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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 919 records · Page 51
All sourcesNASA NTRSDOE OSTI
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

Androgen-responsive circular RNA circSMARCA5 is up-regulated and promotes cell proliferation in prostate cancer

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males worldwide. Circular RNA (circRNA) is a unique class of RNA transcribed by RNA polymerase II characterized by jointing 3′ and 5′ ends together via exon or intron circularization. However, the molecular functions of circRNAs in prostate cancer have rarely been explored. In present study, we found circ-SMARCA5 was up-regulated in prostate cancer samples compared to match normal tissues. We also observed circ-SMARCA5 expression was significantly induced after DHT treatment. Functional experiments showed circ-SMARCA5 acted as an oncogene in prostate cancer by promoting cell cycle and inhibiting cell apoptosis. We thought this study provided useful information for exploring circRNAs as potential therapeutic and prognostic targets for prostate cancer. - Highlights: • To our knowledge, this is the first study to explore the molecular functions of circRNA in prostate cancer. • Our study showed that circ-SMARCA5 promoted cell proliferation and inhibited cell apoptosis in prostate cancer. • circ-SMARCA5 was for the first time reported as an androgen-responsive circRNA. • circ-SMARCA5 was for the first time reported to be up-regulated in prostate cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level

The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27. SOC cells with COPS5 depletion were arrested in G1/G0-phase and exhibited a reduced proliferation ability and an increased cytoplasmic p27 expression. Whereas, the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3. Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC. - Highlights: • As a negative regulator of p27, COPS5 depression could inhibits the proliferation of serous ovarian cancer cells. • Knockdown of COPS5 resulted in the maintaining duration of the G1-phase accompanied by cytoplasm localization of p27. • Either inhibitor CSN5i-3 or COPS6 knockdown would result in COPS5 suppression and p27-mediated S arrest. • COPS5 suppression promotes the activity osf Akst and sensitizes SOC cells to MK2206.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

The NAMPT/E2F2/SIRT1 axis promotes proliferation and inhibits p53-dependent apoptosis in human melanoma cells

Melanoma is the most common primary malignant neoplasm in adults, causing more deaths than any other skin cancer, necessitating the development of new target-based approaches. Current evidence suggests SIRT1, the mammalian nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting NAD{sup +} biosynthetic enzyme, together comprise a novel systemic regulatory network to play a pivotal role in cell proliferation and apoptosis. Nevertheless, how the regulation of this cofactor interfaces with signal transduction network remains poorly understood in melanoma. Here, we report NAMPT is highly expressed in melanomaassociated with poor overall survival in patients. Pharmacological and genetic inhibition of NAMPT decreased NAD{sup +} levels and melanoma cell proliferation capacity, and NAMPT knockdown induced apoptosis through the activity of the tumor suppressor p53. Next, we demonstrate NAMPT regulates the transcription factor E2F family member 2 (E2F2) in the apoptosis process. Downstream, E2F2 control the mRNA and protein levels of SIRT1. Finally, we find NAMPT mediates the apoptosis resistance of melanoma cells through NAMPT-E2F2-SIRT1 axis, more than NAD{sup +}-driven transcriptional program. Accordingly, our results demonstrated that NAMPT is a prognostic marker in melanoma, and the identificationofNAMPT-E2F2-SIRT1 pathway establishes another link between NAMPT and apoptosis events in melanoma, with therapeutic implications for this deadly cancer. - Highlights: • The expression of NAMPT is remarkably high in melanoma tumors and associated with poor overall survival in patients. • NAMPT is required for E2F2 and SIRT1 expression for regulating p53 and apoptosis levels in human melanoma cells. • NAMPT/E2F2/SIRT1 is a novel regulatory pathway that governs melanoma cells proliferation and apoptosis resistance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

