المؤلفون: Ruiqin Cao, Tuanying Zhang, Xu Chen, Xinrong Yuan, Haifang Liu, Shuxiang Xu

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: 0301 basic medicine, Adult, Cell Survival, cervical cancer, Cell, Down-Regulation, Uterine Cervical Neoplasms, Apoptosis, Biology, migration, Flow cytometry, Cell Line, 03 medical and health sciences, 0302 clinical medicine, yes-associated protein 1, Downregulation and upregulation, Cell Movement, Cell Line, Tumor, microRNA, Genetics, medicine, Humans, Viability assay, cell viability, Adaptor Proteins, Signal Transducing, Aged, Cell Proliferation, YAP1, medicine.diagnostic_test, Oncogene, YAP-Signaling Proteins, General Medicine, Oncogenes, Articles, Cell cycle, Middle Aged, invasion, Up-Regulation, Gene Expression Regulation, Neoplastic, microRNA-15a-5p, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, 030220 oncology & carcinogenesis, Cancer research, Female, HeLa Cells, Transcription Factors

الوصف: MicroRNAs (miRNAs) have been reported to have important regulatory roles in the progression of several types of cancer, including cervical cancer (CC). However, the biological roles and regulatory mechanisms of miRNAs in CC remain to be fully elucidated. The aim of the present study was to examine the functions of miRNAs in CC and the possible mechanisms. Using a microarray, it was identified that miRNA-15a-5p (miR-15a-5p) was one of the most down-regulated miRNAs in CC tissues compared with adjacent noncancerous tissues. The low expression of miR-15a-5p was observed in CC tumor tissues with distant metastasis and in CC cell lines. In addition, the effects of miR-15a-5p upregulation on cell viability, apoptosis, invasion and migration of CC cells were investigated using CCK-8, flow cytometry, Transwell and wound healing assays, respectively. It was demonstrated that upregulation of miR-15a-5p significantly suppressed the viability, migration and invasion, and promoted the apoptosis of SiHa and C-33A cells. Furthermore, yes-associated protein 1 (YAP1), a well-known oncogene, was confirmed to be directly targeted by miR-15a-5p and was found to be negatively regulated by miR-15a-5p. Further correlation analysis indicated that miR-15a-5p expression was negatively correlated with YAP1 expression in CC tissues. Notably, overexpression of YAP1 abrogated the tumor suppressive effects of miR-15a-5p in CC cells. Taken together, these present findings indicated that the miR-15a-5p/YAP1 axis may provide a novel strategy for the clinical treatment of CC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::104a36d83b3a6022f8ff7c75723e79a2Test
http://europepmc.org/articles/PMC7447307Test

المؤلفون: Di You, Ye Tao, Hao‑Li Gong, Jiang‑Dong Ni, De‑Ye Song, Xin‑Zhan Mao

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Epithelial-Mesenchymal Transition, Adolescent, Cell, Apoptosis, Suppressor of cytokine signalling, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Suppressor of Cytokine Signaling 1 Protein, osteosarcoma, Cell Line, Tumor, Genetics, medicine, metastasis, Humans, DNA (Cytosine-5-)-Methyltransferases, Child, Neoplasm Staging, Suppressor of cytokine signaling 1, Chemistry, NF-kappa B, General Medicine, Transfection, Articles, Cell cycle, DNA methyltransferase 3B, Tumor Burden, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Cell Transformation, Neoplastic, nuclear factor-κB signalling pathway, Cell culture, 030220 oncology & carcinogenesis, embryonic structures, suppressor of cytokine signalling 1, Cancer research, Female, Signal transduction, microRNA-29a, Signal Transduction

