC cell lines Kyse30 and TE-1 cells to assess the possible oncogenic effect of miR-367 on ESCC proliferation and cell cycle transition in vitro. Results: MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients, whereas downregulated in ESCC patients after the treatments of esophagectomy and chemotherapy. Serum miR-367 was found to be closely correlated with the clinicopathological properties of differentiation grades, clinical stage and tumor metastasis in ESCC patients. Serum miR-367 was also confirmed to be associated with OS, as well as serving independent prognostic factor in ESCC patients. Moreover, lentivirus-induced miR-367 downregulation inhibited cancer growth and cell cycle transition in Kyse30 and TE-1 cells. Conclusion: MiR-367 is a potential biomarker for ESCC and may act as an oncogene in regulating ESCC development. - Highlights: • MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients. • MiR-367 was downregulated in ESCC patients after esophagectomy or chemotherapy. • Serum miR-367 was correlated with the clinicopathological properties of ESCC patients. • Serum miR-367 was associated with OS in ESCC patients. • lentivirus-induced miR-367 downregulation inhibited ESCC growth and cell cycle transition.

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

Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by targeting the Notch2 oncogene and correlates with good prognosis in patients with glioblastoma multiforme

Glioblastoma stem-like cells (GSCs) are responsible for the initiation and progression of glioblastoma multiforme (GBM), and microRNAs (miRNAs) play an important role in this disease. However, the mechanisms underlying the role of miRNAs in the stemness of GSCs have not been completely elucidated. We previously showed that miR-181a is downregulated in GBM and may predict prognosis in patients with this disease. Here, we demonstrate that the upregulation of miR-181a suppressed GSC formation and inhibited GBM tumorigenesis by targeting the Notch2 oncogene. We found that miR-181a was downregulated in GSCs derived from human glioblastoma U87MG and U373MG cells. The high expression of miR-181a inhibited the levels of stemness-related markers CD133 and BMI1, attenuated sphere proliferation, promoted cell apoptosis, and reduced the tumorigenicity of GSCs. MiR-181a decreased the expression of Notch2 by targeting the 3’-untranslated region of its mRNA. Notch2 overexpression inhibited the effects of miR-181a downregulation on GSCs, and was negatively correlated with miR-181a expression. Moreover, high Notch2 expression together with low miR-181a expression was correlated with a shorter median overall survival for GBM patients. Together, these data show that miR-181a may play an essential role in GSC formation and GBM progression by targeting Notch2, suggesting that Notch2 and miR-181a have potential prognostic value as tumor biomarkers in GBM patients. - Highlights: • MiR-181a suppressed GSC formation and GBM tumorigenesis by targeting Notch2. • Notch2 and miR-181a expression were correlated with OS for GBM patients. • Notch2 and miR-181a have potential prognostic value in GBM patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Identification and molecular cloning of novel transcripts of the human kallikrein-related peptidase 10 (KLK10) gene using next-generation sequencing

Tissue kallikrein and kallikrein-related peptidases (KLKs) form the largest group of serine proteases in the human genome, sharing many structural and functional characteristics. Multiple alternative transcripts have been reported for the most human KLK genes, while many of them are aberrantly expressed in various malignancies, thus possessing significant prognostic and/or diagnostic value. Alternative splicing of cancer-related genes is a common cellular mechanism accounting for cancer cell transcriptome complexity, as it affects cell cycle control, proliferation, apoptosis, invasion, and metastasis. In this study, we describe the identification and molecular cloning of eight novel transcripts of the human KLK10 gene using 3′ rapid amplification of cDNA ends (3′ RACE) and next-generation sequencing (NGS), as well as their expression analysis in a wide panel of cell lines, originating from several distinct cancerous and normal tissues. Bioinformatic analysis revealed that the novel KLK10 transcripts contain new alternative splicing events between already annotated exons as well as novel exons. In addition, investigation of their expression profile in a wide panel of cell lines was performed with nested RT-PCR using variant-specific pairs of primers. Since many KLK mRNA transcripts possess clinical value, these newly discovered alternatively spliced KLK10 transcripts appear as new potential biomarkers for diagnostic and/or prognostic purposes or as targets for therapeutic strategies. - Highlights: • NGS was used to identify novel transcripts of the human KLK10 gene. • 8 novel KLK10 transcripts were identified. • A novel 3′UTR was detected and characterized. • The expression profiles of all 8 novel KLK10 transcripts were identified.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Upregulation of SOX2 activated LncRNA PVT1 expression promotes breast cancer cell growth and invasion