High expression of Ki-67 acts a poor prognosis indicator in locally advanced nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy in Southern China and Southeast Asia compared with Western countries. The standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to satisfactory treatment, it can cause local recurrence and distant metastases in some patients after treatment by radiation. We retrospectively reviewed 108 NPC patients (7th AJCC Ⅲ-Ⅳa) who have received intensity modulated radiation therapy (IMRT) between August 2008 and January 2012 at Xiangya Hospital of Central South University. Ninety-eight patients with >60% reduction of tumor size after radiation treatment were regarded as radiation sensitive, Ten patients with <40% reduction of tumor size after radiation treatment were regarded as radiation resistant. Using immunohistochemistry, we found that the high expression rate of Ki-67 in radiation resistant and radiation sensitive patients was 80.0% and 42.6%, respectively, and the difference was statistically significant (p = 0.025). The 5-year progress free survival rates in patients with low and high expression of Ki-67 was 70.7% and 48.0%, respectively, and the difference was statistically significant (p = 0.0008). Multivariate Cox regression analysis identified that high expression of Ki-67 was an independent negative prognostic factor in nasopharyngeal carcinoma patients [Hazard ratio (95% CI), 2.098(1.101, 3.996); p = 0.024]. These results demonstrate that high expression of Ki-67 contributes to radiation resistance and acts a poor prognosis indicator in patients with locally advanced nasopharyngeal carcinoma. - Highlights: • Radiation resistance remains a serious obstacle in some locally advanced nasopharyngeal carcinoma patients after treatment by radiation. • The proportion of Ki67 + cells after radiotherapy provided an independent variable of responsiveness to radiotherapy in squamous cell carcinoma of the head and neck. • The expression of Ki67 association with radiation resistance in locally advanced nasopharyngeal carcinoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Overexpression of DBC1, correlated with poor prognosis, is a potential therapeutic target for hepatocellular carcinoma

Highlights: • DBC1 was upregulated in HCC tissues and cell lines. • Overexpression of DBC1 was correlated with clinicopathological parameters in HCC. • Overexpression of DBC1 predicts poor disease-free survival (DFS) and overall survival (OS) in HCC. • Knockdown of DBC1 inhibits HCC cell lines proliferation. Deleted in Breast Cancer 1 (DBC1) is a regulatory protein involved in cell metabolism and cancer progression. Nevertheless, the expression and prognostic values of DBC1 in hepatocellular carcinoma (HCC) are still not well understood. The following study investigated the clinical significance and biological function of DBC1 in HCC. Briefly, overexpression of DBC1 at transcriptional and translational levels in human HCC tissues compared to adjacent normal tissues was observed using quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB) and immunohistochemistry (IHC) approach. Furthermore, upregulated DBC1 was significantly correlated with tumor size (p = 0.005), N stage (p = 0.016), M stage (p = 0.011), tumor differentiation (p in vitro. To conclude, these findings demonstrated that DBC1 was essential in tumorigenesis and proliferation. Moreover, it was identified as a potential therapeutic target for HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Inhibition of CIP2A attenuates tumor progression by inducing cell cycle arrest and promoting cellular senescence in hepatocellular carcinoma

Highlights: • High expression level of CIP2A was frequently observed in hepatocellular carcinoma (HCC). • CIP2A expression level was associated with unfavorable overall and recurrence-free survival in HCC patients. • Inhibition of CIP2A attenuated HCC progression via inducing cell cycle arrest and promoting cellular senescence. CIP2A is a recent identified oncogene that inhibits protein phosphatase 2A (PP2A) and stabilizes c-Myc in cancer cells. To investigate the potential oncogenic role and prognostic value of CIP2A, we comprehensively analyzed the CIP2A expression levels in pan-cancer and observed high expression level of CIP2A in majority cancer types, including hepatocellular carcinoma (HCC). Based on a validation cohort including 60 HCC and 20 non-tumorous tissue samples, we further confirmed the high mRNA and protein expression levels of CIP2A in HCC, and found high CIP2A mRNA expression level was associated with unfavorable overall and recurrence-free survival in patients with HCC. Mechanistic investigations revealed that inhibition of CIP2A significantly attenuated cellular proliferation in vitro and tumourigenicity in vivo. Bioinformatic analysis suggested that CIP2A might be involved in regulating cell cycle. Our experimental data further confirmed CIP2A knockdown induced cell cycle arrest at G1 phase. We found accumulated cellular senescence in HCC cells with CIP2A knockdown, companying expression changes of senescence associated proteins (p21, CDK2, CDK4, cyclin D1, MCM7 and FoxM1). Mechanistically, CIP2A knockdown repressed FoxM1 expression and induced FoxM1 dephosphorylation. Moreover, inhibition of PP2A by phosphatase inhibitor rescued the repression of FoxM1. Taken together, our results showed that CIP2A was highly expressed in HCC. Inhibition of CIP2A induced cell cycle arrest and promoted cellular senescence via repressing FoxM1 transcriptional activity, suggesting a potential anti-cancer target for patients with HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Downregulation of Nedd4L predicts poor prognosis, promotes tumor growth and inhibits MAPK/ERK signal pathway in hepatocellular carcinoma

