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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 883 records · Page 49
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Loss of RapC causes defects in cytokinesis, cell migration, and multicellular development of Dictyostelium

Highlights: • We characterized the functions of RapC, an isoform of Rap1 small GTPase. • Loss of RapC causes defects in cytokinesis, cell migration, and development. • RapC plays a negative role in cell spreading and cell adhesion. • RapC is involved in tip formation from mounds during multicellular development. • This contributes to the understanding of Ras-mediated cellular processes. The small GTPase Ras proteins are involved in diverse cellular processes. We investigated the functions of RapC, one of 15 Ras subfamily GTPases in Dictyostelium. Loss of RapC resulted in a spread shape of cells; severe defects in cytokinesis leading to multinucleation; decrease of migration speed in chemoattractant-mediated cell migration, likely through increased cell adhesion; and aberrations in multicellular development producing abnormal multiple tips from one mound and multi-branched developmental structures. Defects in cells lacking RapC were rescued by expressing GFP-RapC in rapC null cells. Our results demonstrate that RapC, despite its high sequence homology with Rap1, plays a negative role in cell spreading and cell adhesion, in contrast to Rap1, which is a key regulator of cell adhesion and cytoskeleton rearrangement. In addition, RapC appears to have a unique function in multicellular development and is involved in tip formation from mounds. This study contributes to the understanding of Ras-mediated cellular processes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Cytoprotective role of ubiquitin against toxicity induced by polyglutamine-expanded aggregates

Highlights: • Formation of IBs composed of Q103 aggregates is independent of cellular Ub levels. • Ub deficiency is sufficient to cause the accumulation of Q103 aggregates in MEFs. • Ub deficiency leads to impaired autophagic clearance of Q103 aggregates in MEFs. • Ub-deficient MEFs are more susceptible to the toxicity caused by Q103 aggregates. Ubiquitin (Ub) homeostasis is important for cellular function and survival, especially under stress conditions. Recently, we have demonstrated that Ubc{sup −/−} (Ub-deficient) mouse embryonic fibroblasts (MEFs) exhibited reduced viability under oxidative stress induced by arsenite, which was not due to dysregulation of the antioxidant response pathway, but rather due to the potential toxicity caused by the misfolded protein aggregates. However, it is still not clear whether Ub deficiency is directly related to the accumulation of toxic protein aggregates, as arsenite itself triggers protein aggregation and renders cells into aberrant conditions such as reduced proteasome function and inhibition of autophagic flux. Therefore, under arsenite treatment, the outcome could be derived from the combination of multiple defective pathways. Furthermore, it has also been suggested that ubiquitination status of misfolded proteins may not be important for the formation of inclusion bodies composed of misfolded protein aggregates. We therefore wondered whether Ub deficiency is sufficient to trigger the accumulation of toxic protein aggregates inside the cells. In this study, we ectopically expressed polyQ-expanded aggregates (Q103) in MEFs and observed inclusion body formation at the juxtanuclear region, which was independent of cellular Ub levels. In contrast to arsenite treatment, polyQ expression did not affect proteasome function. However, we observed an increased accumulation of Q103 aggregates in Ubc{sup −/−} MEFs, which was due to impaired autophagic clearance. Finally, we demonstrated that the increased accumulation of Q103 aggregates under Ub deficiency dramatically reduced the viability of cells. Therefore, our results suggest that the maintenance of proper levels of cellular Ub is important to protect cells against the toxicity induced by the accumulation of protein aggregates.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Small nucleolar RNA U2{sub 1}9 promotes hepatocellular carcinoma progression by regulating Wnt/β-catenin signaling

Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have malfunctioning roles in oncogenesis. In the present study, we investigated the role of box C/D small nucleolar RNA U2{sub 1}9 (snoU2{sub 1}9) in the tumorigenesis of hepatocellular carcinoma (HCC). Recently, we screened snoRNAs differential signatures by performing high-throughput small RNA sequence in HCC tissues and validated that upregulated snoU2{sub 1}9 was associated with aggressive phenotypes in HCC patients. Aberrant snoU2{sub 1}9 facilitated HCC cell proliferation, inhibited apoptosis and induced cell cycle progression in vitro analyses. We globally investigated the molecular mechanisms of snoU2{sub 1}9 in HCC and found that snoU2{sub 1}9 knockdown inhibited Wnt/β-catenin signaling pathway through inducing the translocation of β-catenin in cytoplasm. We concluded that snoU2{sub 1}9 plays a pathological role in the development and progression of HCC, and is a potential therapeutic target for HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LincRNA-RoR/miR-145 promote invasion and metastasis in triple-negative breast cancer via targeting MUC1