Increasing evidences indicated that Long noncoding RNAs (lncRNAs) played pivotal roles during tumorigenesis in multiple types of cancers, including breast cancer. This study aimed to investigate the role and function of long noncoding RNA PVT1 in the progression of breast cancer and explore the transcription factor which contributes to the regulation of PVT1 in breast cancer. Our results indicated that the expression of PVT1 was significantly upregulated in breast cancer tissues, compared with adjacent normal tissues (ANTs). And the increasing expression of PVT1 was associated with clinical stage, lymph nodes metastasis, and overall survival in breast cancer patients. Using computational screening, a transcriptional factor binding site was found between SOX2 and PVT1 promoter and the interaction between each other was further verified by chromatin immunoprecipitation (ChIP) analysis. In addition, ectopically overexpression of SOX2 can enhance breast cancer cell proliferation and invasion, while knockdown of SOX2 or PVT1 can severely attenuate this effect both in epithelial and mesenchymal types of breast cancer cells. Further evidences confirmed that overexpression of SOX2 can promote breast cancer cell EMT process; while silencing SOX2 or PVT1 expression can undermine this effect. These data suggest that elevated expression of SOX2 can activate lncRNA PVT1 expression promoted breast cancer tumorigenesis and progression. PVT1 may be a prognostic predictive biomarker for breast cancer, and the interaction of PVT1-SOX2 could be a therapeutic target in breast cancer. - Highlights: • SOX2 can bind to the promoter of LncRNA PVT1 and promotes it transcription in breast cancer cells. • Overexpression of SOX2 can activate PVT1 expression promote breast cancer cell growth and invasion. • PVT1 might be a prognostic biomarker in breast cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

TRIP6 promotes cell proliferation in hepatocellular carcinoma via suppression of FOXO3a

Highlights: • TRIP6 was upregulated in HCC cells and tissue. • TRIP6 expression was correlated with HCC patients’ clinical stage and poor survival. • TRIP6 enhanced the proliferation of HCC cells via suppression of FOXO3a. • TRIP6 may serve as a novel prognostic biomarker and therapeutic target in HCC. Thyroid hormone receptor-interacting protein 6 (TRIP6), a member of LIM family, acts as an adaptor protein and is overexpressed in several tumor types. However, the clinical significance and biological role of TRIP6 in HCC remains unknown. In our study, we found that TRIP6 was markedly overexpressed in HCC cells and clinical specimens compared with normal hepatocytes and adjacent non-tumor tissues. Immunohistochemical and statistical analysis showed that the expression of TRIP6 significantly correlated with HCC patients' clinical stage and poor survival. Moreover, we demonstrated that overexpressing TRIP6 significantly enhanced, whereas silencing endogenous TRIP6 inhibited, the proliferation and the anchorage-independent growth ability of HCC cells. In addition, overexpression of TRIP6 accelerated, while inhibition of TRIP6 retarded, G1-S phase transition in HCC cells. We further found that overexpression of TRIP6 increased the activation of AKT and suppressed the transactivity of FOXO3a. Meanwhile, overexpression of TRIP6 leaded to the decreased expression of cyclin-dependent kinase inhibitors p21{sup Cip1} and p27{sup Kip1} and increased expression of the cell cycle regulator cyclin D1. While silencing TRIP6 triggered the opposite effect. Taken together, these findings showed that TRIP6 plays an important role in promoting HCC cells proliferation and may serve as a novel prognostic biomarker and therapeutic target in HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Knockdown of long non-coding RNA MAP3K20 antisense RNA 1 inhibits gastric cancer growth through epigenetically regulating miR-375