الوصف: The present study aimed to investigate the roles of the microRNA‑29a/DNA methyltransferase 3B/suppressor of cytokine signalling 1 (miR‑29a/DNMT3B/SOCS1) axis in the invasion and the migration of osteosarcoma (OS). The expression levels of miR‑29a, DNMT3B and SOCS1 were determined in tissue samples and OS cell lines by reverse transcription‑quantitative polymerase chain reaction (PCR). Apoptosis was measured using flow cytometry analysis. Transwell and wound healing assays were conducted to measure the invasion and migration abilities of OS cells, respectively. A dual‑luciferase reporter assay was also conducted to determine the interaction between DNMT3B and miR‑29a, while methylation‑specific PCR was used to detect the methylation of SOCS1. Western blotting was performed to determine the protein levels of DNMT3B and SOCS1, as well as the levels of proteins associated with epithelial‑mesenchymal transition (EMT), apoptosis and the nuclear factor (NF)‑κB signalling pathway. The results demonstrated that miR‑29a and SOCS1 were downregulated, and DNMT3B was upregulated in both OS tissues and cell lines. The expression of miR‑29a and SOCS1 was found to be associated with advanced clinical stage and distant metastasis. In addition, the dual‑luciferase reporter assay revealed that DNMT3B was a direct target of miR‑29a. Overexpression using miR‑29a mimics decreased DNMT3B expression and the methylation level of SOCS1, which resulted in the upregulation of SOCS1 in U2OS and MG‑63 cells, while miR‑29a inhibition led to the opposite results. Transfection with miR‑29a mimics also promoted the apoptosis, and inhibited the invasion, migration and EMT process of OS cells, while it markedly reduced the nuclear translocation of p65 and IκB‑α degradation. Treatment with 5‑aza‑2'‑deoxycytidine worked together with miR‑29a mimics to synergistically enhance the aforementioned effects. By contrast, the effects induced by miR‑29a were partly reversed upon co‑transfection with SOCS1 siRNA. In conclusion, miR‑29a promoted the apoptosis, and inhibited the invasion, migration and EMT process of OS cells via inhibition of the SOCS1/NF‑κB signalling pathway by directly targeting DNMT3B.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f9b2293da7bf0618d35b3665496f0d67Test
http://europepmc.org/articles/PMC6713425Test

المؤلفون: Dong Shuanghai, Tian Jiwei, Xia Tian

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: phosphatase and tensin homolog, Adult, Male, 0301 basic medicine, Bone sialoprotein, human adipose-derived mesenchymal stem cells, Blotting, Western, Osteocalcin, Core Binding Factor Alpha 1 Subunit, 03 medical and health sciences, 0302 clinical medicine, Osteogenesis, Genetics, Animals, Humans, PTEN, Tensin, Osteopontin, Protein kinase B, beta Catenin, biology, Chemistry, Mesenchymal stem cell, PTEN Phosphohydrolase, AKT/β-catenin signaling pathway, Cell Differentiation, Mesenchymal Stem Cells, Articles, differentiation, General Medicine, Middle Aged, Alkaline Phosphatase, Cell biology, microRNA-29b, RUNX2, MicroRNAs, 030104 developmental biology, Adipose Tissue, 030220 oncology & carcinogenesis, biology.protein, Female, Signal transduction, Proto-Oncogene Proteins c-akt

