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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 379 records · Page 21
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

LncRNA SNHG20 knockdown suppresses the osteosarcoma tumorigenesis through the mitochondrial apoptosis pathway by miR-139/RUNX2 axis

Highlights: • SNHG20 was up-regulated in osteosarcoma samples and its high-expression indicated the poor prognosis. • SNHG20 knockdown inhibited the proliferation, invasion and promoted the apoptosis of osteosarcoma cells in vitro. • SNHG20 knockdown up-regulated the expression levels of caspase-9, caspase-3 and Bax. • miR-139 both targeted with the 3′-UTR of RUNX2 and SNHG20. • SNHG20/miR-139/RUNX2 axis modulates the osteosarcoma tumorigenesis and apoptosis via mitochondrial apoptosis. Increasing evidence has indicated the important roles of long noncoding RNAs (lncRNAs) in human osteosarcoma tumorigenesis. In present study, we aim to investigate the roles of lncRNA SNHG20 (small nucleolar RNA host gene 20) in osteosarcoma tumorigenesis and explore the in-depth molecular mechanism. Results showed that lncRNA SNHG20 expression was up-regulated in osteosarcoma samples and its high-expression indicated the poor prognosis. Loss-of-functional experiments indicated that SNHG20 knockdown inhibited the proliferation, invasion and induced the apoptosis of osteosarcoma cells in vitro. Specifically, SNHG20 knockdown up-regulated the expression levels of caspase-9, caspase-3 and Bax, indicating that SNHG20 knockdown accelerated the apoptosis of osteosarcoma cells via mitochondrial apoptosis pathway. Bioinformatics analysis revealed that miR-139 both targeted with the 3′-UTR of runt-related transcription factor 2 (RUNX2) and SNHG20, which was verified by luciferase reporter assay and RNA immunoprecipitation (RIP). In conclusion, our data reveals that lncRNA SNHG20/miR-139/RUNX2 axis modulates the osteosarcoma tumorigenesis and apoptosis via mitochondrial apoptosis pathway, providing a novel insight for the pathophysiological process.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

4-Hydroxy-tetrahydrodipicolinate reductase from Neisseria gonorrhoeae – structure and interactions with coenzymes and substrate analog

Highlights: • N. gonorrhoeae is an obligate human pathogen which is a leading cause of communicable diseases. • 4-Hydroxy-tetrahydrodipicolinate reductase from N. gonorrhoeae (NgDapB) is a new drug target, and its structure was determined. • ITC we have demonstrated and characterized binding of NADH, NADPH and an inhibitor (2,6-PDC) to NgDapB. • In the case of NgDapB, the ITC results suggest random sequential mechanism for substrate binding. • A large scale analysis of DapBs' sequences revealed that DapBs can be segregated into three distinct groups. Neisseria gonorrhoeae, an obligate human pathogen, is a leading cause of communicable diseases globally. Due to rapid development of drug resistance, the rate of successfully curing gonococcal infections is rapidly decreasing. Hence, research is being directed toward finding alternative drugs or drug targets to help eradicate these infections. 4-Hydroxy-tetrahydrodipicolinate reductase (DapB), an important enzyme in the meso-diaminopimelate pathway, is a promising target for the development of new antibiotics. This manuscript describes the first structure of DapB from N. gonorrhoeae determined at 1.85 Å. This enzyme uses NAD(P)H as cofactor. Details of the interactions of the enzyme with its cofactors and a substrate analog/inhibitor are discussed. A large scale bioinformatics analysis of DapBs' sequences is also described.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Down-regulation of miR-193a-3p promotes osteoblast differentiation through up-regulation of LGR4/ATF4 signaling