Highlights: • LincRNA-ROR was upregulated in TNBC cell lines and tissue samples. • LincRNA-ROR was able to significantly promote the invasion and metastasis of TNBC cell lines MDA-MB-231. • LincRNA-ROR/miR-145 regulated invasion and metastasis of MDA-MB-231 via the target MUC1. Triple-negative breast cancer (TNBC) was associated with high rates of cancer recurrence and metastasis and currently no available molecularly target. Accumulating evidences have established the importance of lincRNA-ROR as a marker of cancers. In order to better understand the mechanism of lincRNA-ROR in TNBC, we provided a novel molecular target into the regulatory invasion and metastasis in present research. We found that lincRNA-ROR was upregulated in TNBC cell lines and tissue samples. The aberrant expression of lincRNA-ROR was shown to increase invasion and metastasis in MDA-MB-231 and loss of function by siRNA reverse these process. Furthermore, lincRNA-ROR functions as a competing endogenous RNAs (ceRNA) which sponges miR-145 and therefore upregulate the expression of Mucin1 (MUC1). The expression of MUC1 impacted E-cadherin membrane localization. Together, MUC1 was a potential molecular target may help explain the role of lincRNA-ROR/miR-145 for invasion and metastasis in TNBC cell lines.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Specificity and utility of SubB2M, a new N-glycolylneuraminic acid lectin

Highlights: • SubB2M showed improved specificity and recognition for Neu5Gc containing glycans in a Neu5Ac/Neu5Gc glycan array and by surface plasmon resonance. • Far-western blot analysis showed that SubB2M preferentially binds to serum glycoproteins from bovine over human. • SubB2M detected Neu5Gc-glycoproteins spiked into normal human serum with greater sensitivity than SubB and anti-Neu5Gc IgY. • SubB2M will be a useful tool for the testing of serum and other bodily fluids for cancer diagnosis and prognosis. The B subunit of the subtilase cytotoxin (SubB) recognises N-glycolylneuraminic acid (Neu5Gc) containing glycans, the most prominent form of aberrant glycosylation in human cancers. We have previously engineered SubB by construction of a SubB{sub ΔS106/ΔT107} mutant (SubB2M) for greater specificity and enhanced recognition of Neu5Gc containing glycans. In this study, we further explore the utility of SubB2M as a Neu5Gc lectin by showing its improved specificity and recognition for Neu5Gc containing glycans over the wild-type SubB protein and an anti-Neu5Gc IgY antibody in a N-acetylneuraminic acid (Neu5Ac)/Neu5Gc glycan array and by surface plasmon resonance. Far-western blot analysis showed that SubB2M preferentially binds to bovine serum glycoproteins over human serum glycoproteins. SubB2M was also able to detect Neu5Gc containing bovine glycoproteins spiked into normal human serum with greater sensitivity than the wild-type SubB and the anti-Neu5Gc IgY antibody. These results suggest that SubB2M will be a useful tool for the testing of serum and other bodily fluids for cancer diagnosis and prognosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Developmental endothelial locus-1 prevents development of peritoneal adhesions in mice

Postoperative peritoneal adhesions, fibrous bands formed in the peritoneal cavity following surgery, represent a common, challenging and costly problem faced by surgeons and patients, for which effective therapeutic options are lacking. Since aberrant inflammation is one of the key mechanisms underlying peritoneal adhesion formation, here we set out to study the role of developmental endothelial locus-1 (Del-1), which has been recently identified as an endogenous inhibitor of inflammation, in the formation of postoperative peritoneal adhesions using a mouse model of peritoneal adhesions induced by ischemic buttons. Del-1-deficient mice had a higher incidence of adhesions, and their adhesions had higher quality and tenacity scores. Del-1 deficiency also led to enhanced inflammation mediators and collagen production. Finally, Del-1 supplementation decreased the incidence and severity of postoperative peritoneal adhesions. Taken together, these results indicate a protective role for Del-1 in postoperative peritoneal adhesion formation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA expression profiles in hippocampus from mice with perinatal glyphosate exposure