Highlights: • Nedd4L is down-regulated in HCC tissues. • Downregulation of Nedd4L predicts poor prognosis of HCC. • Nedd4L inhibits the proliferation of HCC in vitro and in vivo. • Nedd4L phosphorylates ERK1/2 and regulates genes related with apoptosis. Accumulating evidence indicates that the neural precursor cell–expressed, developmentally downregulated 4–like (Nedd4L) related with some tumor progression pathways and was found abnormally expressed in several kinds of solid cancers. However, the role and mechanism of Nedd4L in HCC remain unknown. This study was to assess the role of Nedd4L in HCC tumorigenesis and prognosis. The real-time quantitative RT-PCR and immunohistochemistry results revealed that Nedd4L was downregulated in HCC tissues compared to corresponding peri-noncancerous tissue, and HCC patients with low expression of Nedd4L exhibited poor prognosis assessed by Kaplan-Meier and Cox regression analysis in 78 HCC patients. Furthermore, knockdown of Nedd4L could significantly promote proliferation of HCC cells by CCK-8 and colony formation assays in vitro; whereas ectopic expression of Nedd4L resulted in attenuating proliferation in vitro and tumor growth in vivc determined by nude mice xenografts model. Mechanically, Nedd4L could phosphorylate ERK1/2 and regulate genes related with apoptosis. Collectively, Nedd4L plays a tumor suppressive role in HCC, possibly through triggering MAPK/ERK-mediated apoptosis, and Nedd4L downregulation may be a potential prognostic biomarker as well as a therapeutic target for HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Hypothesis: Hypoxia induces de novo synthesis of NeuGc gangliosides in humans through CMAH domain substitute

Highlights: • In humans, the key enzyme for NeuGc synthesis, CMAH, is non-functional. • The presence of NeuGc gangliosides in human cancer cells represents an enigma. • We tested the effect of hypoxia by stable isotope labeling in cell culture (SILAC). • Subunit B of respiratory complex II (SDHB) was found upregulated. • Could CMAH be substituted by SDHB, another [Fe{sub 2}S{sub 2}]-containing domain? Immunotherapy is a growing field in cancer research. A privileged tumor-associated antigen that has received much attention is N-glycolyl (NeuGc) GM3. This ganglioside is present in several types of cancer, but is almost undetectable in human healthy tissues. However, its non-hydroxylated variant, NeuAc GM3, is abundant in all mammals. Due to a deletion in the human gene encoding the key enzyme for synthesis of NeuGc, humans, in contrast to other mammals, cannot synthesize NeuGc GM3. Therefore the presence of this ganglioside in human cancer cells represents an enigma. It has been shown that hypoxic conditions trigger the expression of NeuGc gangliosides, which not only serve as attractive targets for cancer therapy, but also as diagnostic and prognostic tumor marker. Here, we confirm hypoxia-induced expression of the NeuGc GM3 ganglioside also in HeLa cells and reveal several candidate proteins, in particular GM3 synthase and subunit B of respiratory complex II (SDHB), that may be involved in the generation of NeuGc GM3 by SILAC-based proteome analysis. These findings have the potential to significantly advance our understanding of how this enigmatic tumor-associated antigen is produced in humans, and also suggest a possible mechanism of action of anti-tumor antibodies that recognize hypoxia markers, such as 14F7.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Apatinib inhibits migration and invasion as well as PD-L1 expression in osteosarcoma by targeting STAT3