Highlights: • miR-193a-3p was decreased during osteoblast differentiation. • Inhibition of miR-193a-3p promoted osteoblast differentiation. • LRG4 was a target gene of miR-193a-3p. • miR-193a-3p regulates osteoblast differentiation by LGR4/ATF4. Emerging evidence indicates that microRNAs (miRNAs) are crucial regulators of osteoblast differentiation. A previous study has reported that miR-193a-3p expression is altered during the induction of osteoblast differentiation. However, the precise biological function and regulatory mechanism of miR-193a-3p during osteoblast differentiation remains unclear. In this study, we aimed to investigate the precise role and underlying mechanism of miR-193a-3p in regulating osteoblast differentiation. The results showed that miR-193a-3p expression was significantly down-regulated during the induction of osteoblast differentiation. Functional experiments demonstrated that the overexpression of miR-193a-3p impeded osteoblast differentiation while miR-193a-3p inhibition promoted osteoblast differentiation. Bioinformatics analysis and a luciferase assay revealed that leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), a critical regulator of osteoblast differentiation, was a target gene of miR-193a-3p. We showed that miR-193a-3p negatively regulated the expression of LGR4 and activating transcription factor 4 (ATF4). Moreover, the knockdown of LGR4 or ATF4 significantly reversed the promotion effect of miR-193a-3p inhibition on osteoblast differentiation. Overall, these findings demonstrate that miR-193a-3p regulates osteoblast differentiation by modulating LGR4/ATF4 signaling and suggests that the miR-193a-3p/LGR4/ATF4 regulation axis may play an important role in regulating bone remodeling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Overexpression of circular RNA circ{sub 0}01569 indicates poor prognosis in hepatocellular carcinoma and promotes cell growth and metastasis by sponging miR-411-5p and miR-432-5p

Emerging evidence indicated that abnormally expressed circular RNAs (circRNAs) are critically involved in tumorigenesis and development of several cancers. However, the study relevant to the relationship between circRNAs and hepatocellular carcinoma (HCC) is rare. In this study, the expression of circ{sub 0}01569 in HCC tissue specimens and cells were determined by qRT-PCR. The clinical relevance of circ{sub 0}01569 was also analyzed. In addition, loss-of-function and gain-of-function assays were conducted to explore the biological functions of circ{sub 0}01569. Furthermore, tumor formation and lung metastasis studies were induced to confirm the in vitro data. Mechanistically, bioinformatics analysis and luciferase reporter assays were conducted to illustrate the underlying mechanism of circ{sub 0}01569. The results indicated that circ{sub 0}01569 was overexpressed in HCC tissue samples and cells. This overexpression is correlated with larger tumor size, advanced TNM stages and unfavorable prognosis in the patients with HCC. Additionally, circ{sub 0}01569 significantly facilitated HCC cell growth, migration and invasion. The animal studies further confirmed the in vitro results. More importantly, circ{sub 0}01569 could directly sponge miR-411-5p and miR-432-5p. The oncogenic functions of circ{sub 0}01569 is partially dependent on its regulation on miR-411-5p and miR-432-5p. In summary, circ{sub 0}01569/miR-411-5p/miR-432-5p regulatory signaling might be a rational HCC-related therapeutic target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A novel long noncoding RNA OECC promotes colorectal cancer development and is negatively regulated by miR-143-3p

Emerging evidence indicates that aberrant long non-coding RNA (lncRNA) expression contributes to CRC pathogenesis. To explore the biological functions of lncRNAs in CRC and to identify the underlying mechanisms, we first conducted a lncRNA microarray assay to investigate lncRNA expression patterns in CRC. We identified a novel lncRNA OECC, originating from chromosome 8q24 that is highly expressed in CRC tissues and cell lines and has a positive correlation with liver metastasis. Attenuation of lncRNA OECC expression prohibited CRC cell proliferation, induced apoptosis, and inhibited migration. Furthermore, an inverse correlation between lncRNA OECC and miR-143-3p was observed. Bioinformatic analyses predicted, and a luciferase reporter assay demonstrated, that lncRNA OECC is a direct target of miR-143-3p, leading to down-regulation in the expression of its target genes, the NF-κB and p38 MAPK pathways. Taken together, our results suggest that lncRNA OECC is overexpressed in CRC and may play an oncogenic role through NF-κB and p38 MAPK pathway activation via miR-143-3p.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long noncoding RNA LINC00339 aggravates doxorubicin-induced cardiomyocyte apoptosis by targeting MiR-484