الوصف: Accumulating evidence has documented that microRNAs (miRNAs or miRs) function as important post‑transcriptional regulators of the differentiation of mesenchymal stem cells (MSCs), including human adipose‑derived mesenchymal stem cells (hADSCs); however, their roles in hADSC osteogenic differentiation require further investigation. The present study aimed to investigate the role of miRNAs in the osteogenic differentiation of hADSCs and to elucidate the underlying molecular mechanisms. Using an miRNA microarray, it was found that 24 miRNAs were upregulated and 14 miRNAs were downregulated compared with the undifferentiated cells, and miR‑29b‑3p (miR‑29b) was selected for further experiments. Functional experiments revealed that the upregulation of miR‑29b by agomir‑29b significantly enhanced alkaline phosphatase (ALP) activity and the mineralization of extracellular matrix (ECM), and led to an increase in the mRNA and protein levels of osteogenic marker genes, including runt‑related transcription factor 2 (Runx2), osteopontin (OPN), osteocalcin (OCN) and bone sialoprotein (BSP), whereas the knockdown of miR‑29b suppressed these processes. In addition, phosphatase and tensin homolog (PTEN), a negative regulator of the AKT/β‑catenin pathway, was identified as a direct target of miR‑29b in the hADSCs. Moreover, it was observed that the overexpression of miR‑29b activated the AKT/β‑catenin signaling pathway by inhibiting PTEN expression in the hADSCs. Most importantly, it was also found that the overexpression of PTEN reversed the promoting effects of miR‑29b on osteogenic differentiation. On the whole, these findings suggest that miR‑29b promotes the osteogenic differentiation of hADSCs by modulating the PTEN/AKT/β‑catenin signaling pathway. Thus, this miRNA may be a promising target for the active modulation of hADSC‑derived osteogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c549ad6faf5c11de99d92315d32ff1eeTest
https://doi.org/10.3892/ijmm.2020.4615Test

المؤلفون: Peng Jin, Xiaojing Wu, Junhao Hu, Qi Zhou, Wei Zheng

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: 0301 basic medicine, Senescence, Adult, Male, medicine.medical_specialty, Aging, Cell, Down-Regulation, Coronary Artery Disease, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Internal medicine, Genetics, medicine, Humans, IGFBP1, Protein kinase B, Coronary atherosclerosis, Cells, Cultured, Cellular Senescence, Aged, Aged, 80 and over, Oncogene, business.industry, Endothelial Cells, General Medicine, Articles, Middle Aged, Atherosclerosis, Molecular medicine, Coronary Vessels, Up-Regulation, Insulin-Like Growth Factor Binding Protein 1, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, cell senescence, 030220 oncology & carcinogenesis, Female, business, Jagged-1 Protein, Signal Transduction

الوصف: The senescence of vascular endothelial cells (ECs) plays a critical role in aging-related cardiovascular diseases. We previously reported the causal relation of Jagged1 in ECs and the thickening of the arterial wall in aging mice. The aim of the present study was to further investigate the correlation between insulin-like growth factor-binding protein 1 (IGFBP1), one of the secretory proteins regulated by Jagged1, and the severity of coronary atherosclerosis and patient age, as well as its effect on EC senescence. First, microarray analysis was performed to screen the differentially expressed genes regulated by Jagged1 in human coronary arterial ECs (HCAECs). Inhibition of the Jagged1 expression using a small interfering RNA knockdown method in HCAECs led to the upregulation of 17 and the downregulation of 78 genes by >3-fold, and IGFBP1 was confirmed to be a secretory protein expressed by HCAECs and regulated by Jagged1. Subsequently, in 112 consecutively enrolled patients with acute chest pain who underwent coronary angiography, the circulating level of IGFBP1 was found to be positively correlated with age (r=0.512, P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e60f42ffd56ce1646f179f09fed4c87Test
http://europepmc.org/articles/PMC6777673Test

المؤلفون: Xiaoping Li, Qiongying Wei, Dan Xue, Tingyan Lin, Ping Yang, Lan Lin

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Lung Neoplasms, Cell, Apoptosis, B7-H1 Antigen, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Western blot, Cell Movement, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Genetics, medicine, Humans, Lung cancer, Wnt Signaling Pathway, non-small cell lung cancer, beta Catenin, Cell Proliferation, A549 cell, Oncogene, medicine.diagnostic_test, Chemistry, Cell growth, Interleukins, interleukin-21, Wnt signaling pathway, Interleukin-21 Receptor alpha Subunit, Articles, General Medicine, Middle Aged, Cell cycle, invasion, medicine.disease, Up-Regulation, programmed death 1 ligand 1, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, A549 Cells, 030220 oncology & carcinogenesis, Cancer research, Female

