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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 829 records · Page 46
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Long non-coding RNA UCA1/miR-182/PFKFB2 axis modulates glioblastoma-associated stromal cells-mediated glycolysis and invasion of glioma cells

Glioblastoma (GB) is the most common and deadliest malignant primary brain tumor with a high recurrence. In this study, lncRNA UCA1/miR-182 axis has been regarded as a nodal driver of glioma invasion mediated by GB-associated stromal cells (GASCs) and GASC-secreted chemokine CXCL14. In clinical specimens, CXCL14 upregulation in GASCs also correlated with poor prognosis. Notably, CXCL14-high GASCs mediated lncRNA UCA1 upregulation and miR-182 downregulation in glioma cells. Moreover, miR-182 directly bound to the fructose-2,6-biphosphatase PFKFB2; UCA1/miR-182 axis thereby modulated GASC-induced glycolysis in glioma cells. Overall, UCA1/miR-182/PFKFB2 axis modulates chemokine CXCL14 secretion, glycolysis and invasion of glioma cells in GASCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

RNA-Seq analysis of global transcriptomic changes suggests a roles for the MAPK pathway and carbon metabolism in cell wall maintenance in a Saccharomyces cerevisiae FKS1 mutant

FKS1 encodes a β-1,3-glucan synthase, which is a key player in cell wall assembly in Saccharomyces cerevisiae. Here we analyzed the global transcriptomic changes in the FKS1 mutant to establish a correlation between the changes in the cell wall of the FKS1 mutant and the molecular mechanism of cell wall maintenance. These transcriptomic profiles showed that there are 1151 differentially expressed genes (DEGs) in the FKS1 mutant. Through KEGG pathway analysis of the DEGs, the MAPK pathway and seven pathways involved in carbon metabolism were significantly enriched. We found that the MAPK pathway is activated for FKS1 mutant survival and the synthesis of cell wall components are reinforced in the FKS1 mutant. Our results confirm that the FKS1 mutant has a β-1,3-glucan defect that affects the cell wall and partly elucidate the molecular mechanism responsible for cell wall synthesis. Our greater understanding of these mechanisms helps to explain how the FKS1 mutant survives, has useful implications for the study of similar pathways in other fungi, and increases the theoretical foundation for the regulation of the cell wall in S. cerevisiae.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA circNASP modulates the malignant behaviors in osteosarcoma via miR-1253/FOXF1 pathway

Highlights: • circNASP knockdown suppressed OS cell proliferation and invasion. • circNASP acted as a sponge of miR-1253 targeting FOXF1. • miR-1253 inhibitor reversed the effects of circNASP knockdown in OS cells. • circNASP modulated OS cell proliferation and invasion by miR-1253/FOXF1 pathway. Increasing evidences demonstrate that circular RNAs (circRNAs) serve as essential regulators in various human diseases, including cancer. However, the study on circRNA function in osteosarcoma (OS) is just emerging. In the present study, we screened out a novel circRNA termed circNASP which was significantly upregulated in OS tissues compared to adjacent normal tissues. We found that circNASP knockdown dramatically inhibited the proliferation, cell cycle progression and invasion of OS cells. Moreover, we showed that circNASP expression was positively correlated with tumor size and metastasis in OS patients. In terms of mechanism, we found that circNASP acts as a sponge of miR-1253 targeting FOXF1 in OS cells. By inhibiting miR-1253 availability, circNASP promoted FOXF1 expression. Rescue assays indicated that inhibition of miR-1253 could significantly reverse the effects of circNASP knockdown on OS cell proliferation and invasion while restoration of FOXF1 rescued the proliferation and invasion of OS cells transfected with miR-1253 mimics. Taken together, our findings demonstrated that circNASP contributes to malignant behaviors of OS cells by miR-1253/FOXF1 pathway, which suggested circNASP/miR-1253/FOXF1axis might be a potential therapeutic target.