Glyphosate is the active ingredient in numerous herbicide formulations. The roles of glyphosate in embryo-toxicity and neurotoxicity have been reported in human and animal models. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. However, the role of glyphosate in neuronal development is still not fully understood. Our previous study found that perinatal glyphosate exposure resulted in differential microRNA expression in the prefrontal cortex of mouse offspring. However, the mechanism of glyphosate-induced neurotoxicity in the developing brain is still not fully understood. Considering the pivotal role of Circular RNAs (circRNAs) in the regulation of gene expression, a circRNA microarray method was used in this study to investigate circRNA expression changes in the hippocampus of mice with perinatal glyphosate exposure. The circRNA microarrays revealed that 663 circRNAs were significantly altered in the perinatal glyphosate exposure group compared with the control group. Among them, 330 were significantly upregulated, and the other 333 were downregulated. Furthermore, the relative expression levels of mmu-circRNA-014015, mmu-circRNA-28128 and mmu-circRNA-29837 were verified using quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that stress-associated steroid metabolism pathways, such as aldosterone synthesis and secretion pathways, may be involved in the neurotoxicity of glyphosate. These results showed that circRNAs are aberrantly expressed in the hippocampus of mice with perinatal glyphosate exposure and play potential roles in glyphosate-induced neurotoxicity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Mm9{sub c}irc{sub 0}09056 enhances osteogenesis by targeting BMP7 via CGRP-mediated miR-22–3p

Circular RNAs (circRNAs) are noncoding RNAs that can function as miRNA sponges, post-transcriptionally regulating the expression of genes. Here, we report a novel positive function of mm9{sub c}irc{sub 0}09056 during osteogenesis in regulating bone morphogenetic protein 7 (BMP7) through miR-22–3p. First, we found that calcitonin gene-related peptide (CGRP) had great osteogenesis function on MC3T3 cells. Then aberrant expression of mm9{sub c}irc{sub 0}09056 were confirmed in CGRP-induced cells. Furthermore, the expression of mm9{sub c}irc{sub 0}09056 was up-regulated in the CGRP-induced cells, whereas miR-22–3p was obviously decreased. Silencing of mm9{sub c}irc{sub 0}09056 increased the expression of miR-22–3p and decreased the gene and protein levels of BMP7, RUNX2. Cells proliferation and growth were also inhibited following silengcing. The protein levels of BMP7 and RUNX2 decreased after mimics transfection and increased after inhibitors transfection. In summary, mm9{sub c}irc{sub 0}09056 may function as a sponge for miR-22–3p to regulate osteogenesis in CGRP-induced cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-196b is a prognostic factor of human laryngeal squamous cell carcinoma and promotes tumor progression by targeting SOCS2

Highlights: • Aberrant expression of miR-196b and SOCS2 were found in LSCC samples. • MiR-196b can directly inhibit SOCS2 expression in LSCC cells in vitro. • MiR-196b promotes LSCC cells proliferation and invasion by inhibiting SOCS2. • MiR-196b/SOCS2 pathway are correlated with LSCC progression in clinic. • MiR-196b serves as an effective prognostic factor of LSCC. Laryngeal squamous cell carcinoma (LSCC) has the second highest incidence among the head and neck malignancies. Additionally, the incidence of LSCCs has been recently increasing. Therefore, understanding the mechanisms of LSCC tumorigenesis and identifying novel biomarkers to accurately predict and improve the prognosis of patients with LSCC is extremely important.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

PGC1α is required for the induction of contact inhibition by suppressing ROS

Highlights: • PGC1α is progressively induced with increasing cell density. • The induction of PGC1α represses cellular ROS production through SIRT3, which is required for contact inhibition (CI). • PGC1α knockdown cells exhibit the defects of density-dependent ROS regulation and loss of CI. • PGC1α functions as a determinant of cell-density dependent growth regulation. Contact inhibition (CI) is an important tumor-suppressive mechanism that arrests cell cycle when cells reach high density. Indeed, CI is aberrantly absent in cancer cells and the dysregulation of this can contribute to tumorigenesis. Previously, it has been shown that reactive oxygen species (ROS) levels are repressed at high cell density, which is required for CI, but no molecular mechanism of this ROS regulation has been reported. Here, we show that PGC1α regulates cell density-dependent CI. PGC1α is markedly induced in response to high cell density and suppresses ROS production. Although cellular ROS levels are progressively decreased with increasing cell density, knockdown of PGC1α results in a defect of density-dependent ROS suppression. Importantly, PGC1α knockdown cells become less sensitive to high cell density and exhibit loss of CI. Mechanistically, PGC1α represses ROS production by inducing mitochondrial SIRT3, and thus SIRT3 overexpression rescues the defects of CI by PGC1α knockdown. These results demonstrate that mitochondrial ROS production is a crucial regulator of cell proliferation and identify a new role of PGC1α in CI.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