Highlights: • lncRNA MLK7-AS1 is an independent prognostic factor for gastric cancer patients. • Knockdown of MLK7-AS1 inhibits gastric cancer cell growth. • MLK7-AS1 negatively and epigenetically controls miR-375 expression. Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis of gastric cancer. LncRNA MAP3K20 antisense RNA 1 (MLK7-AS1) has been identified as one of gastric cancer-specific lncRNAs. However, its precise role in gastric cancer remains unknown. In this study, we found that lncRNA MLK7-AS1 was significantly increased in gastric cancer tissues compared with in adjacent tissues. Gastric cancer patients with high MLK7-AS1 expression had a shorter survival and poorer prognosis. By loss-function assay, we demonstrated that knockdown of MLK7-AS1 inhibited cell proliferation and induced apoptosis in HGC27and MKN-45 cells. Furthermore, we identified miR-375 as a target of MLK7-AS1. MLK7-AS1 interacted with Dnmt1 and recruited it to miR-375 promotor, hyper-methylating miR-375 promotor and repressing miR-375 expression. Taken together, our findings demonstrate that knockdown of MLK7-AS1 by siRNA inhibits gastric cancer growth by epigenetically regulating miR-375. Thus, MLK7-AS1 may be a useful prognostic marker and therapeutic target for gastric cancer patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Methylation-induced silencing of SPG20 facilitates gastric cancer cell proliferation by activating the EGFR/MAPK pathway

Highlights: • Methylation-induced SPG20 silence facilitates gastric carcinogenesis. • SPG20 silencing induces cell proliferation by activating EGFR/MAPK signaling pathway. • The nomogram based on spartin provided survival prediction of gastric cancer. Spastic paraplegia 20 methylation was characterized in gastric cancer in our previous study. However, its mechanism remains unknown. Cell proliferation, colony formation, flow cytometry, wound healing, in vitro Transwell assays and in vivo xenografts were performed. A nomogram model was established to make a more accurate prognostic prediction for gastric cancer patients. Knockout of Spastic paraplegia 20 promoted gastric cancer cell proliferation, G2/M arrest in vitro and tumor growth in vivo. The EGFR/MAPK pathway was activated as a consequence of Spastic paraplegia 20 deletion. EGFR kinase or ERK1/2 inhibitors impaired Spastic paraplegia 20 knockout-induced cancer cell growth. Gastric cancer patients with poor spartin expression (72/161, 44.7%) exhibited a worse prognosis compared with the high expression group with median survival times of 16 and 54 months, respectively. The nomogram model stratified gastric cancer patients into 3 distinct prognostic groups with 3-year survival rates of 100%, 77%, and 35%. Furthermore, it had a better discrimination than the TNM staging system (C index: 0.785, AIC: 752.8708 VS. C index: 0.712; AIC: 775.1223). Methylation-induced Spastic paraplegia 20 silencing facilitates gastric cancer cell proliferation by activating the EGFR/MAPK signaling pathway. The nomogram based on spartin expression provided significantly better discrimination compared with the traditional AJCC TNM staging system and provided an individualized prediction of the survival for gastric cancer patient survival.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MiR-150 predicts survival in patients with sepsis and inhibits LPS-induced inflammatory factors and apoptosis by targeting NF-κB1 in human umbilical vein endothelial cells

Highlights: • Plasma miR-150 level is reduced in patients with sepsis. • Plasma miR-150 has a diagnostic and prognostic value in septic patients. • MiR-150 protects HUVECs from LPS-induced inflammatory injury. • NF-κB1 is a direct target of miR-150. MiR-150 is involved into some pathological processes, such as tumorigenesis and autoimmune diseases. However, little is known about the involvement of miR-150 in human sepsis. In this study, plasma miR-150 level had a diagnostic and independent prognostic value in patients with sepsis, and negatively correlated with renal dysfunction and 28-day survival as well as plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). MiR-150 expression was also significantly decreased in human umbilical vein endothelial cells (HUVECs) and C57BL/6 mice with sepsis after lipopolysaccharides (LPS) treatment. In-vitro, miR-150 over-expression protected HUVECs from LPS-induced apoptosis and the expressions of nuclear factor-κB1 (NF-κB1), IL-6, TNF-α, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Furthermore, NF-κB1 was identified as a direct target of miR-150. Restored NF-κB1 expression antagonized the protective effects of miR-150, while suppression of NF-κB1 enhanced these protective effects. Our findings indicate miR-150 predicts survival in patients with sepsis and inhibits LPS-induced inflammatory factors and apoptosis by targeting NF-κB1 in human umbilical vein endothelial cells. Thus, miR-150 may be a useful biomarker or target in the diagnosis, prognosis and treatment of patients with sepsis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Neutrophils infiltrating pancreatic ductal adenocarcinoma indicate higher malignancy and worse prognosis