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

Long non-coding RNA CASP5 promotes the malignant phenotypes of human glioblastoma multiforme

Highlights: • The expression of lncRNA CASP5 in GBM tissues was significantly higher than that in adjacent tissues. • LncRNA CASP5 promoted the proliferation of GBM cells both in vitro and in vivo. • LncRNA CASP5 facilitated the migration and invasion of GBM cells. Long non-coding RNAs (lncRNAs) have been demonstrated to be intensively involved in the development of various carcinomas, including glioblastoma multiforme (GBM). However, only a few of them have been well characterized. LncRNA CASP5 have been found to be up-regulated in GBM tissues compared with normal tissues in a microarray-based lncRNA profiling study. In the present study, we further explored the biological role of lncRNA CASP5 in GBM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA hsa{sub c}irc{sub 0}023404 exerts an oncogenic role in cervical cancer through regulating miR-136/TFCP2/YAP pathway

Cervical cancer (CC) is one of the most prevalent malignances among women. However, the mechanism underlying CC development remains elusive. Recently, circular RNAs (circRNAs) have been known as important regulators in tumorigenesis. Whether circRNAs are involved in CC requires to be determined. In the present study, we found that circRNA hsa{sub c}irc{sub 0}023404 was significantly upregulated in CC tissues compared to adjacent normal tissues. And its overexpression was correlated with poor prognosis in CC patients. Functionally, we showed that knockdown of hsa{sub c}irc{sub 0}023404 significantly suppressed the proliferation, arrested the cell-cycle progression and inhibited cell migration and invasion in CC. In terms of mechanism, we found that hsa{sub c}irc{sub 0}023404 acted as a sponge of miR-136 and miR-136 targeted TFCP2, which is an activator of YAP signaling pathway. We showed that hsa{sub c}irc{sub 0}023404 activated YAP pathway in CC via promoting TFCP2 expression by sponging miR-136, leading to CC development and progression. Taken together, our study for the first time demonstrated the pivot role of hsa{sub c}irc{sub 0}023404 and revealed a novel regulatory loop of hsa{sub c}irc{sub 0}023404/miR-136/TFCP2/YAP axis in CC progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Overexpressing circular RNA hsa{sub c}irc{sub 0}002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis

Circular RNAs (circRNAs) are a novel class of noncoding RNAs, whose importance in cancer has been gradually acknowledged. However, the functions of circRNAs in tumorigenesis have not been fully understood. In the present study, we identified a novel circRNA hsa{sub c}irc{sub 0}002052 significantly downregulated in osteosarcoma (OS) tissues and cell lines. Moreover, we found that hsa{sub c}irc{sub 0}002052 could act as a biomarker to indicate the prognosis of OS patients. Functionally, we showed that hsa{sub c}irc{sub 0}002052 overexpression significantly suppressed OS cell proliferation, migration and invasion while promoting apoptosis in vitro. Similarly, in vivo assay indicated that ectopic expression of hsa{sub c}irc{sub 0}002052 impaired OS cell growth. In terms of mechanism, we found that hsa{sub c}irc{sub 0}002052 inhibited miR-1205 while miR1205 targeted APC2, a negative regulator of Wnt/β-catenin signaling pathway. By releasing the inhibition of miR-1205 on APC2 expression, hsa{sub c}irc{sub 0}002052 suppressed the activation of Wnt/β-catenin signaling pathway, leading to attenuated OS progression. Taken together, our study for the first time revealed a suppressive circRNA hsa{sub c}irc{sub 0}002052 involved in OS progression. Our study suggested hsa{sub c}irc{sub 0}002052/miR-1205/APC2/Wnt/β-catenin axis might be a potential target for OS therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Identification and comparison of long non-conding RNA in Jinhua and Landrace pigs

Highlights: • The regulatory role of lncRNAs in fat deposition remains partially understood. • Investigation of lncRNAs expression level in intramuscular adipose tissues. • lncRNAs were implicated in pathways related to fat deposition and lipid metabolism. • A remarkable difference in fat metabolism in pigs. The regulatory role of long non-coding RNAs (lncRNAs) in various biological functions has been demonstrated. However, their role in fat deposition and lipid metabolism in pigs remains less understood. To explore the expression profile of lncRNAs in Jinhua and Landrace pigs, we investigated the expression levels of lncRNAs in intramuscular adipose tissues obtained from these pigs. Results showed that the expression levels of lncRNAs in these pig breeds significantly (Fold Change ≥ 2.0, FDR < 0.05) differed. A total of 4910 lncRNAs were identified, and 119 of these lncRNAs were differentially expressed. Of these differentially expressed lncRNAs, 60 and 59 were up- and down-regulated, respectively. The differentially expressed lncRNAs are involved in mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, PI3k-Akt signaling pathway. We then compared these differentially expressed lncRNAs with mRNAs and found that six of the co-expressed lncRNAs were implicated in pathways related to fat deposition and lipid metabolism. Overall, our results revealed a remarkable difference in fat metabolism in intramuscular adipose tissues of pigs, and provide a basis for subsequent research on fat deposition.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Knockdown of long noncoding RNA XIST alleviates oxidative low-density lipoprotein-mediated endothelial cells injury through modulation of miR-320/NOD2 axis