SURF4 has oncogenic potential in NIH3T3 cells

Highlights: • SURF4 was found to be amplified and highly expressed in the tumor tissues of several human cancer patients. • Patients with tumors exhibiting high SURF4 expression had significantly shorter overall survival than low SURF4 expression. • SURF4 can induce cellular transformation and cell migration in vitro and promotes oncogenic transformation in vivo. SURF4, which is located in the Surfeit gene cluster, encodes for a conserved integral membrane protein containing multiple putative transmembrane regions. However, the physiological role of SURF4 has not been determined. We found that SURF4 demonstrated aberrant amplification and increased expression in the tumor tissues of several human cancer patients. Overexpression of SURF4 led to increased cell proliferation, migration, and maintenance of anchorage-independent growth. In addition, NIH3T3 cells overexpressing SURF4 induced tumor growth in the mice. Collectively, our findings demonstrate that SURF4 has the potential for inducing cellular transformation and cell migration in vitro and has oncogenic transformation ability in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

17β-estradiol protects nucleus pulposus cells from serum deprivation-induced apoptosis and regulates expression of MMP-3 and MMP-13 through promotion of autophagy

Highlights: • 17β-Estradiol can suppress limited serum-induced apoptosis and MMPs in rat NPCs. • 17β-Estradiol activated autopahgic flux in rat NPCs. • 17β-Estradiol can enhancing autophagy in NPCs under serum deprivation. • Promotion of autophagy attenuated serum deprivation-induced pathology in rat NPCs. Serum deprivation is a likely contributor to intervertebral disc (IVD) degeneration (IVDD).17β-estradiol (E2) have been noted to protect nucleus pulposus cells (NPCs) against apoptosis. Autophagy and apoptosis play a paramount role in maintaining the homeostasis of IVD. So far, little research has been published on whether autophagy plays a role for the E2 mediated protection of NPCs. The aim of this study is to understand whether autophagy is involved in the protective effect of E2 against serum deprivation-induced cell apoptosis and expression of matrix metalloproteinase (MMP)-3 and MMP-13. mCherry-GFP-LC3-adenovirus transfection is used to monitor autophagy detection. The expression levels of autophagy-related proteins were measured by Western blotting, Apoptosis and MMPs were detected by flow cytometry and Western blotting. Accordingly, Autophagy and apoptosis was detected in NP cells under serum deprivation conditions, the autophagy incidence began to reached a peak value at 48 h, the apoptosis and MMPs incidence began reached a minimum value treat with E2 (10{sup −7} M). Whereas the combined use of E2 and 3-MA led to a dramatic decrease in autophagy, while aberrantly elevated expression levels of apoptotic and MMPs. These data suggest that serum deprivation-induced apoptosis and MMP-3, MMP-13, which was efficiently suppressed by the E2 through promoting autophagy in rat NPCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

PTP1B promotes the malignancy of ovarian cancer cells in a JNK-dependent mechanism

Highlights: • High expression level of PTP1B is linked to the malignancy phenotypes of ovarian cancer cells. • The expression level of PTP1B can affect tumor growth. • PTP1B regulates key factors involved in cell invasion and migration. • PTP1B promoted the malignancy of cancer cells in a JNK-dependent mechanism. Ovarian cancer is the leading cause of death from gynecological malignancies in women. Diagnosis at the early stage remains challenging and efficient treatment is still highly needed. The development and progression of this cancer is associated with many genetic and epigenetic changes, representing the dysregulation of a highly complex signaling network. Previous studies found that protein-tyrosine phosphatase 1 B (PTP1B) was aberrantly expressed in many types of ovarian cancer cells. The exact role of this protein, however, remains controversial. We found that PTP1B was highly expressed in several ovarian carcinoma cell lines. Changing its expression level strongly affected the malignancy phenotypes of the cultured cancer cells and growth of tumors in nude mice. Further analysis at the molecular level found that overexpression of PTP1B activated the JNK (c-Jun N-terminal kinase) signaling pathway and impacted a set of factors involved in cancer metastasis. Overall, our study suggested that overexpression of PTP1B could be a driving factor in the tumorigenesis and progression of ovarian cancer and restoring the normal expression level of this signaling molecule may represent a promising strategy in treating this disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Unfolding of IgG domains detected by non-reducing SDS-PAGE