Highlights: • Previous studies have reported that inflammation and peroxides may promote development of pancreatic ductal adenocarcinoma (PDAC). • Neutrophils, as inflammatory cells, can produce or peroxides in the stroma of cancer. . • It is difficult to investigate the interaction between neutrophils and PDAC cells. Here, CD177 was used to show distribution of neutrophils. • Expression of CD177 was negatively correlated with overall survival of patients. This phenomenon was observed from pathological specimens. • Therefore, we speculate that neutrophils infiltration is a negative prognostic factor for PDAC. CD177 is considered to represent neutrophils. We analyzed mRNA expression level of CD177 and clinical follow-up survey of PDAC to estimate overall survival (OS) from Gene Expression Omnibus (GEO) dataset (GSE21501, containing samples from 102 PDAC patients) by R2 platform (http://r2.amc.nl). We also analyzed correlated genes of CD177 by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to predict the potential relationship between neutrophils and prognosis of PDAC. We then performed hematoxylin and eosin (H&E) staining and immunohistochemical staining of surgical specimens to verify infiltration of neutrophils in PDAC tissues. After analyzing mRNA expression data and clinical follow-up survey provided in the GEO dataset (GSE21501, containing samples from 102 PDAC patients) and clinicopathological data of 23 PDAC patients, we demonstrated that CD177 was correlated with poor prognosis. The univariate Kaplan–Meier survival analysis revealed that OS was inversely associated with increased expression of CD177 (P = 0.012). Expression of phosphodiesterase (PDE)4D was positively related to CD177 in gene correlation analysis (R = 0.413, P < 0.001) by R2 platform. H&E staining and immunohistochemistry of CD177 in 23 PDAC surgical samples showed accumulation of neutrophils in the stroma and blood vessels around the cancer cells. In addition, immunohistochemical staining showed that CD177 was highly expressed in the stroma and blood vessels around tumor tissues of PDAC, which was similar to H&E staining. Expression of CD177 can be used to represent infiltration of neutrophils, which may have potential prognostic value in PDAC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression

Highlights: • The prognostic value of m{sup 6}A methyltransferase and demethylase in lung cancer. • Differentially expressed FTO accounts for the aberrant m{sup 6}A modification in LUSC. • FTO acts as an oncogene in LUSC. • MZF1 mediates FTO regulation in LUSC. N{sup 6}-Methyladenosine (m{sup 6}A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m{sup 6}A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m{sup 6}A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m{sup 6}A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m{sup 6}A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m{sup 6}A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The E3 ubiquitin ligase RNF146 promotes colorectal cancer by activating the Wnt/β-catenin pathway via ubiquitination of Axin1

Highlights: • RNF146 is increased and correlated with poor prognosis in colorectal cancer. • RNF146 exerts oncogenic role in colorectal cancer. • RNF146 activates the Wnt/β-catenin signaling via ubiquitination of Axin1. The E3 ubiquitin ligase ring finger protein 146 (RNF146) has been implicated in tumor development. However, the role and clinical significance of RNF146 in colorectal cancer (CRC) remain unknown. In this study, we reported for the first time that RNF146 was upregulated in CRC tissues as well as in cell lines. Further, RNF146 expression was independent prognostic factor for poor outcome of CRC patients. RNF146 knockdown in cell lines inhibited cell growth, promoted cell apoptosis in vitro and suppressed colorectal tumor growth in vivo. Mechanistic investigations revealed that RNF146 exerted oncogenic role through ubiquitination of Axin1 to activate β-catenin signaling. In addition, RNF146 expression was positively correlated with β-catenin expression in CRC tissues. Collectively, our data suggest that RNF146 might function as a oncogene in human CRC, and represent a promising prognostic factor and a valuable therapeutic target for CRC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-181d-5p-FOXP1 feedback loop modulates the progression of osteosarcoma