Highlights: • lncRNA XIST was upregulated in HUVECs stimulated by ox-LDL. • Knockdown of XIST boosted cell viability and suppressed cell apoptosis. • XIST regulated the expression of NOD2 by sponging miR-320. • XIST exerts its role via modulation of miR-320/NOD2 axis in ox-LDL-treated HUVECs. Atherosclerosis remains to be one of the most common vascular disorders resulting in morbidity and mortality in the world. Recent studies suggested that endothelial cells (ECs) injury caused by oxidative low-density lipoprotein (ox-LDL) is an early marker for atherosclerosis. Nevertheless, the mechanisms of ox-LDL-induced ECs injury are complicated and largely unknown. Here, we found lncRNA XIST (X-inactive specific transcript) was upregulated in human umbilical vein endothelial cells (HUVECs) stimulated by ox-LDL. Knockdown of XIST boosted the cell viability and suppressed cell apoptosis under ox-LDL stimuli. Further experiments identified XIST regulated the expression of Nucleotide-Binding Oligomerization Domain 2 (NOD2) by sponging miR-320. XIST silencing exerted a protective effect on ox-LDL-induced HUVECs injury via miR-320/NOD2 regulatory network. Our data provide insight into the role of the lncRNA XIST in ox-LDL mediated ECs injury, which can aid in developing new therapeutic strategies for the treatment of atherosclerosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA HIPK3 regulates human lens epithelial cells proliferation and apoptosis by targeting the miR-193a/CRYAA axis

Highlights: • CircRNA sequencing reveals 26 up-regulated and 75 down-regulated circRNAs in ARC. • CircHIPK3 is down-regulated in all three subtypes of ARC. • CircHIPK3 knockdown affects the cellular function in primary cultured HLECs. • CircHIPK3 exerts its role via modulation of circHIPK3/miR-193a/CRYAA axis in HLECs. Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated from back splicing. Accumulating evidence has demonstrated their vital regulation in several biological processes and ocular diseases. However, the role of circRNAs in age-related cataract (ARC), the leading cause of visual impairment worldwide, is still unknown. CircRNA sequencing reveals that 101 circRNAs are differentially expressed between the capsules of transparent and ARC lenses, including 75 down-regulated circRNAs and 26 up-regulated circRNAs transcripts. Eight of 10 differentially expressed circRNAs are further verified by quantitative RT-PCRs. One highly conserved circRNA, circHIPK3, is significantly down-regulated in all cortical, nuclear and posterior subcapsular subtypes of ARC. The silencing of circHIPK3, but not HIPK3 mRNA, significantly accelerates apoptosis development upon oxidative stress and decreases cell viability and proliferation in primary cultured human lens epithelial cells (HLECs). The expression of α-SMA and vimentin was downregulated, while the expression of E-cadherin and ZO-1was upregulated, suggesting the repression of epithelial-mesenchymal transition after circHIPK3 knockdown. CircHIPK3 silencing increases miR-193a expression. miR-193a regulates CRYAA expression by targeting the binding site within the 3′UTR. Moreover, miR-193a decreases the viability and proliferation, and increases the apoptosis of HLECs upon oxidative stress. This study suggests that circRNAs are the potential regulators in cataractogenesis. CircHIPK3 regulates HLECs function through miR-193a-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of ARC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long non-coding RNA KCNQ1OT1 modulates oxaliplatin resistance in hepatocellular carcinoma through miR-7-5p/ ABCC1 axis

Highlights: • KCNQ1OT1 was significantly up-regulated in oxaliplatin-resistant HCC cells. • Knockdown of KCNQ1OT1 inhibited the cell proliferation, migration, invasion. • KCNQ1OT1 modulated oxaliplatin resistance in HCC through miR-7-5p/ ABCC1 axis. The underlying functions of long non-coding RNAs (lncRNAs) on chemoresistance in multiple cancers have been testified. However, the function and mechanism of lncRNAs on chemoresistance in hepatocellular carcinoma are still confused. In this study, we concentrated on the function and mechanism of KCNQ1OT1 on oxaliplatin resistance in hepatocellular carcinoma. Results showed that KCNQ1OT1 was significantly up-regulated in oxaliplatin-resistant HepG2 and Huh7 cells. Moreover, knockdown of KCNQ1OT1 inhibited the cell proliferation, migration, invasion and reduced the expression of drug-resistant gene (MRP5, MDR1, LRP1). Additionally, bioinformatics analysis and dual-luciferase reporter assay showed that miR-7-5p directly targeted the 3′-UTR of miR-7-5p and ABCC1 mRNA, indicating that KCNQ1OT1 regulated the expression of ABCC1 via endogenous sponging miR-7-5p. Conclusively, KCNQ1OT1 modulated oxaliplatin resistance in hepatocellular carcinoma through miR-7-5p/ABCC1 axis, indicating a novel approach for the treatment of hepatocellular carcinoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA circ{sub 0}001649 acts as a prognostic biomarker and inhibits NSCLC progression via sponging miR-331-3p and miR-338-5p