Highlights: • LncRNA LINC00339 was highly expressed in DOX stimulated primary rat cardiomyocytes and H9c2 cells. • Knockdown of LINC00339 significantly reduced primary rat cardiomyocytes and H9c2 cells proliferation and apoptosis. • LINC00339 acts as a critical pro-apoptosis lncRNA that aggravates DOX-induced cardiac remodeling by miR-484. Abnormally expressed long noncoding RNAs (lncRNAs) has been recognized as one of the key source in cardiac diseases. However, the role of lncRNA in doxorubicin (DOX)-induced cardiotoxicity remains largely unknown. In previous studies, we have screened some aberrantly expressed lncRNAs from an animal model for DOX-induced cardiotoxicity, and LINC00339 is one of the highly expressed lncRNA. In this study, we validated and further explored its regulatory mechanisms using in vitro model systems. Primary cultured myocardial cell (PC) and H9C2 cell line were treated with different concentrations of DOX and the expression of LINC00339 were markedly up-regulated. However, knockdown of endogenous LINC00339 by its siRNA improved cells proliferation activity and reduced cardiomyocyte apoptosis. Further experiments showed the opposite trend of expression between LINC00339 and miR-484. Bioinformatics analysis and luciferase reporter assay indicated that LINC00339 directly binds to miR-484. Moreover, miR-484 inhibitor abrogated the collagen synthesis inhibition induced by LINC00339. These findings reveal a novel function of the LINC00339/miR-484 axis in DOX-induced cardiotoxicity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Hypermethylated KCNQ1 acts as a tumor suppressor in hepatocellular carcinoma

Highlights: • Decreased KCNQ1 expression was associated with a poor prognosis in HCC. • KCNQ1acts as a tumor suppressor in HCC. • KCNQ1 interacts with β-catenin to affect its subcellular distribution. • Activation of β-Catenin restores the inhibitory roles of KCNQ1 in HCC. Potassium (K{sup +}) channels are dysregulated in tumor tissues and functionally these channels contribute significantly to the malignant phenotypes of the cancer cells, including cell apoptosis, chemo- and radio-resistance, proliferation, and migration. However, little is known about the potential implications of K{sup +} channels in hepatocellular carcinoma (HCC). The aim of the current study was to investigate the expression profile of KCNQ1 in HCC and assess its possible cellular implications as well as mechanism to disease progression. Using real-time qPCR and western blotting technique, we found that KCNQ1 was frequently down-regulated in HCC cell lines and tissues, and HCC patients with lower KCNQ1 expression had a poor prognosis. Specifically, DNA hypermethylation of KCNQ1 promoter resulted in its downregulation in HCC. Bioinformatic analysis indicated a regulatory role of KCNQ1 in the epithelial-to-mesenchymal transition process. Gain-of-function study showed that KCNQ1 exhibited remarkable inhibitory roles on tumor metastasis in vitro and in vivo. Mechanistically, KCNQ1 can interact with β-catenin to affect its subcellular distribution and subsequently reduce the activity of Wnt/β-catenin signaling, which further blocks the expression of its downstream targets, including c-Myc, MMP7, and CCND1. Restoration of β-catenin activity largely compromised the tumor-suppressive roles of KCNQ1 in the invasive capacity of HCC cells. In conclusion, KCNQ1 is down-regulated in HCC and may suppress HCC metastasis, which could represent a prognostic marker and promising therapeutic target for HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/β-catenin pathway

