scholarly journals Downregulated hsa_circ_005243 induced trophoblast cell dysfunction and inflammation via β-catenin and NF-κB pathways in gestational diabetes mellitus

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Wenbo Zhou ◽  
Guangtong She ◽  
Bin Yu ◽  
Lizhou Sun
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Inflammatory Factors ◽  
Migration Ability ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Gestational diabetes mellitus(GDM) is a common obstetric pregnancy complication, which poses a serious threat to the health of pregnant women and newborns. The specific etiology and pathogenesis of this disease have not been fully clarified, it is reported to be related with insulin resistance, inflammatory response and genetic factors etc. Circular RNA(circRNA) is a special kind of non-coding RNA, which have been attracted much attention in recent years. It has been reported that circRNAs may play a regulatory role in pregnancy-related diseases, including GDM. Methods: Previously we reported a circRNA, hsa_circ_005243, which was identified by RNA-sequencing. In this study we detected its expression in 20 GDM pregnant women and 20 normal controls using quantitative reverse transcription polymerase chain reaction analysis. Further in vitro experiments were conducted after hsa_circ_005243 knockdown in HTR8-S/Vneo cells, cell proliferation and migration ability was tested, the secretion of inflammatory factors (TNF-α and IL-6) were detected by ELISA. Then we detected the expression of β-catenin and increased nuclear factor kappa-B (NF-κB) signaling pathways which was related to GDM in the mechanism study. Results: We found the expression of hsa_circ_005243 was significantly reduced both in the placenta and plasma of GDM pregnant women. Knockdown of hsa_circ_005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) were observed after hsa_circ_005243 depletion. Further mechanism experiments showed that knockdown of hsa_circ_005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation. Conclusions: Collectively, our study showed that down-regulation of hsa_circ_005243 might be associated with the pathogenesis of GDM through regulating β-catenin and NF-κB signal pathways and suggest a new potential therapeutic target for GDM.

Downregulation of hsa_circ_005243 induces trophoblast cell dysfunction and inflammation via the β-catenin and NF-κB pathways in gestational diabetes mellitus

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Wenbo Zhou ◽  
Guangtong She ◽  
Bin Yu ◽  
Lizhou Sun
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Inflammatory Factors ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
And Migration ◽  
In Pregnancy ◽  
Proliferation And Migration

Abstract Background: Gestational diabetes mellitus (GDM) is a common complication in pregnancy that poses a serious threat to the health of both mother and child. While the specific etiology and pathogenesis of this disease are not fully understood, it is thought to arise due to a combination of insulin resistance, inflammation, and genetic factors. Circular RNAs (circRNAs) are a special kind of non-coding RNA that have attracted significant attention in recent years due to their diverse activities, including a potential regulatory role in pregnancy-related diseases, such as GDM. Methods: We previously reported the existence of a novel a circRNA, hsa_circ_005243, which was identified by RNA sequencing. In this study, we examined its expression in 20 pregnant women with GDM and 20 normal controls using quantitative reverse transcription PCR analysis. Subsequent in vitro experiments were conducted following hsa_circ_005243 knockdown in HTR-8/SVneo cells to examine the role of hsa_circ_005243 in cell proliferation and migration, as well as the secretion of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Finally, we examined the expression of β-catenin and nuclear factor kappa-B (NF-κB) signaling pathways to assess their role in GDM pathogenesis.Results: Expression of hsa_circ_005243 was significantly reduced in both the placenta and plasma of GDM patients. Knockdown of hsa_circ_005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) was observed after hsa_circ_005243 depletion. Further analyses showed that knockdown of hsa_circ_005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation. Conclusions: Downregulation of hsa_circ_005243 may be associated with the pathogenesis of GDM via the regulation of β-catenin and NF-κB signal pathways, suggesting a new potential therapeutic target for GDM.

scholarly journals Downregulation of hsa_circ_0005243 induces trophoblast cell dysfunction and inflammation via the β-catenin and NF-κB pathways

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Wenbo Zhou ◽  
Guangtong She ◽  
Bin Yu ◽  
Lizhou Sun
Keyword(s):  
Cell Proliferation ◽  
Nuclear Translocation ◽  
Inflammatory Factors ◽  
Pcr Analysis ◽  
Signal Pathways ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
And Migration ◽  
In Pregnancy ◽  
Proliferation And Migration