Highlights: • The expression patterns and prognostic roles of VEGFR2 and PD-L1 in osteosarcoma are investigated. • Apatinib reduces the migration and invasion of osteosarcoma cells in vitro and in vivo. • Apatinib suppresses EMT and PD-L1 expression in osteosarcoma cells in vitro and in vivo. The cure rate of osteosarcoma has not improved in the past 30 years. The new treatments and drugs is urgently needed, especially for metastatic osteosarcoma. Anti-angiogenesis therapy and immunotherapy has got promising anti-tumor effects in various tumors. It is hypothesised that combining checkpoint inhibitor immunotherapies with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. However, its underlying mechanism remain largely uninvestigated. To investigate the clinical significance of vascular endothelial growth factor receptor-2 (VEGFR2) and programmed death ligand-1 (PD-L1) in osteosarcoma, we analyzes their expression levels in 93 osteosarcoma specimens by immunohistochemistry. Meanwhile, we analyzes their correlation with the metastatic behavior and overall survival (OS). We also investigate the effects of Apatinib on migration and invasion of osteosarcoma cells and its underlying mechanism in vitro and in vivo. In our study, the positive rates of the VEGFR2 and PD-L1 expression are 64.5% (60/93) and 35.5% (33/93), respectively. A significant correlation is detected between VEGFR2 and PD-L1 expression (P = 0.009). Receiver-operating characteristic (ROC) curves analysis indicates the predictive value of the two markers in tumor metastasis, and both PD-L1 and VEGFR2 are negatively correlated with OS. Transwell assays reveals that VEGFR2 inhibition attenuates migration and invasion of osteosarcoma cells. Mechanistically, we demonstrate that Apatinib attenuates migration and invasion by suppressing epithelial-mesenchymal transition (EMT) and inactivating STAT3. Additionally, Apatinib reduces PD-L1 expression in osteosarcoma cells. Apatinib markedly weakens pulmonary metastatic potential of osteosarcoma in vivo. In conclusion, our study reveals a pro-metastatic functional mechanism for VEGFR2 in osteosarcoma. Furthermore, we demonstrate that Apatinib exerts anti-tumor effect not only through antiangiogenic effect, but also via suppressing immune escape, which may represent a potential therapeutic target for metastatic osteosarcoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Upregulation of CDCA5 promotes gastric cancer malignant progression via influencing cyclin E1

Highlights: • Upregulation of CDCA5 correlates with more advanced clinical features and worse survival in gastric cancer patients. • Inhibition of CDCA5 suppresses gastric cancer cells proliferation in vitro and tumor growth in vivo. • CDCA5 promotes gastric cancer malignant progression via influencing cyclin E1 expression. The cell division cycle associated 5(CDCA5) was reported to be associated with progression of several human cancers, however, its clinical significance and biological role still remain unknown in gastric cancer(GC). By analyzing The Cancer Genome Atlas(TCGA), we found CDCA5 was significantly upregulated in GC tissues compared to adjacent normal tissues. Tissue microarray(TMA) indicated upregulation of CDCA5 was significantly correlated with more advanced clinicopathological features, and acts as an independent risk factor for worse overall survival(OS) in GC patients. Moreover, silence of CDCA5 suppresses proliferation of GC cells by inducing G1-phase arrest via downregulating Cyclin E1(CCNE1). Our results demonstrate upregulation of CDCA5 promotes GC malignant progression, which may offer a potential prognostic and therapeutic strategy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Analysis of T cell receptor repertoire in monozygotic twins concordant and discordant for chronic hepatitis B infection