While recent evidence has uncovered that circular RNAs (circRNAs) are vital regulators of carcinogenesis, their role in papillary thyroid cancer (PTC) is not clearly understood. In this study, we reveal that lower levels of circRNA circ-ITCH are expressed in PTC tissues than in normal adjacent tissues. Gain-of-functional assays show that circ-ITCH overexpression suppresses PTC cell proliferation and invasion and promotes apoptosis in vitro. Overexpression of circ-ITCH also leads to impaired tumor growth in vivo. Bioinformatics analysis and luciferase reporter assays demonstrate that circ-ITCH sponges miR-22-3p to upregulate the expression of CBL, an E3 ligase of nuclear β-catenin. Elevated levels of CBL suppress activation of the Wnt/β-catenin pathway and consequently attenuates PTC progression. In summary, our study reveals a novel signaling pathway of circ-ITCH/miR-22-3p/CBL/β-catenin involved in PTC development and progression.

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

MiR-429 suppresses neurotrophin-3 to alleviate perineural invasion of pancreatic cancer

Highlights: • MiR-429 is downregulated in pancreatic cancer tissues and cells. • MiR-429 functions to inhibit cancer cell proliferation and invasion. • MiR-429 directly targets to NT-3 mRNA. • MiR-429 suppress NT-3 in cancer cells to resist the attraction TrkC in PC12 cells. • NT-3-TrkC signaling promotes PC12 neurite outgrowth and neuropathic pain. Perineural invasion (PNI) potentially increases the risk of relapse and abdominal pain in patients with pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanisms of PNI of PDAC is incompletely revealed. Our study aimed to investigate roles of miR-429 in modulating PNI in PDAC. We found that miR-429 was downregulated in PDAC cancer tissues and was profoundly decreased in tissues with PNI. It was reduced in nine of the ten examined pancreatic cancer cell lines. MiR-429 mimics restored its cellular expressions in MIA PaCa-2 and BxCP3 cells and significantly suppressed cell viability and invasion of the cancer cells. The online bioinformatic software predicted that neurotrophin-3 (NT-3) was a potential target gene of miR-429. It was showed that NT-3 mRNA elevated in PC cancer tissues, especially in patients presenting PNI. MiR-429 upregulation substantially suppressed the NT-3 mRNA and secretion in cancer cells. Also, the dual luciferase reporter assays confirmed the interaction between miR-429 and NT-3. When co-culturing the two PDAC cells with PC-12 cells, the invaded cell counts significantly increased comparing with the sole culture of cancer cells. However, miR-429 mimic transfection or NT-3 blocking retarded the cancer invasion in the co-culture system. Besides, we found that cancer cells conditioned medium (CM) treatment significantly increased the neurite outgrowth percentage in PC-12 cells, which was suppressed by culturing with CM from miR-429 mimics-transfected cells. In the CM cultured PC-12 cells, NT-3 receptor TrkC as well as pain-related proteins TRPV1 and TRPV2 significantly elevated. Collectively, miR-429 potentially suppressed neurotrophin-3 to alleviate PNI of PDAC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The proteomic study of serially passaged human skin fibroblast cells uncovers down-regulation of the chromosome condensin complex proteins involved in replicative senescence

Dermal fibroblast is one of the major constitutive cells of skin and plays a central role in skin senescence. The replicative senescence of fibroblasts may cause skin aging, bad wound healing, skin diseases and even cancer. In this study, a label-free quantitative proteomic approach was employed to analyzing the serial passaged human skin fibroblast (CCD-1079Sk) cells, resulting in 3371 proteins identified. Of which, 280 proteins were significantly changed in early passage (6 passages, P6), middle passage (12 passages, P12) and late passage (21 passages, P21), with a time-dependent decrease or increase tendency. Bioinformatic analysis demonstrated that the chromosome condensin complex, including structural maintenance of chromosomes protein 2 (SMC2) and structural maintenance of chromosomes protein 4 (SMC4), were down-regulated in the serially passaged fibroblast cells. The qRT-PCR and Western Blot experiments confirmed that the expression of these two proteins were significantly down-regulated in a time-dependent manner in the subculture of human skin fibroblasts (HSFb cells). In summary, we used serially passaged human skin fibroblast cells coupled with quantitative proteomic approach to profile the protein expression pattern in the temporal progress of replicative senescence in HSFb cells and revealed that the down-regulation of the chromosome condensin complex subunits, such as SMC2 and SMC4, may play an important role in the fibroblast senescence.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA cancer susceptibility candidate 15 accelerates the breast cancer cells progression via miR-153–3p/KLF5 positive feedback loop

