OBJECTIVE: To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR). METHODS: Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting. RESULTS: Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction. CONCLUSION Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.
Humans ; Aurora Kinase A/metabolism* ; Cell Line, Tumor ; Mitosis ; Cell Cycle ; Radiation, Ionizing ; RNA, Small Interfering/metabolism* ; Cyclin-Dependent Kinase Inhibitor p21/metabolism*

Objective To investigate the impacts of forkhead box M1(FOXM1)on the proliferation,invasion,and drug resistance of gastric cancer cells by regulating the circular RNA circ_NOTCH1.Methods Western blotting and real-time quantitative PCR were performed to determine the expression of FOXM1 protein and circ_NOTCH1,respectively,in the gastric cancer tissue,para-carcinoma tissue,human normal gastric mucosa epithelial cell line GES-1 and gastric cancer cell lines MGC-803,HGC-27,and BGC-823.BGC-823 cells were classified into the following groups:control,short hairpin RNA FOXM1(sh-FOXM1)and negative control(sh-NC),small interfering RNA circ_NOTCH1(si-circ_NOTCH1)and negative control(si-NC),and sh-FOXM1+circ_NOTCH1 overexpression plasmid(sh-FOXM1+pcDNA-circ_NOTCH1)and sh-FOXM1+negative control(sh-FOXM1+pcDNA).CCK-8 assay and clone formation assay were employed to measure the cell proliferation,and Transwell assay to measure cell invasion.After treatment with 1.0 mg/L adriamycin for 48 h,the cell resistance in each group was analyzed.Western blotting was employed to determine the expression levels of FOXM1,proliferating cell nuclear antigen(PCNA),Bax,multi-drug resistance-associated protein 1(MRP1),and multi-drug resistance gene 1(MDR1).RNA pull-down and RNA immunoprecipitation were employed to examine the binding of circ_NOTCH1 to FOXM1 protein.Results Compared with those in the para-carcinoma tissue,the expression levels of FOXM1 protein and circ_NOTCH1 in the gastric cancer tissue were up-regulated(all P<0.001).Compared with GES-1 cells,MGC-803,HGC-27,and BGC-823 cells showed up-regulated expression levels of FOXM1 protein and circ_NOTCH1(all P<0.001).Compared with the control group and sh-NC group,the sh-FOXM1 group with down-regulated expression of FOXM1 protein and circ_NOTCH1 showed decreased optical density value,clone formation rate,cell invasion number,and cell viability,down-regulated expression of PCNA,MRP1,and MDR1,and up-regulated expression of Bax protein in BGC-823 cells(all P<0.001).Compared with the control group and the si-NC group,the si-circ_NOTCH1 group with down-regulated expression of circ_NOTCH1 showed decreased optical density value,clone formation rate,cell invasion number,and cell viability,down-regulated expression of PCNA,MRP1,and MDR1,and up-regulated expression of Bax protein in BGC-823 cells(all P<0.001).Compared with sh-FOXM1 group and sh-FOXM1+pcDNA group,the sh-FOXM1+pcDNA-circ_NOTCH1 group with up-regulated expression of circ_NOTCH1 showed increased optical density value,clone formation rate,cell invasion number,and cell viability,up-regulated expression of PCNA,MRP1,and MDR1,and down-regulated expression of Bax protein(all P<0.001).FOXM1 protein was able to interact with circ_NOTCH1.Conclusion Interference with FOXM1 may inhibit the proliferation,invasion,and drug resistance of gastric cancer cells by silencing circ_NOTCH1 expression.
Humans ; bcl-2-Associated X Protein/metabolism* ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Drug Resistance ; Forkhead Box Protein M1/metabolism* ; Gene Expression Regulation, Neoplastic ; MicroRNAs/genetics* ; Proliferating Cell Nuclear Antigen/metabolism* ; Receptor, Notch1/metabolism* ; RNA, Small Interfering/genetics* ; Stomach Neoplasms/genetics*

