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1.
Int J Med Sci ; 15(2): 142-152, 2018.
Article in English | MEDLINE | ID: mdl-29333098

ABSTRACT

Background: MicroRNAs (miRNAs) are non-coding small RNAs that function as negative regulators of gene expression and are involved in tumour biology. The eIF4E-binding proteins (eIF4EBPs) play essential roles in preventing translation initiation and inhibiting protein synthesis at a global or message-specific level in a variety of tumours. Methods: According to comparative miRNA profiles of clinical cervical cancer and non-cancerous cervical tissue specimens, several miRNAs were aberrantly expressed in the cervical cancer samples. C33a and SiHa cell proliferation and apoptosis were detected using methyl thiazolyl tetrazolium (MTT) and flow cytometry assays, respectively. Results: Among the aberrantly expressed miRNAs, miR-22-3p was significantly differentially expressed in cervical cancer tissues and was highly associated with cervical cancer cell growth regulation. In addition, bioinformatic predictions and experimental validation were used to identify whether eIF4E-binding protein 3 (eIF4EBP3) was a direct target of miR-22-3p; eIF4EBP3 protein levels were generally low in the cervical cancer tissues. Furthermore, functional studies revealed that either a miR-22-3p inhibitor or eIF4EBP3 overexpression could induce apoptosis in cervical cancer cells in vitro. Importantly, we found that eIF4EBP3 accumulation could significantly attenuate cervical cancer cell proliferation triggered by a miR-22-3p mimic as well as enhance apoptosis in cervical cancer cells. Conclusion: Taken together, our data provide primary proof that miR-22-3p can induce cervical cancer cell growth at least in part by up-regulating its expression to decrease eIF4EBP3 expression levels; miR-22-3p thus holds promise as a prognostic biomarker and potential therapeutic target for treating cervical cancer.


Subject(s)
Carcinoma, Squamous Cell/pathology , Carrier Proteins/genetics , MicroRNAs/genetics , Uterine Cervical Neoplasms/pathology , Adult , Apoptosis/genetics , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Uterine Cervical Neoplasms/genetics
2.
J Cell Mol Med ; 21(10): 2412-2425, 2017 10.
Article in English | MEDLINE | ID: mdl-28393453

ABSTRACT

Clinical pregnancies increasingly end in recurrent miscarriage (RM) during the first trimester, with genetic factors shouldering the main responsibility. MicroRNAs (miRNAs) regulate gene expression in a wide array of important biological processes. We examined the potential role of dysregulated miRNAs in RM pathogenesis and trophoblast development as an approach to elucidate the molecular mechanism behind RM. miRNA profiles from clinical specimens of RM and induced abortion (IA) were compared, and several miRNAs were found to be aberrantly expressed in RM samples. Among the miRNAs, miR-365 was significantly differentially expressed in RM decidual tissues. Furthermore, our results demonstrate that miR-365 functions as an upstream regulator of MDM2/p53 expression, cell cycle progression and apoptosis in trophoblasts. Bioinformatic prediction and experimental validation assays identified SGK1 as a direct target of miR-365; consistently, its protein levels were low in decidual tissues. Additionally, functional studies revealed that SGK1 silencing elicits cell cycle arrest and apoptosis in trophoblasts and that SGK1 overexpression attenuates the effects of miR-365 on apoptosis and MDM2/p53 expression. Collectively, our data provide evidence that the up-regulation of miR-365 may contribute to RM by decreasing SGK1 expression, which suggests its potential utility as a prognostic biomarker and therapeutic target for RM.


Subject(s)
Abortion, Habitual/genetics , Apoptosis/genetics , Gene Expression Regulation , MicroRNAs/genetics , Trophoblasts/metabolism , 3' Untranslated Regions/genetics , Abortion, Induced , Adult , Cell Cycle Checkpoints/genetics , Cell Line , Female , Gene Expression Profiling/methods , Humans , Immediate-Early Proteins/genetics , Immediate-Early Proteins/metabolism , Microscopy, Electron, Transmission , Pregnancy , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , RNA Interference , Trophoblasts/ultrastructure
3.
Cell Physiol Biochem ; 36(6): 2418-32, 2015.
Article in English | MEDLINE | ID: mdl-26279444