الوصف: Lung cancer is considered to be one of the world's deadliest diseases, with non‑small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. The present study aimed to investigate the role and underlying mechanisms of interleukin‑21 (IL‑21), and its receptor IL‑21R, in NSCLC. Lung tissues and blood samples of NSCLC were used to measure IL‑21, IL‑21R and programmed death 1 ligand 1 (PD‑L1) expression using ELISA, western blot and immunohistochemistry analyses. Following treatment with different doses of IL‑21, the proliferation, invasion and migration of human NSCLC cell line A549 was evaluated using a cell counting kit‑8, colony formation, Transwell and scratch wound healing assays, respectively. Additionally, IL‑21R and PD‑L1 expression in A549 cells was detected using western blot analysis and immunofluorescence. IL‑21R silencing was subsequently used to investigate its effects in cell proliferation, invasion and migration. PD‑L1, IL‑1β and tumor necrosis factor α (TNF‑α) expression were measured. Finally, Wnt/β‑catenin signaling expression was evaluated using western blot analysis following treatment with IL‑21. Cells were then treated with lithium chloride (LiCl), which is an agonist of Wnt/β‑catenin signaling, and the levels of PD‑L1, IL‑1β and TNF‑α were detected. The results revealed that IL‑21 and IL‑21R expression in the lung tissues and blood samples of patients with NSCLC were decreased, while PD‑L1 expression was increased, compared with normal tissues or healthy controls. Treatment of A549 cells with IL‑21 upregulated IL‑21R expression, downregulated PD‑L1 and inhibited cell growth and metastasis in a dose‑dependent manner. Following IL‑21R silencing, the effects of IL‑21 treatment were reversed, suggesting that IL‑21 acted on A549 cells through binding to IL‑21R. In addition, the results demonstrated that IL‑21 treatment reduced the expression levels of proteins associated with the Wnt/β‑catenin signaling, whereas activation of Wnt/β‑catenin signaling with the LiCl agonist upregulated PD‑L1, IL‑1β and TNF‑α expression. In conclusion, the IL‑21/IL‑21R axis reduced the growth and invasion of NSCLC cells via inhibiting Wnt/β‑catenin signaling and PD‑L1 expression. The present results may provide a novel molecular target for NSCLC diagnosis and therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5996935d1b3f6f5479dc00faf3d6db8Test
https://doi.org/10.3892/ijmm.2019.4354Test

المؤلفون: Peter Schirmacher, Erzsébet Valicsek, Jörg Kriegsmann, Marcus Renner, Farkas Sükösd, László Tiszlavicz, Christoph Mader, Csaba Tóth, Esther Herpel

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: 0301 basic medicine, Oncology, Male, Colorectal cancer, DNA Mismatch Repair, Metastasis, 0302 clinical medicine, Tubulin, PMS2, Tissue microarray, MMR proteins, Liver Neoplasms, General Medicine, Articles, Middle Aged, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, ribonucleoside-diphosphate reductase 1, Female, Colorectal Neoplasms, Signal Transduction, Adult, medicine.medical_specialty, Ribonucleoside Diphosphate Reductase, apoptosis repressor protein, colorectal cancer, Nerve Tissue Proteins, Biology, 03 medical and health sciences, excision repair cross-complementing 1, Internal medicine, Cell Line, Tumor, Genetics, medicine, Humans, Aged, Tumor Suppressor Proteins, Cancer, class III β-tubulin, medicine.disease, Endonucleases, MSH6, liver metastasis, Cytoskeletal Proteins, 030104 developmental biology, MSH2, Cancer research, ERCC1, Tumor Suppressor Protein p53, Biomarkers