Objective To investigate the effects of long noncoding RNA H19 on lipid accumulation of macrophages under high fat stress and its mechanism. Methods Human THP-1 cells-derived macrophages were incubated with ox-LDL, and the effects of H19 siRNA intervention on lipid accumulation was observed. The THP-1 cells were divided into control group (conventional culture), ox-LDL group, siRNA negative control (NC siRNA) combined with ox-LDL treatment group, and H19 siRNA combined with ox-LDL treatment group. Oil red O staining was used to determine the lipid accumulation in cells, and cholesterol concentration was analyzed by enzymatic method; ATP assay kit for detecting celluar ATP content; colorimetry was used to detect the levels of oxidative stress indicators and ELISA was used to detect the levels of monocyte chemoattractant protein-1 (MCP-1) in the cell supernatant. Western blot analysis was used to detect the protein expression of ATP binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear factor κB p-p65 (NF-κB p-p65). Results Knockdown H19 significantly inhibited intracellular lipid accumulation, decreased total cholesterol (TC) and cholesterol ester (CE) content, and decreased CE/TC ratio. Knockdown H19 significantly alleviated cell damage including an increase in ATP content, a decrease in oxidative stress levels and a decrease in MCP-1 levels, which caused by high-fat stress. H19 siRNA upregulated expression of ABCA1, PPARα and PGC-1α in THP-1 derived macrophages, downregulated NF-κB signal pathway. Conclusion Knockdown H19 upregulates PGC-1α expression in THP-1 cells and downregulates NF-κB pathway, which promotes cholesterol reverse transport, reduces inflammatory reaction and inhibits lipid accumulation.
Humans ; Adenosine Triphosphate ; Cholesterol ; NF-kappa B ; PPAR alpha ; RNA, Long Noncoding/genetics* ; RNA, Small Interfering/genetics* ; THP-1 Cells ; Macrophages/metabolism* ; Lipid Metabolism

OBJECTIVE: To demonstrate the mechanism of mechanical ventilation (MV) induced endoplasmic reticulum stress (ERS) promoting mechanical ventilation-induced pulmonary fibrosis (MVPF), and to clarify the role of angiotensin receptor 1 (AT1R) during the process. METHODS: The C57BL/6 mice were randomly divided into four groups: Sham group, MV group, AT1R-shRNA group and MV+AT1R-shRNA group, with 6 mice in each group. The MV group and MV+AT1R-shRNA group mechanically ventilated for 2 hours after endotracheal intubation to establish MVPF animal model (parameter settings: respiratory rate 70 times/minutes, tidal volume 20 mL/kg, inhated oxygen concentration 0.21). The Sham group and AT1R-shRNA group only underwent intubation after anesthesia and maintained spontaneous breathing. AT1R-shRNA group and MV+AT1R-shRNA group were airway injected with the adeno-associated virus one month before modeling to inhibit AT1R gene expression in lung tissue. The expressions of AT1R, ERS signature proteins [immunoglobulin heavy chain-binding protein (BIP), protein disulfide isomerase (PDI)], fibrosis signature proteins [collagen I (COL1A1), α-smooth muscle actin (α-SMA)] in lung tissues were detected by immunofluorescence and Western blotting. Hematoxylin-eosin (HE) staining was used to evaluate lung injury and Masson staining was used to evaluate pulmonary fibrosis. RESULTS: Compared with the Sham group, the degree of pulmonary fibrosis and lung injury were more significant in the MV group. In the MV group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were increased (AT1R/β-actin: 1.40±0.02 vs. 1, BIP/β-actin: 2.79±0.07 vs. 1, PDI/β-actin: 2.07±0.02 vs. 1, COL1A1/α-Tubulin: 2.60±0.15 vs. 1, α-SMA/α-Tubulin: 2.80±0.25 vs. 1, all P < 0.01). The number of E-cad⁺/AT1R⁺ and E-cad⁺/BIP⁺ cells in lung tissue increased, and the fluorescence intensity of COL1A1 and α-SMA increased. Compared with the MV group, the degree of pulmonary fibrosis and lung injury were significantly relieved in the MV+AT1R-shRNA group. In the MV+AT1R-shRNA group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were decreased (AT1R/β-actin: 0.53±0.03 vs. 1.40±0.02, BIP/β-actin: 1.73±0.15 vs. 2.79±0.07, PDI/β-actin: 1.04±0.07 vs. 2.07±0.02, COL1A1/α-Tubulin: 1.29±0.11 vs. 2.60±0.15, α-SMA/α-Tubulin: 1.27±0.10 vs. 2.80±0.25, all P < 0.01). The number of E-cad⁺/AT1R⁺ and E-cad⁺/BIP⁺ cells in lung tissue decreased, and the fluorescence intensity of COL1A1 and α-SMA decreased. There was no statistically significant difference in the indicators between AT1R-shRNA group and Sham group. CONCLUSIONS MV up-regulate the expression of AT1R in alveolar epithelial cells, activate the AT1R pathway, induce ERS and promote the progression of MVPF.
Mice ; Animals ; Pulmonary Fibrosis/chemically induced* ; Lung Injury ; Respiration, Artificial/adverse effects* ; Actins/metabolism* ; Tubulin ; Mice, Inbred C57BL ; Endoplasmic Reticulum Stress ; RNA, Small Interfering