ABSTRACT

BACKGROUND/AIMS: The purpose of this study was to investigate the relationships among exposure to coplanar polychlorinated biphenyls (Co-PCBs), the expression of gC1qR and the underlying intracellular apoptotic signaling pathways of human extravillous cytotrophoblast (EVCT)-derived transformed cells (HTR-8/SVneo and HPT-8). METHODS: Apoptosis in HTR-8/SVneo and HPT-8 cells was assessed using flow cytometric analysis. gClqR expression was examined in the HTR-8/SVneo and HPT-8 cells using real-time qPCR and western blot analyses. The phosphorylations of p38 mitogen-activated protein kinase (p38 MAPK) (Thr180/Tyr182) and extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Thr204) were detected using western blot analyses. RESULTS: The HTR-8/SVneo and HPT-8 cells treated with Co-PCBs exhibited significantly increased gClqR expression, p38 MAPK/ERK activation and an up-regulation of cellular apoptosis. These effects were abrogated by the application of gC1qR small interfering RNA (siRNA). Furthermore, apoptosis in HTR-8/SVneo and HPT-8 cells was observed upon treatment with Co-PCBs, and these effects were reversed by the p38 MAPK pathway inhibitor SB203580 or the ERK1/2 pathway inhibitor PD098059. CONCLUSION: These data support a mechanism wherein gC1qR plays a crucial p38 MAPK/ERK signaling pathway-dependent role in Co-PCBs-induced apoptosis of human EVCT-derived transformed cells.


Subject(s)
Apoptosis/drug effects , Polychlorinated Biphenyls/pharmacology , Trophoblasts/cytology , Trophoblasts/enzymology , p38 Mitogen-Activated Protein Kinases/metabolism , Carrier Proteins/metabolism , Cell Line, Transformed , Extracellular Signal-Regulated MAP Kinases/metabolism , Flavonoids/pharmacology , Gene Silencing/drug effects , Humans , Imidazoles/pharmacology , MAP Kinase Signaling System/drug effects , Mitochondrial Proteins/metabolism , Pyridines/pharmacology , Trophoblasts/drug effects
4.
J Transl Med ; 11: 118, 2013 May 08.
Article in English | MEDLINE | ID: mdl-23651874

ABSTRACT

BACKGROUND: Human papillomavirus type 16 (HPV 16) E2 protein is a multifunctional DNA-binding protein. HPV 16 E2 regulates many biological responses, including DNA replication, gene expression, and apoptosis. The purpose of this study was to investigate the relationship among the receptor for globular heads of the human C1q (gC1qR) gene expression, HPV 16 E2 transfection and apoptosis regulation in human cervical squamous carcinoma cells (C33a and SiHa). METHODS: gC1qR expression was examined in C33a and SiHa cells using real-time PCR and Western blot analysis. Apoptosis of C33a and SiHa cells was assessed by flow cytometry. C33a and SiHa cell viability, migration and proliferation were detected using the water-soluble tetrazolium salt (WST-1) assay, a transwell assay and 3H-thymidine incorporation into DNA (3H-TdR), respectively. RESULTS: C33a and SiHa cells that were transfected with a vector encoding HPV 16 E2 displayed significantly increased gC1qR gene expression and p38 mitogen-activated protein kinase (p38 MAPK)/c-jun N-terminal kinase (JNK) activation as well as up-regulation of cellular apoptosis, which was abrogated by the addition of gC1qR small interfering RNA (siRNA). Furthermore, the changes in C33a and SiHa cell viability, migration and proliferation that were observed upon HPV 16 E2 transfection were abrogated by SB203580 (a p38 MAPK inhibitor) or SP600125 (a JNK inhibitor) treatment. CONCLUSION: These data support a mechanism whereby HPV 16 E2 induces apoptosis by silencing the gC1qR gene or inhibiting p38 MAPK/JNK signalling in cervical squamous cell carcinoma.


Subject(s)
Apoptosis , Carcinoma, Squamous Cell/pathology , DNA-Binding Proteins/metabolism , Membrane Glycoproteins/metabolism , Oncogene Proteins, Viral/metabolism , Receptors, Complement/metabolism , Signal Transduction , Uterine Cervical Neoplasms/pathology , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Survival , Female , Gene Expression Regulation, Neoplastic , Human papillomavirus 16 , Humans , MAP Kinase Kinase 4/metabolism , Protein Structure, Tertiary , Uterine Cervical Neoplasms/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
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