Abstract Background: Gestational diabetes mellitus (GDM) is a common complication in pregnancy that poses a serious threat to the health of both mother and child. While the specific etiology and pathogenesis of this disease are not fully understood, it is thought to arise due to a combination of insulin resistance, inflammation, and genetic factors. Circular RNAs (circRNAs) are a special kind of non-coding RNA that have attracted significant attention in recent years due to their diverse activities, including a potential regulatory role in pregnancy-related diseases, such as GDM. Methods: We previously reported the existence of a novel circRNA, hsa_circ_0005243, which was identified by RNA sequencing. In this study, we examined its expression in 20 pregnant women with GDM and 20 normal pregnant controls using quantitative reverse transcription PCR analysis. Subsequent in vitro experiments were conducted following hsa_circ_0005243 knockdown in HTR-8/SVneo cells to examine the role of hsa_circ_0005243 in cell proliferation and migration, as well as the secretion of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Finally, we examined the expression of β-catenin and nuclear factor kappa-B (NF-κB) signaling pathways to assess their role in GDM pathogenesis Results: Expression of hsa_circ_0005243 was significantly reduced in both the placenta and plasma of GDM patients. Knockdown of hsa_circ_0005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) was observed after hsa_circ_0005243 depletion. Further analyses showed that knockdown of hsa_circ_0005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation. Conclusions: Downregulation of hsa_circ_0005243 may be associated with the pathogenesis of GDM via the regulation of β-catenin and NF-κB signal pathways, suggesting a new potential therapeutic target for GDM.

scholarly journals lncRNA OR3A4 Promotes the Proliferation and Metastasis of Ovarian Cancer Through KLF6 Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangfang Guo ◽  
Jianan Du ◽  
Lingling Liu ◽  
Yawei Gou ◽  
Mingming Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Ovarian Tissue ◽  
Xenograft Model ◽  
Zebra Fish ◽  
Migration Ability ◽  
Cell Proliferation And Migration ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Proliferation And Migration

Aim: Ovarian cancer is a collaborative malignant tumor of the female reproductive system in clinical research. Some clinical studies have shown that OR3A4, which is a cancer-causing lncRNA, plays a major role in promoting the occurrence and development of a variety of tumors. And we also expressed the view that it expressed in ovarian tissue. However, the function of OR3A4 in ovarian cancer remains unclear.Methods and Results: To further verify the function of lncRNA OR3A4 in ovarian cancer, we established the xenograft model in the zebra fish. In this study, cells transformed with OR3A4 shRNA plasmids were transplanted into the zebra fish, and the cell proliferation and migration ability were significantly reduced compared to the empty vector. While knocking out OR3A4, we further downregulated its expression by siRNA of KLF6. Our study found that the knocked out OR3A4 resulted in a decrease in cell proliferation and migration level, which can be found in the downregulated expression of KLF6. We also verify the relationship between OR3A4 and circulating tumor cells in the zebra fish xenograft model, the results indicate that lncRNA OR3A4 may be involved in the resistance of ovarian cancer to complain.Conclusion: lncRNA OR3A4 promotes the proliferation and metastasis of ovarian cancer through the KLF6 pathway.

scholarly journals Long Non-Coding RNA DANCR Participates in the Regulation of Dexamethasone and Inflammation Factors on hASC Proliferation and Migration

2021 ◽  
Author(s):  
Ran Yan ◽  
Ping Dong ◽  
Zhigang Yang ◽  
Rui Cao ◽  
Xia Liu ◽  
...  
Keyword(s):  
Cell Counting ◽  
Inflammatory Factors ◽  
Dependent Manner ◽  
Migration Ability ◽  
Non Coding Rna ◽  
Tnf Α ◽  
The Mean ◽  
And Migration ◽  
Long Non Coding Rna ◽  
Proliferation And Migration