الوصف: Liver metastasis in colorectal cancer is common and the primary treatment is chemotherapy. To date, there is no routinely used test in clinical practice to predict the effectiveness of conventional chemotherapy. Therefore, biomarkers with predictive value for conventional chemotherapy would be of considerable benefit in treatment planning. We analysed three proteins [excision repair cross-complementing 1 (ERCC1), ribonucleoside-diphosphate reductase 1 (RRM1) and class III β-tubulin (TUBB3)] in colorectal cancer liver metastasis. We used tissue microarray slides with 101 liver metastasis samples, stained for ERCC1, RRM1 and TUBB3 and established scoring systems (fitted for tissue microarray) for each protein. In statistical analysis, we compared the expression of ERCC1, RRM1 and TUBB3 to mismatch proteins (MLH1, MSH2, MSH6 and PMS2), p53 and to apoptosis repressor protein (ARC). Statistically significant correlations were found between ERCC1, TUBB3 and MLH1, MSH2 and RRM1 and MSH2, MSH6. Noteworthy, our analysis revealed a strong significant correlation between cytoplasmic ARC expression and RRM1, TUBB3 (p=0.000 and p=0.001, respectively), implying an additional role of TUBB3 and RRM1 not only in therapy resistance, but also in the apoptotic machinery. Our data strengthens the importance of ERCC1, TUBB3 and RRM1 in the prediction of chemotherapy effectiveness and suggest new functional connections in DNA repair, microtubule network and apoptotic signaling (i.e. ARC protein). In conclusion, we showed the importance and need of predictive biomarkers in metastasized colorectal cancer and pointed out the relevance not only of single predictive markers but also of their interactions with other known and newly explored relations between different signaling pathways.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa747ca1fd0573029a75be591a337ffdTest
http://europepmc.org/articles/PMC5627886Test

المؤلفون: Jing Chen, Li Tang, Fu-Gang Han, Ye Xin, Dong Chen, Wen Wen

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: 0301 basic medicine, MAPK/ERK pathway, Adult, Male, Lipopolysaccharide, MAP Kinase Signaling System, Inflammation, Gene Expression Regulation, Enzymologic, Small hairpin RNA, Rats, Sprague-Dawley, sepsis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Downregulation and upregulation, Genetics, medicine, Animals, Humans, myocardial injury, miR-101-3p, Oncogene, Myocardium, dual specificity phosphatase-1, NF-kappa B, NF-κB, Dual Specificity Phosphatase 1, General Medicine, Articles, Middle Aged, Rats, Up-Regulation, MicroRNAs, 030104 developmental biology, chemistry, Apoptosis, inflammation, 030220 oncology & carcinogenesis, Cancer research, Female, medicine.symptom

الوصف: Numerous studies have found that microRNAs (miRNAs or miRs) are aberrantly expressed when sepsis occurs. The present study aimed to investigate the role of miR‑101‑3p in sepsis‑induced myocardial injury and to elucidate the underlying mechanisms. Models of myocardial injury were established both in vivo and in vitro. The results revealed that miR‑101‑3p was upregulated in the serum of patients with sepsis‑induced cardiomyopathy (SIC) and positively correlated with the levels of pro‑inflammatory cytokines (including IL‑1β, IL‑6 and TNF‑α). Subsequently, rats were treated with miR‑101‑3p inhibitor to suppress miR‑101‑3p and were then exposed to lipopolysaccharide (LPS). The results revealed that LPS induced marked cardiac dysfunction, apoptosis and inflammation. The inhibition of miR‑101‑3p markedly attenuated sepsis‑induced myocardial injury by attenuating apoptosis and the expression of pro‑inflammatory cytokines. Mechanistically, dual specificity phosphatase‑1 (DUSP1) was found to be a functional target of miR‑101‑3p. The downregulation of miR‑101‑3p led to the overexpression of DUSP1, and the inactivation of the MAPK p38 and NF‑κB pathways. Moreover, blocking DUSP1 by short hairpin RNA against DUSP1 (sh‑DUSP1) significantly reduced the myocardial protective effects mediated by the inhibition of miR‑101‑3p. Collectively, the findings of the present study demonstrate that the inhibition of miR‑101‑3p exerts cardioprotective effects by suppressing MAPK p38 and NF‑κB pathway activation, and thus attenuating inflammation and apoptosis dependently by enhancing DUSP1 expression.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a4748ea43d7de898cefe7476347ae29Test
https://pubmed.ncbi.nlm.nih.gov/33448324Test