Highlights: • TCR Repertoire features from twin pairs show heritable bias. • TCR repertoires show antigen biases in chronic viral infection patients. • TCR repertoires show a high level of concordance among HBeAg-positive HBV twins. • Shared clonotypes in identical cured twins show therapeutic potential. Due to their identical inheritance and shared surroundings, identical twins have been the recommended group for studying the susceptibility and prognosis of diseases. Here, CD8{sup +} T cell receptor beta (TCRβ) chains were analyzed by high-throughput sequencing in three pairs of healthy identical twins and chronic hepatitis B patients. The data showed a high level of similarity in the TCR repertoire of each pair in terms of average TCR Vβ segment expression and frequency of the complementary determining region 3 (CDR3) pattern and skewed or oligoclonal clonotypes. Notably, the level of similarity in TCR Vβ expression between the twins appeared to be independent of the consistency or inconsistency of chronic HBV infection, although the detailed CDR3 pattern and frequency were related to disease prognosis. There were more immunodominant clonotypes in patients with HBV antigen seroconversion, which showed an increased abundance. These immunodominant clonotypes may be used as favorable prognostic biomarkers and potential targets for immunotherapy. Thus, delineating the CD8{sup +} T cell repertoire of identical twins with concordant chronic viral infections provides a promising means to screen protective TCR genes for immunotherapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

TINCR facilitates non-small cell lung cancer progression through BRAF-activated MAPK pathway

Highlights: • TINCR facilitates NSCLC. • TINCR interacts with BRAF. • TINCR activates MAPK by BRAF. Long non-coding RNAs are critically involved in oncogenesis in various cancer types. Here we reported a novel lncRNA signature correlated with progression of non-small cell lung cancer (NSCLC). In particular, we identified elevated expression of terminal differentiation-induced noncoding RNA (TINCR) in human NSCLC samples, which were associated with enhanced migration, viability in NSCLC cells in vitro. Higher TINCR level was also correlated with poor survival. Furthermore, TINCR increased xenograft tumor growth in vivo mouse models. Mechanistic study demonstrated that TINCR can interact with BRAF to facilitate its kinase activity, thereby leading to activation of oncogenic mitogen-activated protein kinase (MAPK) pathway. These results suggested that TINCR upregulation may signal through the MAPK pathway to promote NSCLC tumorigenesis. Therefore, TINCR may serve as a potential prognostic marker and therapeutic target for NSCLC patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-126-5p targets Malate Dehydrogenase 1 in non-small cell lung carcinomas

Highlights: • A microRNA (miR) screen identified 3 binding sites of miR-126-5p in the 3′UTR of MDH1. • miR-126 and MDH1 are inversely correlated in large primary cohorts of NSCLCs. • miR-126 can reduce the protein level of MDH1, while sparing its isoenzyme MDH2. • miR-126-5p inhibits the MDH1 enzymatic activity and mitochondrial respiration. • miR-126-5p exerts cytostatic and cytotoxic effects in NSCLCs. Malate Dehydrogenase (MDH) 1 has recently been shown to be highly expressed and display prognostic value in non-small cell lung carcinomas (NSCLCs). However, it is not known how MDH1 expression is regulated and there is no current molecular or chemical strategy that specifically targets MDH1. This may be due to structural and enzymatic similarities with its isoenzyme, malate dehydrogenase 2 (MDH2). However, MDH1 and MDH2 are encoded by distinct genes and this opens up the possibility for modulation at the expression level. Here, we screened in silico for microRNAs (miRs) that selectively targets the 3′UTR region of MDH1. These analyses revealed that mir-126-5p has three binding sites in the 3′UTR region of MDH1. Additionally, we show that expression of miR-126-5p suppresses the enzymatic activity of MDH1, mitochondrial respiration and caused cell death in NSCLC cell lines.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Oncogenic MicroRNA-20a is downregulated by the HIF-1α/c-MYC pathway in IDH1 R132H-mutant glioma

Highlights: • MiR-20a is down-regulated in IDH1 R132H mutant-glioma. • IDH1 R132H mutation attenuates miR-20a expression via HIF-1α/c-MYC pathway. • The downregulated miR-20a contributes to the therapeutic sensitivity of IDH1 mutant gliomas. Mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been identified as one of the earliest events in gliomagenesis, occurring in over 70% of low grade gliomas and are present in the vast majority of secondary glioblastoma (GBM) that develop from these low-grade lesions. The aim of this study was to investigate whether the IDH1 R132H mutation influences the expression of oncogenic miR-20a and shed light on the underlying molecular mechanisms. The findings of the current study demonstrate presence of the IDH1 R132H mutation in primary human glioblastoma cell lines with upregulated HIF-1α expression, downregulating c-MYC activity and resulting in a consequential decrease in miR-20a, which is responsible for cell proliferation and resistance to standard temozolomide treatment. Elucidating the mechanism of oncogenic miR-20a activity introduces its role among well-established signaling pathways (i.e. HIF/c-MYC) and may be a meaningful prognostic biomarker or target for novel therapies among patients with IDH1-mutant glioma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types