Highlights: • CASC15 expression level was aberrantly high-expressed in breast cancer tissue specimens and cells. • Loss-of-functional experiments showed that knockdown of CASC15 suppressed the malignant behaviors of breast cancer cells. • CASC15 functioned as ceRNA of miR-153–3p, besides, miR-153–3p targeted the 3‘-UTR of KLF5 mRNA. • KLF5 binds with the promoter region of CASC15 and activates the transcription. Emerging literature have illustrated the vital regulatory roles of long noncoding RNAs (lncRNAs) on the breast cancer tumorigenesis. Although series of researches have been proceeded on the pathogenesis, there are still much of unsolved mysteries worth investigating. This study uncovered that CASC15 expression level was aberrantly high-expressed in breast cancer tissue specimens and cells. Functionally, the loss-of-functional experiments showed that knockdown of CASC15 suppressed the malignant behaviors of breast cancer cells, such as proliferation, invasion and tumor growth in vitro and vivo. Mechanically, we confirmed that CASC15 functioned as a competing endogenous RNA (ceRNA) of miR-153–3p, besides, miR-153–3p targeted the 3‘-UTR of KLF5 mRNA utilizing the bioinformatics online tools, luciferase reporter assay and RNA immunoprecipitation. Interestingly, we confirmed that the transcription factor KLF5 binds with the promoter region of CASC15 and activates the transcription. In conclusion, we validated the positive feedback loop of KLF5/CASC15/miR-153–3p/KLF5 in the acceleration of breast cancer malignant behaviors and tumorigenesis, suggesting the important biologic roles of CASC15 on the breast cancer tumorigenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

SOX10-dependent CMTM7 expression inhibits cell proliferation and tumor growth in gastric carcinoma

Highlights: • The expression pattern of CMTM7 and SOX10 are down-regulated in GC. • SOX10 is a transcriptional regulator of CMTM7 in GC. • SOX10 mediate the proliferation and tumor formation of gastric cancer by regulating the expression of CMTM7. Numerous studies have shown that CMTM family members have a variety of important roles in the occurrence and progression of cancer. CMTM7 has also been reported to be down-regulated in some digestive system tumors, but the expression patterns and pathological role of CMTM7 in gastric cancer remains unclear. In this study, we found that both CMTM7 and SOX10 were significantly down-regulated in gastric cancer tissues compared with paracancerous tissues, and the expression pattern of CMTM7 and SOX10 were strongly correlated (r = 0.6455, p < 0.001). Further, through bioinformatics technology and luciferase assay, we identify that SOX10 can be a transcriptional regulator of CMTM7 to mediate the expression of CMTM7 in gastric cancer. In addition, we found silencing the expression of CMTM7 can increase the proliferation and tumorigenesis of gastric cancer cells in vivo and in vitro. More interestingly, overexpression of SOX10 in cell lines stably silencing CMTM7 expression significantly inhibited the proliferation and tumor growth of gastric cancer. Therefore, our results demonstrate that CMTM7 as a tumor suppressor is down-regulated in gastric cancer, and SOX10 can regulate the proliferation and tumor formation of gastric cancer by regulating the expression of CMTM7.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MicroRNA-98-5p ameliorates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by inhibiting Bach1 and promoting Nrf2/ARE signaling