المؤلفون: Lihong Zhu, Shumei Yang, Jianfeng Wang

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: Adult, 0301 basic medicine, cervical cancer, Cell, Down-Regulation, Uterine Cervical Neoplasms, Apoptosis, Cell Line, Flow cytometry, HeLa, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Cell Line, Tumor, Genetics, medicine, Humans, Neoplasm Invasiveness, Viability assay, Protein kinase A, microRNA-217, Mitogen-Activated Protein Kinase 1, biology, medicine.diagnostic_test, Chemistry, Kinase, Cell Cycle, Articles, General Medicine, Middle Aged, Cell cycle, biology.organism_classification, Molecular biology, Up-Regulation, Gene Expression Regulation, Neoplastic, MicroRNAs, HEK293 Cells, 030104 developmental biology, medicine.anatomical_structure, phosphorylated extracellular signal-regulated kinase 1/2/extracellular signal-regulated kinase 1/2, 030220 oncology & carcinogenesis, Female, HeLa Cells

الوصف: MicroRNA (miR)-217 serves a pivotal role in the progression of colorectal cancer, renal cell carcinoma and glioma, however, the role of miR-217 in cervical cancer (CC) remains unclear. In the present study, the mechanism of miR-217 in cervical cancer was explored. The mRNA expression of miR-217 and mitogen-activated protein kinase 1 (MAPK1) were assessed using reverse transcription-quantitative polymerase chain reaction analysis. Cell Counting-Kit 8, wound-healing and Transwell assays were performed to detect cell viability, migration and invasion, respectively. Apoptosis and cell cycle were determined by flow cytometry. TargetScan 7.2 and dual-luciferase reporter assays were respectively used to determine miR-217 target genes and their binding capacities. The protein expression levels of MAPK1, phosphorylated (p)-extracellular signal-regulated kinase 1/2 (ERK1/2)/ERK1/2, Bcl-2, Bax and cleaved caspase-3 were quantified by western blotting. It was found that miR-217 was downregulated in patients with CC and in CC cells. The viability, migration and invasion of cells were suppressed by a miR-217 mimic. It was also found that apoptosis was increased and cell cycle was inhibited by the miR-217mimic, which was supported by changes in Bcl-2, Bax and cleaved caspase-3. MAPK1 was upregulated in patients with CC and was a target gene of miR-217. MAPK1 reversed the inhibition of miR-217 on cell viability, migration, invasion and apoptosis. The protein levels of MAPK1 and p-ERK1/2, which were higher in the mimic MAPK1 group than those in the control or mimic groups, were ameliorated by PD98059. The results of the present study demonstrated that miR-217 had an anti-CC effect and may be effectively used in the treatment of CC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a7665bff665862df46d21995301acee2Test
https://doi.org/10.3892/ijmm.2019.4328Test

المؤلفون: Pengyun Li, Zhan Zhang, Huan Yan, Yan Wang

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: 0301 basic medicine, Adult, Receptors, CXCR4, Cell, migration, 03 medical and health sciences, Cell Movement, Pregnancy, Genetics, Trophoblast cell migration, medicine, Humans, CXC chemokine receptors, RNA, Messenger, Gene knockdown, hypoxia-inducible factor-1α, Chemistry, hypoxia, Trophoblast, Placentation, General Medicine, Transfection, Articles, invasion, Hypoxia-Inducible Factor 1, alpha Subunit, trophoblast cells, Cell Hypoxia, Cell biology, Trophoblasts, Pregnancy Trimester, First, 030104 developmental biology, medicine.anatomical_structure, CXC chemokine receptor 4, Gene Knockdown Techniques, Cancer cell, embryonic structures, Female