Highlights: • Blood were collected from gastric, colorectal, lung, breast, prostate cancer patients. • PD-L1 expression was detected in the plasma at varying frequencies. • No PD-L1 mRNA was detected in cancer-free individuals. • PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types. Tumors inhibit antitumor response by modulating the immune checkpoint proteins programmed death ligand 1 (PD-L1) and its cognate receptor PD1. The expression of these genes has been implicated in evasion of immune response and resistance to targeted therapies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Silencing LncRNA LOXL1-AS1 attenuates mesenchymal characteristics of glioblastoma via NF-κB pathway

Highlights: • LncRNA LOXL1-AS1 expression is increased in mesenchymal subtype of GBM. • Knocking down LOXL1-AS1 could suppresse GBM cell proliferation. • Silencing LncRNA LOXL1-AS1 Attenuates Mesenchymal Characteristics of Glioblastoma via reducing NF-κB transcription activity. The mesenchymal (MES) subtype of glioblastoma (GBM) suggested worse prognosis and a more malignant phenotype in comparison with their proneural (PN) counterpart. The plasticity between PN and MES transcriptome signatures provided clinical intervention with an manner. Few LncRNA, however, have been discovered to take part in the shift between subtypes. Here, we used transcriptomic data and experimental evidences to demonstrate that silencing LncRNA LOXL1-AS1 was a new regulator of NF-κB signaling pathway through repressing RELB directly, resulting in increased marker genes of PN subtype and decreased those of MES.GBM cell proliferation was functionally suppressed by LOXL1-AS1's knockdown expression,. Furthermore, RELB's rescue could reverse LOXL1-AS1's effects partially in GBM malignant behaviors. LOXL1-AS1 could clinically serve as a poor prognostic indicator for GBM patients. In conclusion, our results suggest that LOXL1-AS1 contributes to aggressive biological processes that are related with MES phenotype via NF-κB signaling, which expand our perceptions into the underlying mechanisms in LOXL1-AS1-based and subtype transition adapted medicine for GBM management.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA hsa{sub c}ircRNA{sub 1}03809 promotes lung cancer progression via facilitating ZNF121-dependent MYC expression by sequestering miR-4302

Lung cancer characterized with malignant cell growth is the leading cause of cancer-related deaths. In recent years, several circular RNAs (circRNAs) have been reported to participate in lung cancer progression. However, the correlation between circular RNA (circRNA) and lung cancer still remains to be further investigated. In this study, we screened out a highly expressed circular RNA hsa{sub c}ircRNA{sub 1}03809 in lung cancer tissues. We showed hsa{sub c}ircRNA{sub 1}03809 could serve as a prognostic biomarker for patients with lung cancer. Furthermore, we found that hsa{sub c}ircRNA{sub 1}03809 knockdown significantly suppressed lung cancer cell proliferation and invasion in vitro and delayed tumor growth in vivo. In mechanism, we identified hsa{sub c}ircRNA{sub 1}03809 as a sponge of miR-4302 targeting ZNF121. By sequestering miR-4302, hsa{sub c}ircRNA{sub 1}03809 promoted the expression of ZNF121 which consequently enhanced MYC protein level in lung cancer cells. Through rescue assays, we demonstrated hsa{sub c}ircRNA{sub 1}03809 contributed to lung cancer cell proliferation and invasion via facilitating ZNF121-dependent MYC expression by sponging miR-4302. In conclusion, our findings illustrated a novel hsa{sub c}ircRNA{sub 1}03809/miR-4302/ZNF121/MYC regulatory signaling pathway in lung cancer progression.

60 APPLIED LIFE SCIENCES↗