Highlights: • miR-98 expression was altered in neurons with OGD/R treatment. • miR-98-5p inhibited OGD/R-induced apoptosis and ROS production. • miR-98-5p targets and regulates Bach1. • miR-98-5p regulates OGD/R-induced injury by targeting Bach1. • miR-98-5p regulates Nrf2/ARE signaling by targeting Bach1. MicroRNA-98-5p (miR-98-5p) is a stress-related microRNA (miRNA) that plays an important role in regulating cell survival, apoptosis, and oxidative stress in multiple cell types and diseases. However, little is known about the role of miR-98-5p in cerebral ischemia/reperfusion injury. In this study, we investigated the role and mechanism of miR-98-5p in regulating neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R), an in vitro model of cerebral ischemia/reperfusion injury. We found that miR-98 expression was significantly altered in neurons in response to OGD/R treatment. Functional experiments showed that overexpression of miR-98-5p inhibited OGD/R-induced apoptosis and reactive oxygen species (ROS) production in neurons, whereas inhibition of miR-98-5p showed the opposite effect. Interestingly, bioinformatics analysis predicted that BTB and CNC homology 1 (Bach1) was a potential target gene of miR-98-5p, that was verified by dual-luciferase reporter assay. Moreover, overexpression of miR-98-5p inhibited Bach1 expression while suppression of miR-98-5p promoted Bach1 expression in neurons. Notably, miR-98-5p was shown to regulate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the activity of the antioxidant response element (ARE). However, overexpression of Bach1 or silencing of Nrf2 significantly abolished the miR-98-5p-mediated neuroprotective effect. Overall, these results demonstrate that miR-98-5p ameliorates OGD/R-induced neuronal injury in vitro through targeting to promote activation of Nrf2/ARE signaling. Our study suggests that miR-98-5p may play a potential role in cerebral ischemia/reperfusion injury and represents a potential therapeutic target for neuroprotection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in acute myeloid leukemia cells via sponging miR-203

Highlights: • Circular RNA-100290 expression is increased in AML patients. • Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in AML cells. • Circular RNA-100290 interacts with miR-203/Rab10 axis. Circular RNA (CirRNA) is a type of noncoding RNA that has been shown to play a unique role in tumor development and other fields in recent years. In this study, we aimed to explore the biological role of hsa{sub c}irc{sub 1}00290 in acute myeloid leukemia (AML). First, we found that the expression of hsa{sub c}irc{sub 1}00290 was increased in human AML samples and cell lines. Down-regulation of hsa{sub c}irc{sub 1}00290 significantly suppressed cell proliferation of AML cells. Silencing hsa{sub c}irc{sub 1}00290 also dramatically induced cell cycle arrest and apoptosis. Bioinformatic prediction and luciferase assay revealed that hsa{sub c}irc{sub 1}00290 and Rab10 were targeted by miR-203. Validation experiments verified that hsa{sub c}irc{sub 1}00290 was co-expressed with Rab10 and was negatively correlated with miR-203 expression. Moreover, rescue experiments demonstrated that miR-203 inhibitor could reverse the role of hsa{sub c}irc{sub 1}00290 knockdown on proliferation and apoptosis in AML cells. Overall, the present study identifies the crucial regulation of hsa{sub c}irc{sub 1}00290 in AML cell proliferation and apoptosis via targeting the miR-203/Rab10 axis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA LINC00319 accelerates ovarian cancer progression through miR-423-5p/NACC1 pathway