Highlights: • Aberrant artefactual mAb masses and size heterogeneity noted by non-reducing SDS-PAGE. • This effect depends on pre-electrophoresis sample heating temperatures and conditions. • These phenomena are also observed for a commercial human IgG{sub 1} polyclonal antibody. • Multiple observed bands hypothesized to reflect IgG domain thermal unfolding in SDS. • These results are likely relevant to analyses of many monoclonal and polyclonal Abs. Monoclonal antibodies are very important in modern therapeutics and constitute a substantial percentage of newly approved drugs. Every therapeutic monoclonal antibody must be analyzed for structural and functional integrity, and all protein heterogeneities need to be identified and quantified. The conformational stabilities of the monoclonal antibodies are also important for antibody storage and handling stabilities. One of the first and simplest of the structural analysis techniques utilized is SDS-PAGE, which can be performed both with and without prior reduction to break disulfide bonds. This permits sizing of both heavy and light chains in the reduced condition, and sizing of the intact antibody and any disulfide aggregates in the non-reduced condition. Analyzing our human anti-cocaine monoclonal antibody, we noted unexpectedly larger apparent molecular weights and apparent protein size heterogeneities using non-reducing SDS-PAGE. These apparent molecular weight heterogeneities are not consistent with other analysis techniques. Heterogeneities were noted using several heating and pre-electrophoretic sample preparation protocols, and are modified by the inclusion of small concentrations of certain alcohols such as propanol and butanol. All of these unexpected results were also observed for a commercial human IgG{sub 1} antibody, suggesting that these observations are applicable to IgGs in general. Thus, careful attention must be paid to the interpretation of non-reducing SDS-PAGE results for IgGs. It is hypothesized that differential thermal unfolding of the Fab, CH2 and CH3 domains of the IgGs in SDS give rise to the stable, discrete bands observed using different heating protocols prior to non-reducing SDS-PAGE.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MicroRNA-124-3p represses cell growth and cell motility by targeting EphA2 in glioma

Highlights: • miR-124-3p inhibits glioma cell proliferation. • miR-124-3p inhibits glioma cell motility. • miR-124-3p suppresses glioma cell EMT. • EphA2 is a candidate target of miR-124-3p. MiR-124-3p and EphA2 are aberrantly expressed in glioma tissue specimens. In the present study, we firstly investigated that miR-124-3p inhibits EphA2 expression mediated by binding its 3′-UTR to regulate the progression of human glioma. The U87MG and LN229 cells were transfected with miR-124-3p mimics and/or siRNA-EphA2, and then the role of miR-124-3p and EphA2 in the colony-formation, cell-cycle, migration and invasion of glioma cells in vitro were examined. Proteins involved in the epithelial-mesenchymal transition were examined using western blot. The results showed that miR-124-3p was significantly downregulated in glioma tissues, whereas a marked upregulation of EphA2 expression was found. Colony-formation and flow cytometry assays demonstrated that EphA2 downregulation or miR-124-3p mimics caused growth and cell-cycle inhibition in glioma. Transwell migration and invasion assays demonstrated that EphA2 downregulation or miR-124-3p mimics suppressed the migration and invasion of glioma cells. EphA2 downregulation or miR-124-3p mimics reduced the level of vimentin in U87MG and LN229 cells. In conclusion, miR-124-3p was found to suppress the growth, migration and invasion of glioma cells in vitro via EphA2. Furthermore, we validated miR-124-3p enforced its biological modulation via targeting EphA2 through the rescue experiment. Conclusively, our study proclaimed that miR-124-3p can counteract the malignant phenotypes of glioma cells by the inhibitory effect of the EphA2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

ABT-199-mediated inhibition of Bcl-2 as a potential therapeutic strategy for nasopharyngeal carcinoma