Abstract BackgroundBoth MSC and Dexamethasone are effective methods to treat inflammatory diseases, and they are likely to be used in combination. The proliferation and migration ability is one of the main biological characteristics of MSC for repairing. However, the effect of inflammatory factors and Dex on these characteristics of MSC has not been fully understood. Therefore, this study aimed to determine the role of lncRNA DANCR in hASC proliferation and migration regulation induced by Dex and inflammatory factors, to clarify the effect and mechanism of glucocorticoids on MSC's characteristics to participate in tissue repair in an inflammatory environment. MethodshASCs were cultured and treated with dexamethasone and inflammation factors, and cell proliferation, migration abilities, and lncRNA DANCR mRNA expression were detected. Additionally, to determine the roles and mechanisms, lncRNA DANCR was knockdown or overexpressed before Dex or TNF-α treatments. MSC proliferation was tested by cell counting kit-8 and cell cycle assay. MSC migration ability was analyzed by a scratching test. Moreover, proliferation and migration-related genes were measured by a reverse transcription-polymerase chain reaction. Nuclear factor-kB (NF-κB) and PI3K-AKT-mTOR pathway proteins were investigated by western blot analysis. All values are expressed as the mean ± standard error of the mean. The differences between the groups were assessed using a two-tailed Student’s t-test. ResultsDex decreased the proliferation and migration of hASC in a dose-dependent manner. Dex could upregulate the expression of lncRNA DANCR that inhibited hASC proliferation and migration. Knockdown of DANCR reversed the inhibition of hASC proliferation and migration induced by Dex. Moreover, DANCR was decreased by inflammatory cytokines, and overexpression of DANCR alleviated the promotion of hASC proliferation and migration induced by TNF-α. Furthermore, mechanistic investigation validated that DANCR was involved in the NF-κB signaling pathway. ConclusionsWe identified a lncRNA, DANCR, involved in Dex and inflammation-affected hASC proliferation and migration, thus suggesting that concurrent application of hASCs with steroids should be avoided in clinical settings. DANCR may serve as a promising approach to regulate stem cell characteristics under an inflamed microenvironment. These findings further enrich our understanding of the functional versatility of lncRNAs in the crosstalk of inflammation conditions and stem cells. Keywords： DANCR; long non-coding RNA; Dexamethasone; TNF-α; hASC; proliferation; migration

scholarly journals Expression and possible role of Smad3 in postnecrotizing enterocolitis stricture

2022 ◽  
Vol 5 (1) ◽  
pp. e000289
Author(s):  
Rui Chen ◽  
Chengjie Lv ◽  
Xiaoxia Zhao ◽  
Dong Ma ◽  
Dengming Lai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
Protein Expressions ◽  
Smad3 Protein ◽  
And Migration ◽  
Emt Markers ◽  
Tgf Β1 ◽  
Proliferation And Migration

ObjectiveTo investigate the expression of Smad3 (mothers against decapentaplegic homolog 3) protein in postnecrotizing enterocolitis stricture and its possible mechanism of action.MethodsWe used immunohistochemistry to detect the expression characteristics of Smad3 and nuclear factor kappa B (NF-κB) proteins in human postnecrotizing enterocolitis stricture. We cultured IEC-6 (crypt epithelial cells of rat small intestine) in vitro and inhibited the expression of Smad3 using siRNA technique. Quantitative PCR, western blotting, and ELISA were used to detect the changes in transforming growth factor-β1 (TGF-β1), NF-κB, tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and zonula occludens-1 (ZO-1) messenger RNA (mRNA) and protein expressions in IEC-6 cells. CCK8 kit and Transwell cellular migration were used to detect cell proliferation and migration. Changes in epithelial–mesenchymal transition (EMT) markers (E-cadherin and vimentin) in IEC-6 cells were detected by immunofluorescence technique.ResultsThe results showed that Smad3 protein and NF-κB protein were overexpressed in narrow intestinal tissues and that Smad3 protein expression was positively correlated with NF-κB protein expression. After inhibiting the expression of Smad3 in IEC-6 cells, the mRNA expressions of NF-κB, TGF-β1, ZO-1, and VEGF decreased, whereas the mRNA expression of TNF-α did not significantly change. TGF-β1, NF-κB, and TNF-α protein expressions in IEC-6 cells decreased, whereas ZO-1 and intracellular VEGF protein expressions increased. IEC-6 cell proliferation and migration capacity decreased. There was no significant change in protein expression levels of EMT markers E-cadherin and vimentin and also extracellular VEGF protein expression.ConclusionsWe suspect that the high expression of Smad3 protein in postnecrotizing enterocolitis stricture may promote the occurrence and development of secondary intestinal stenosis. The mechanism may be related to the regulation of TGF-β1, NF-κB, TNF-α, ZO-1, and VEGF mRNA and protein expression. This may also be related to the ability of Smad3 to promote epithelial cell proliferation and migration.

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