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.
Humans ; Carcinoma, Renal Cell/pathology* ; Cell Proliferation ; Hypoxia ; Kidney Neoplasms ; MicroRNAs/genetics* ; Neoplasm Invasiveness/genetics* ; RNA, Circular/metabolism* ; RNA, Small Interfering ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics*

OBJECTIVE: To investigate the effect of inhibition of RAB27 protein family, which plays a pivotal role in exosome secretion, on biological behaviors of triple-negative breast cancer cells. METHODS: Quantitative real-time PCR and Western blotting were used to examine the expressions of RAB27 family and exosome secretion in 3 triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, and Hs578T) and a normal breast epithelial cell line (MCF10A). The effect of small interfering RNA (siRNA)-mediated silencing of RAB27a and RAB27b on exosome secretion in the 3 breast cancer cell lines was detected using Western blotting, and the changes in cell proliferation, invasion and adhesion were evaluated. RESULTS: Compared with normal breast epithelial cells, the 3 triple-negative breast cancer cell lines exhibited more active exosome secretion (P < 0.001) and showed significantly higher expressions of RAB27a and RAB27b at both the mRNA and protein levels (P < 0.01). Silencing of RAB27a in the breast cancer cells significantly down-regulated exosome secretion (P < 0.001), while silencing of RAB27b did not significantly affect exosome secretion. The 3 breast cancer cell lines with RAB27a silencing-induced down-regulation of exosome secretion showed obvious inhibition of proliferation, invasion and adhesion (P < 0.01) as compared with the cell lines with RAB27b silencing. CONCLUSION RAB27a plays central role in the exosome secretion in triple-negative breast cancer cells, and inhibiting RAB27a can inhibit the proliferation, invasion and adhesion of the cells.
Humans ; rab GTP-Binding Proteins/metabolism* ; Triple Negative Breast Neoplasms ; Cell Line, Tumor ; rab27 GTP-Binding Proteins/metabolism* ; RNA, Small Interfering/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic

OBJECTIVES: To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM). METHODS: The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α. RESULTS: Asiatic acid with the dose of 25 mg·kg^－1·d^－1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α. CONCLUSIONS Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.
Mice ; Animals ; Insulin Secretion ; Diabetes Mellitus, Type 2/drug therapy* ; Islets of Langerhans/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Insulin/therapeutic use* ; Diabetes Mellitus, Experimental ; Mice, Inbred ICR ; Glucose/therapeutic use* ; Interleukin-6/metabolism* ; RNA, Small Interfering/pharmacology* ; Adenosine Triphosphate ; GTP Phosphohydrolases/therapeutic use*

OBJECTIVES: To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice. METHODS: siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR. RESULTS: Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01). CONCLUSIONS The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.
Animals ; Female ; Mice ; Antioxidants/metabolism* ; Cholesterol/metabolism* ; Ethanol/pharmacology* ; Glutathione/pharmacology* ; Inflammation ; Lipids/pharmacology* ; Liver ; Malondialdehyde/pharmacology* ; Mice, Inbred C57BL ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; RNA, Small Interfering/pharmacology* ; Superoxide Dismutase ; Triglycerides/metabolism* ; Cytochrome P-450 CYP2E1/metabolism*