MicroRNAs (miRNAs) are playing more and more fundamental roles in the progress of human cancers. miR-181d-5p has not been fully elucidated in human cancers. In this study, we aimed to investigate the biological function and mechanism of miR-181d-5p in osteosarcoma (OS). At first, the expression conditions of miR-181d-5p were identified in OS tissues and cell lines. Downregulation of miR-181d-5p was identified to be a significant prognostic factor for patients with OS. Using the bioinformatics analysis, the putative target mRNA (FOXP1) of miR-181d-5p was found out. Similarly, the expression conditions and prognostic value of FOXP1 were identified in OS. To validate the tumor suppressive role of miR-181d-5p in OS, gain or loss of function assays were carried out in OS cell lines. The results indicated the anti-oncogenic function of miR-181d-5p in OS. Subsequently, the oncogenic function of FOXP1 in OS was identified by functional assays. Rescue assays manifested that the oncogenic function of FOXP1 can be partially reversed by miR-181d-5p. Combining with the result of luciferase reporter assay, we confirmed that miR-181d-5p can act as a tumor suppressor in OS via targeting FOXP1. Further mechanism experiments revealed that FOXP1 can suppressed the transcription activity of miR-181d-5p by acting as a transcription inhibitor. In conclusion, our study revealed that miR-181d-5p-FOXP1 feedback loop modulates cell proliferation and metastasis in osteosarcoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

DDX5 promotes hepatocellular carcinoma tumorigenesis via Akt signaling pathway

The DEAD-box-protein DDX5 is an ATP-dependent RNA helicase and also acts as co-activator that contributes to progression and metastasis of various tumours. However, its expression as well as prognostic roles of DDX5 in hepatocellular carcinoma (HCC) remain elusive. In this study, we investigated clinical significance and biological functions of DDX5 in HCC. Our results suggested that DDX5 showed overexpression at both transcriptional and translational levels in HCC tissues compared with adjacent normal tissues. Moreover, DDX5 expression was demonstrated to be correlated with tumor size (p p = 0.013), M stage (p = 0.006), tumor differentiation (p p = 0.001). Simultaneously, high DDX5 expression was found to be significantly correlated to worse outcome including Disease free survival (DFS) (p = 0.016) and overall survival (OS) (p = 0.032) according to Kaplan-Meier survival analysis. In vitro studies, it suggested that knockdown of DDX5 suppressed HCC cells migration, invasion and epithelial -to- mesenchymal transition (EMT) process. Depletion of DDX5 could promote HCC cells growth. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that PI3K/Akt signaling pathway obtained the highest enrichment. Furthermore, we found that knockdown of DDX5 decreased Akt as well as p-Akt (S473) expressions. Collectively, these findings suggested that DDX5 facilitated HCC cells growth via Akt signaling pathway. DDX5 played a crucial role in HCC proliferation and tumorigenesis and may be a novel prognostic marker and potential therapeutic target for HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Platelet-derived growth factor receptor alpha (PDGFRα) is overexpressed in NK/T-cell lymphoma and mediates cell survival

Nasal-type natural killer/T-cell lymphoma (NKTCL) is a subtype of non-Hodgkin lymphoma (NHL) that is clinically aggressive and has a poor prognosis. Platelet-derived growth factor receptors (PDGFRs) and their ligands (PDGFs) play important roles in angiogenesis, cancer cell proliferation, survival, migration and poor prognosis in various tumours. However, the significance of PDGFRs in NKTCL remains unknown. Herein, the present study aimed to investigate the important role of PDGFRα in pathogenesis, progression and prognisis of NKTCL. Firstly, we performed immunohistochemical staining, qRT-PCR and western blotting to determine PDGFRα expression in formalin-fixed, paraffin-embedded tissue sections from 78 NKTCL cases and in cell lines. Secondly, correlations between PDGFRα expression and NKTCL clinical parameters and prognosis were analysed. Moreover, a biological assessment of PDGFRα blockade in two NKTCL cell lines was conducted through proliferation assay, cell-cycle evaluation and apoptosis detection by flow cytometry analyses. Furthermore, we detected in vivo activity of imatinib in mouse model of NKTCL. We found that the expression of PDGFRα was significantly higher in NKTCL tissues compared to the reactive lymphoid hyperplasia of the nasopharynx (P = 0.028). High PDGFRα expression was strongly associated with a high LDH level (P = 0.028) and III-IV stage (P = 0.013). NKTCL patients with high PDGFRα expression displayed a reduced median overall survival time and progression-free survival time when compared with those with low PDGFRα expression (P = 0.011, P = 0.005, respectively). Cox multivariate analysis showed that III-IV stage (P = 0.024) and high PDGFRα expression (P = 0.003) were independent prognostic factors in NKTCL patients. Biological assessment assays in two NKTCL cell lines revealed that a specific PDGFR antagonist, imatinib, inhibited cell viability, blocked cell cycle progression at G0/G1 stage and induced apoptosis. Similarly, the in vivo assay showed that imatinib delayed mouse model tumour growth. In conclusion, NKTCL tumour cells have prominent PDGFRα expression, which can serve as a candidate prognostic marker. PDGFR antagonists have significant biological effect on NKTCL and may be useful therapeutic agents for treatment of NKTCL.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Downregulated miR-1247-5p associates with poor prognosis and facilitates tumor cell growth via DVL1/Wnt/β-catenin signaling in breast cancer