Highlights: • ABT-199 can effectively induce nasopharyngeal carcinoma cell apoptosis free of cytotoxic agent. • ABT-199 can cause elevated Noxa expression in nasopharyngeal carcinoma. • Dual Mcl-1/Bcl-2 inhibition with ABT-199 and Mcl-1 inhibitor S63845 works synergistically and demonstrates promise for future NPC treatment. Aberrant overexpression of Bcl-2 protein has been detected in 80% of nasopharyngeal carcinoma (NPC), and Bcl-2 family proteins are implicated in both NPC oncogenesis and chemotherapy resistance. Previous studies have shown that while treatment of NPC cells with Bcl-2 family inhibitors alone is rarely effective, concomitant treatment with a cytotoxic reagent such as cisplatin can increase efficacy through a synergistic effect. The aim of the current work was to determine how we might increase the efficacy of Bcl-2 family inhibitors in the absence of cytotoxic reagents, which are associated with negative side effect profiles.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Saturated fatty acids-induced miR-424–5p aggravates insulin resistance via targeting insulin receptor in hepatocytes

Highlights: • miR-424–5p expression is upregulated by SFA or HFD-induced obesity in hepatocytes. • Mechanistically, miR-424–5p targets 3′UTR of INSR directly, thereby downregulating INSR at the post-transcriptional step. • The ectopic expression of miR-424–5p impairs insulin signaling and insulin-induced glycogen synthesis in hepatocytes. • This study highlights the potential role of miR-424–5p in the insulin signaling pathway through the repression of INSR. The excessive intake of saturated fatty acids (SFA) causes obesity and liver steatosis, which are major risk factors for insulin resistance and type 2 diabetes. Although the expression of certain microRNAs (miRNAs) targeting the insulin signaling molecules are regulated aberrantly in SFA-induced obesity, their implications on hepatic insulin resistance are largely unknown. This study examined the associations of miR-424–5p, which is induced by SFA, with the development of insulin resistance. SFA palmitate (PA)-treated HepG2 cells and high fat diet (HFD)-induced obese mouse livers showed an impairment of insulin signaling due to a significant decrease in INSR and IRS-1 expression. Based on expression profiling and qRT-PCR analysis, miR-424–5p, which presumably targets the 3′UTR of INSR, was upregulated in both PA-treated HepG2 cells and the liver of HFD-fed mice. miR-424–5p was found to target the 3′UTR of INSR directly and downregulated INSR expression at the post-transcriptional step. Furthermore, the overexpression of miR-424–5p suppressed INSR expression significantly, leading to impaired insulin signaling and glycogen synthesis in hepatocytes. A novel mechanism for how SFA-induced miR-424–5p impairs insulin signaling through the targeting of INSR is reported. In addition, the crucial role and underlying mechanism of miR-424–5p in the obesity-induced hepatic insulin resistance is explained.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Upregulated circular RNA circ{sub 0}016760 indicates unfavorable prognosis in NSCLC and promotes cell progression through miR-1287/GAGE1 axis

Non-small cell lung cancer (NSCLC) is an aggressive malignancy with increasing worldwide incidence and is characterized by dismal prognosis due to its early recurrence and metastasis. Accumulating evidence documented that aberrantly expressed circular RNAs (circRNAs) are critically involved in tumorigenesis. In the current study, we focused on a novel circRNA, circ{sub 0}016760 in NSCLC. qRT-PCR was carried out to determine the expression level of circ{sub 0}016760 in tissue samples and cell lines. The clinical value of circ{sub 0}016760 was also investigated. The functions of circ{sub 0}016760 was explored by CCK-8, colony formation, flow cytometry, Transwell and animal experiments. Luciferase reporter assays were conducted to investigate the association between circ{sub 0}016760 and miR-1287 and miR-1287 and GAGE1. We found that circ{sub 0}016760 was enhanced in NSCLC tissues and cells and the upregulation of circ{sub 0}016760 is associated with advanced TNM stages, lymph node metastasis and adverse prognosis in NSCLC patients. Moreover, circ{sub 0}016760 could significantly promote cell growth and metastatic properties and inhibit cell apoptosis in NSCLC cells. In mechanism, circ{sub 0}016760 functioned as a sponge for miR-1287 and regulated the expression of GAGE1. Subsequently, functional assays illustrated that the oncogenic properties of circ{sub 0}016760 is partly attribute to the regulation of miR-1287/GAGE1 axis. In summary, circ{sub 0}016760/miR-1287/GAGE1 signaling might play vital roles in the tumorigenesis and progression of NSCLC.

60 APPLIED LIFE SCIENCES↗