Highlights: • LINC00319 is upregulated in ovarian cancer. • LINC00319 promotes ovarian cancer proliferation, migration and invasion. • LINC00319 promotes NACC1 expression by interacting with miR-423-5p. • LINC00319 promotes ovarian cancer progression relying on miR-423-5p/NACC1 pathway. Long noncoding RNA (lncRNA) LINC00319 has been reported to promote carcinogenesis of lung cancer and cutaneous squamous cell carcinoma. However, the role and mechanism of LINC00319 in ovarian cancer progression is unclear. In this study, LINC00319 expression was found to be upregulated in ovarian cancer tissues and cell lines. And our evidence showed that LINC00319 could be a potential prognostic biomarker for patients with ovarian cancer. Cell Counting Kit-8 (CCK-8), colony formation and transwell assays indicated that LINC00319 upregulation promoted proliferation, migration and invasion of ovarian cancer cells. Bioinformatics analysis and luciferase reporter assay revealed that LINC00319 worked as the sponge for miR-423-5p. Furthermore, miR-423-5p directly targeted NACC1. qRT-PCR and western blot results demonstrated that LINC00319 upregulates NACC1 expression through inhibiting miR-423-5p in ovarian cancer cells. Moreover, we observed an inverse expression correlation between miR-423-5p and LINC00319 or between miR-423-5p and NACC1 in ovarian cancer tissues. Finally, rescue assay showed that NACC1 restoration rescued the potentials of proliferation, migration and invasion in LINC00319-depleted ovarian cancer cells. In conclusion, our findings demonstrated that LINC00319 promotes ovarian cancer progression through upregulating NACC1 expression by restraining miR-423-5p.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long noncoding RNA MAGI2-AS3 regulates CCDC19 expression by sponging miR-15b-5p and suppresses bladder cancer progression

Highlights: • Expression of MAGI2-AS3, miR-15b-5p and CCDC19 in BCa. • MAGI2-AS3 regulates miR-15b-5p/CCDC19 cascade expression in BCa. • CCDC19 knockdown partly reverses the effects caused by MAGI2-AS3 overexpression in vitro. • MAGI2-AS3 suppresses BCa growth in vivo. Bladder cancer (BCa) belongs to a popular urological malignancy and leads to large numbers of deaths worldwide. Recently, emerging evidences indicate that long noncoding RNAs (lncRNAs) are closely related with BC occurrence and progression. However, the function of lncRNA MAGI2-AS3 remains poorly understood in BC. In this present study, we screened out a novel lncRNA MAGI2-AS3 whose expression was downregulated in BCa tissues. We showed that MAGI2-AS3 downregulation in BCa patients indicated a poor prognosis. Functionally, we showed that MAGI2-AS3 overexpression inhibits proliferation, migration and invasion of BCa cells. Moreover, ectopic expression of MAGI2-AS3 suppresses BCa growth in vivo. Bioinformatics analysis revealed that MAGI2-AS3 could serve as a competing endogenous RNA (ceRNA) for miR-15b-5p. In the meantime, miR-15b-5p directly targeted CCDC19, a tumor suppressor in BCa. Rescue assays demonstrated that knockdown of CCDC19 restored the proliferation, migration and invasion of BCa cells suppressed by MAGI2-AS3 overexpression. In conclusion, this study identified a novel mechanism that MAGI2-AS3/miR-15b-5p/CCDC19 signaling pathway regulates BCa progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Linc01230, transcriptionally regulated by PPARγ, is identified as a novel modifier in endothelial function

Highlights: • Linc01230 expression was reduced by ox-LDL treatment in endothelial cells. • Linc01230 was transcriptionally promoted by PPARγ. • PPARγ directly bound to linc01230 promoter, predicted by bioinformatics and confirmed by ChIP. • Gain-and-loss of functions revealed that linc01230 alleviates ox-LDL-induced endothelial dysfunction. Evidence is growing that PPARγ could improve the bioavailability of NO in pathological conditions to maintain endothelial function by activating Akt/eNOS pathway. LincRNAs participate in regulating development of cardiovascular diseases. Although investigations have been made to delineate the function of PPARγ and lincRNAs, little is known about the regulation relationship between them, especially in endothelial cells. In this study, we not only verified that PPARγ could antagonize the adverse effects brought from ox-LDL, but also found a novel factor related to PPARγ, named linc01230. According to our study, PPARγ transcriptionally regulated linc01230 by specifically combining with two binding regions, which have superposition effect, in the upstream of linc01230 promoter. In addition, linc01230 reduced ox-LDL induced endothelial dysfunction and affected the phosphorylation of Akt. These results conclude linc01230 as a novel modifier in PPARγ–mediated activation of Akt in endothelial function.

60 APPLIED LIFE SCIENCES↗