The abnormal expression of microRNAs is a key hallmark of breast cancer. Nevertheless, the biological roles of miR-1247-5p in breast cancer remain unknown. In this study, we revealed that miR-1247-5p expression was markedly decreased in breast cancer. It was a valuable diagnostic biomarker for breast cancer with the area under the curve of more than 0.80. Reduced miR-1247-5p expression was significantly correlated with patient age, tumor size, and poor prognosis in The Cancer Genome Atlas cohort including 839 breast cancer patients. Multivariate Cox regression analysis demonstrated that miR-1247-5p was an independent prognostic indicator for overall survival (hazard radio [HR] = 1.683, 95% confidence interval [CI] = 1.087–2.606, p = 0.020) and recurrence-free survival (HR = 2.496, 95% CI = 1.576–3.951, p < 0.001). Moreover, functional studies showed that overexpression of miR-1247-5p inhibited proliferation and induced apoptosis in breast cancer cells. Bioinformatics analysis and mechanistic investigations revealed that Dishevelled 1 (DVL1) was a direct target of miR-1247-5p. Inhibition of DVL1 by miR-1247-5p resulted in the suppression of Wnt/β-catenin signaling, whereas overexpression of DVL1 abrogated the miR-1247-5p-mediated effect. These data reveal that miR-1247-5p, as an oncosuppressor in breast cancer, may be a promising prognostic biomarker and therapeutic target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

FAT10 promotes the invasion and migration of breast cancer cell through stabilization of ZEB2

Highlights: • High FAT10 level was closely associated with the malignant phenotype and shorter survival in the BC patients. • FAT10 knockdown suppressed the metastasis abilities and the EMT of breast cancer cell. • FAT10 directly interacts with ZEB2 and stabilizes its expression in breast cancer cells. • The pro-metastasis role of FAT10 in breast cancer is dependent on ZEB2 enhancement. FAT10, an ubiquitin-like protein, functions as a potential tumor promoter in several caners. However, the function and clinical significance of FAT10 in breast cancer (BC) remains unclear. Here, we found that high FAT10 expression was detected frequently in primary BC tissues, and was closely associated with malignant phenotype and shorter survival among the BC patients. Multivariate analyses also revealed that FAT10 overexpression was independent prognostic factors for poor outcome of patients with BC. Function assay demonstrated that FAT10 knockdown significantly inhibited the metastasis abilities and the epithelial-mesenchymal transition (EMT) of breast cancer cell. Further investigation revealed that FAT10 directly bound ZEB2 and decreased its ubiquitination to enhance the protein stability of ZEB2 in BC cells. Moreover, our data shown that the pro-metastasis effect of FAT10 in BC is partially dependent on ZEB2 enhancement. Collectively, our data suggest that FAT10 plays a crucial oncogenic role in BC metastasis, and we provide a novel evidence that FAT10 may be serve as a prognostic and therapeutic target for BC patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Forecasting battery capacity and power degradation with multi-task learning

Lithium-ion batteries degrade due to usage and exposure to environmental conditions, which affects their capability to store energy and supply power. Accurately predicting the capacity and power fade of lithium-ion battery cells is challenging due to intrinsic manufacturing variances and coupled nonlinear ageing mechanisms. In this paper, we propose a data-driven prognostics framework to predict both capacity and power fade simultaneously with multi-task learning. The model is able to predict the degradation trajectory of both capacity and internal resistance together with knee-points and end-of-life points accurately at early-life stage. The validation shows an average percentage error of 2.37% and 1.24% for the prediction of capacity fade and resistance rise, respectively. The model's ability to accurately predict the degradation, facing capacity and resistance estimation errors, further demonstrates the model's robustness and generalizability. Compared with single-task learning models for forecasting capacity and power degradation, the model shows a significant prediction accuracy improvement and computational cost reduction. This work presents the highlights of multi-task learning in the degradation prognostics for lithium-ion batteries.

25 ENERGY STORAGE↗