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.
Animals ; Mice ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics* ; Neuralgia ; RNA, Small Interfering ; Thalamus/metabolism* ; Up-Regulation

Objective: To identify the expression profile of circular RNA (circRNA) in placenta of pre-eclampsia (PE) pregnant women by high-throughput sequencing, and to construct the circRNA-microRNA (miRNA)-messenger RNA (mRNA) interaction network, so as to reveal the related pathways and regulatory mechanisms of PE. Methods: The clinical data and placentas of 42 women with PE (PE group) and 30 normal pregnant women (control group) who delivered in West China Second University Hospital from November 2019 to June 2021 were collected. (1) High-throughput sequencing was used to establish the differentially expressed circRNA profiles in placental tissues of 5 pairs of PE group and the control group. (2) Real-time quantitative PCR (qRT-PCR) was used to verify the expression levels of 6 differentially expressed circRNAs in placental tissues of PE group and control group. (3) Bioinformatics analysis was used to predict the target miRNA and analyze the co-expressed mRNA to construct a competitive endogenous RNA (ceRNA) network. The differentially expressed circRNAs were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. (4) Logistic regression analysis, Pearson correlation and Kendall's tau-b correlation analysis were used to test the correlation between the three differentially expressed circRNAs and the risk of PE and clinical characteristics. (5) circRNA_05393 was selected for subsequent functional study. Small interfering RNA (siRNA) and overexpression plasmid were used to knock down or increase the expression level of circRNA_05393 in trophoblast cell line HTR-8/SVneo cells, respectively. Transwell assay was used to detect the migration and invasion ability of the trophoblasts in vitro. Cell counting kit-8 assay was used to detect the proliferation ability of the trophoblasts. Results: (1) Seventy-two differentially expressed circRNAs were identified by high-throughput sequencing, of which 35 were up-regulated and 37 were down-regulated. (2) qRT-PCR showed that compared with the control group, circRNA_00673 (1.306±0.168 vs 2.059±0.242; t=2.356, P=0.021) and circRNA_07796 (1.275±0.232 vs 1.954±0.230; t=2.018, P=0.047) were significantly increased, while circRNA_05393 (1.846±0.377 vs 0.790±0.094; t=3.138, P=0.002) was significantly decreased. (3) The circRNA-miRNA-mRNA interaction network contained 3 circRNAs, 8 miRNAs and 53 mRNAs. GO functional annotation analysis showed that the biological process was mainly enriched in iron ion homeostasis, membrane depolarization during action potential and neuronal action potential. In terms of cellular components, they were mainly enriched in cytoskeleton and membrane components. In terms of molecular function, they were mainly enriched in the activity of voltage-gated sodium channel and basic amino acid transmembrane transporter. KEGG pathway enrichment analysis showed that mRNAs in the interaction network were mainly enriched in complement and coagulation cascade, glycine, serine and threonine metabolism, p53 signaling pathway and peroxisome proliferators-activated receptors (PPAR) signaling pathway. (4) Logistic regression analysis showed that down-regulation of circRNA_05393 expression was a risk factor for PE (OR=0.044, 95%CI: 0.003-0.596; P=0.019). Correlation analysis showed that circRNA_05393 was significantly correlated with systolic blood pressure and diastolic blood pressure in PE pregnant women (both P<0.05). (5) Knock down or overexpression of circRNA_05393 significantly reduced or increased the migration and invasion abilities of HTR-8/SVneo cells (all P<0.05), but had no significant effect on the ability of tube formation and proliferation (all P>0.05). Conclusions: The construction of circRNA expression profile in placenta and the exploration of circRNA-miRNA-mRNA interaction network provide the possibility to reveal the regulatory mechanism of specific circRNA involved in PE. Inhibition of circRNA_05393 may induce the progression of PE by reducing the migration and invasion of trophoblasts.
Female ; Humans ; Pregnancy ; MicroRNAs/metabolism* ; RNA, Circular/metabolism* ; RNA, Messenger/metabolism* ; Pre-Eclampsia/metabolism* ; Placenta/metabolism* ; RNA/metabolism* ; RNA, Small Interfering ; Gene Expression Profiling