Accumulating evidence documented the key functions of circular RNAs (circRNAs) in various malignancies. However, the study regarding the involvement of circRNAs in non-small cell lung cancer (NSCLC) has just begun. In the present study, qRT-PCR was used to determine the expression of circ{sub 0}001649 in NSCLC tissues and cells. Its clinical significance was further assessed by Fisher's exact test, Kaplan-Meier analysis and Cox regression model. Additionally, loss-of-function and gain-of-function experiments were carried out to detect the functional role of circ{sub 0}001649 in cell proliferation, migration and invasion. Furthermore, animal study was performed to confirm the in vitro results. Importantly, luciferase reporter assay was induced to reveal the underlying mechanism of circ{sub 0}001649. As a result, circ{sub 0}001649 was decreased in NSCLC tissues and cells and this downregulation is correlated with advanced TNM stage, positive lymph node metastasis and unfavorable prognosis. Additionally, circ{sub 0}001649 inhibited cell growth and metastasis both in vitro and in vivo. In mechanism, circ{sub 0}001649 was identified as the sponge of miR-331-3p and miR-338-5p. Moreover, the biological functions of circ{sub 0}001649 is partly dependent on its regulation on miR-331-3p and miR-338-5p. Collectively, this study suggested that circ{sub 0}001649/miR-331-3p/miR-338-5p regulatory signaling might be a potential target for NSCLC therapy.

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↗
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

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

The long noncoding RNA XIST protects cardiomyocyte hypertrophy by targeting miR-330-3p

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in numerous kinds of cardiovascular diseases, and their vital role in regulating cardiac hypertrophy still needs to be explored. In this study, we demonstrated that lncRNA X-inactive specific transcript (XIST) was upregulated in hypertrophic cardiac of mice and phenylephrine (PE)-treated cardiomyocytes. Next, we observed that inhibition of XIST induced hypertrophic response of cardiomyocyte and overexpression of XIST attenuated cardiomyocyte hypertrophy induced by PE. Furthermore, through online predictive tools and functional experiments, we demonstrated that XIST and S100B were targets of miR-330-3p. XIST and miR-330-3p suppressed each other in a reciprocal way in cardiomyocytes. Additionally, XIST promoted S100B expression through harboring the complementary binding sites with miR-330-3p, eventually prevented cardiac hypertrophy. In conclusion, our findings revealed a novel molecular mechanism that XIST/miR-330-3p/S100B pathway modulates the progression of cardiomyocyte hypertrophy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long non-coding RNA, Bmcob, regulates osteoblastic differentiation of bone marrow mesenchymal stem cells

Disordered osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) contributes to bone loss. The underlying mechanisms are complicated and not fully understood. Long non-coding RNAs (lncRNAs) are emerging as an important regulatory factors on bone metabolism. Here, we discovered a novel lncRNA, Bmcob, which modulated osteogenic differentiation of primary mouse BMSCs. Expression levels of Bmcob were significantly upregulated in early-to-mid stages during osteoblast differentiation. Silencing of Bmcob suppressed osteoblastic differentiation of BMSCs in vitro, whereas its overexpression protected BMSCs from oxidative stress induced inhibition on osteogenesis. Subsequently, we discovered that selenoprotein P (Sepp1), which is located next to the Bmcob gene, was partly responsible for the regulatory effects of Bmcob. In addition, a series of selenoproteins were downregulated in BMSCs with Bmcob knockdown. Mechanistically, we found Bmcob was associated with selenocysteine insertion sequence binding protein 2 (SBP2), a critical trans-acting factor for selenoprotein synthesis. Finally, we suggest an explanatory hypothesis that through modulating nucleocytoplasmic shuttling of SBP2, Bmcob regulates a number of selenoproteins expression, including sepp1, and then mediates osteogenesis of BMSCs. Taken together, our results revealed a novel mechanism regulating osteogenesis of BMSCs and may function as a potential target for treating osteoporosis.

60 APPLIED LIFE SCIENCES↗