الوصف: The placenta initially develops in a low‑oxygen environment up to week 8‑10 of gestation, and a low oxygen level is a critical factor in the regulation of trophoblast migration and invasion. CXC chemokine receptor 4 (CXCR4) is transcriptionally activated by hypoxia in cancer cells. However, whether CXCR4 is involved in hypoxia‑inducible factor (HIF)‑1α‑dependent trophoblastic migration and invasion in a physiologically hypoxic environment (3% O2) remains to be fully elucidated and requires further investigation. In the present study, the expression of CXCR4 in first‑trimester villi was investigated, as was the response of the trophoblast to hypoxia, and the role of CXCR4 and HIF‑1α in trophoblast migration and invasion. CXCR4 was significantly elevated in the first‑trimester villi compared with normal full‑term placentas. In vitro, the expression of CXCR4 at the mRNA and protein levels was increased in JEG3 cells exposed to 3% O2 in a time‑dependent manner, and the migratory and invasive abilities of the JEG3 cells were upregulated. In addition, CXCR4 knockdown by transfection with CXCR4‑specific small interfering (si)RNA decreased the migration and invasion of JEG3 cells exposed to 3% O2. Furthermore, synthetic siRNA specific for HIF‑1α significantly suppressed the expression of CXCR4 in JEG3 cells exposed to 3% O2, whereas pcDNA‑HIF‑1α significantly increased the expression of CXCR4. These results indicated that the hypoxia‑induced expression of CXCR4 promoted trophoblast cell migration and invasion via the activation of HIF‑1α, which is crucial during placentation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7fa5cda22f32d48f98449172d189ec17Test
http://europepmc.org/articles/PMC6089771Test

المؤلفون: Tonghang Guo, Che Xiaoyan, Xiaohua Jiang, Xu Zhipeng, Liu Wang, Huan Zhang, Wen Yu, Guixiang Zhou, Dexin Yu, Guangyuan Li, Furhan Iqbal, Yuanwei Zhang, Liang Shi

المصدر: International Journal of Molecular Medicine

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Transcriptional Activation, Karyotype, Down-Regulation, Chromosomal translocation, Spermatocyte, Biology, Translocation, Genetic, chromosomal translocation, 03 medical and health sciences, Meiotic Prophase I, 0302 clinical medicine, Meiosis, Spermatocytes, transcriptional inactivation, Testis, Genetics, Homologous chromosome, medicine, Humans, DNA Breaks, Double-Stranded, Spermatogenesis, Azoospermia, Chromosomes, Human, X, 030219 obstetrics & reproductive medicine, Chromosomes, Human, Y, synaptonemal complex, Synapsis, Chromosome Breakage, General Medicine, Articles, Molecular biology, recombination, 030104 developmental biology, medicine.anatomical_structure, Chromosomes, Human, Pair 1, Chromosome breakage, infertility

الوصف: Balanced translocations are known to be associated with infertility, spontaneous abortions and birth defects in mammals. Spermatocyte spreading and immunostaining were applied to detect meiotic prophase I progression, homologous chromosome pairing, synapsis and recombination in an azoospermic reciprocal translocation 46,X,t(Y;1)(p11.3;p31) carrier. Histological examination of testicular sections revealed a severely reduced number of germ cells with no spermatids or sperm in the carrier. A significant reduction in XY recombination was observed in the patient. The number of MLH1 foci on autosomes that are not involved in the translocation per cell was also significantly decreased in our patient as compared to the controls, which indicates an inter-chromosomal effect (ICE) of the translocation on recombination. An increase in leptotene (P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b73fe1532cab38509642b90e45069470Test
http://europepmc.org/articles/PMC5504999Test