Molecular Mechanism of miR-29b on Gestational Diabetes and Its Influence on Trophoblast Cell Function

To explore the mechanism of miR-29b in gestational diabetes mellitus (GDM) and its effect on the function of trophoblast cell (TBC), the placenta tissues of 55 normal term pregnancies and 55 GDM patients were selected and rolled into control group and observation group. In the early stage, microRNA (miRNA) chips were utilized to screen the differentially expressed miRNAs in the placenta of observation group and control group. According to the microarray results of miRNAs, three differentially expressed miRNAs, namely let-7b, miR-1202, and miR-29b were selected. Then, the differences in the miR-29b level in the four groups were analyzed, namely the microRNA-29b (miR-29b minic), mini-control (minic control), microRNA-29b inhibitor (miR-29b inhibitor), and inhibitor control (inhibitor control). The results showed that miR-29b level in the placenta of observation group was substantially inferior to that of controls, with remarkable differences (P < 0.05). miR-29b level in miR-29b minic and minic control had significant changes (P < 0.01). The TBC activity of minic control was greatly superior to that of minic control, and there was considerable difference between the two (P < 0.05). The difference between miR-29b inhibitor and inhibitor control in TBC was not obvious, without considerable differences (P > 0.05). The invasion ability of miR-29b inhibitor TBC was notably superior to inhibitor control, and there were substantial differences (P < 0.05). To sum up, miR-29b had a significant inhibitory effect on the proliferation and cell activity of TBC, and can promote the apoptosis and death of TBC. Moreover, its inhibitory effect on cell migration and invasion was also suggested.

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MicroRNA expression profiling involved in Borax-induced anti-tumor effect using gene-chip analysis

10.21203/rs.2.20621/v1 ◽

2020 ◽

Author(s):

Lun Wu ◽

Ying Wei ◽

Wen-Bo Zhou ◽

Jiao Zhou ◽

Li-Hua Yang ◽

...

Keyword(s):

Signaling Pathway ◽

Hepg2 Cells ◽

Enrichment Analysis ◽

Gene Chip ◽

Differentially Expressed ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Ras Signaling ◽

Therapeutic Benefits ◽

Differentially Expressed Mirnas

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.

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P-117 Pre-selected for an award: Bioinformatic analysis of NRF2 in the study of association of NRF2 variant and male infertility related to smoking status

Human Reproduction ◽

10.1093/humrep/deab127.044 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

D Aydos ◽

O S Aydos ◽

Y Yukselten ◽

A Sunguroglu ◽

K Aydos

Keyword(s):

Dna Damage ◽

Male Infertility ◽

Mirna Expression ◽

Smoking Status ◽

Differentially Expressed ◽

Control Group ◽

Functional Variants ◽

Significant Difference ◽

Differentially Expressed Mirnas

Abstract Study question Could Nrf2 polymorphism (-617C>A; rs6721961) and oxidative stress (OS)-induced changes of signature seminal plasma (SP) miRNAs related to Nrf2 provide possible biomarkers of male infertility? Summary answer -617C>A SNP is associated with infertility through sperm OS DNA damage and miR-582-5p and miR-20a-5p, differentially represented between spermatozoa of smokers-non-smokers, might regulate Nrf2/ARE axis. What is known already As an extrinsic factor causing OS, smoking decreases male infertility by causing sperm membrane damage and DNA fragmentation. Expression of proteins related to the antioxidant defense system and phase 2 detoxifying enzymes controlled mainly by Nrf2/ARE pathway components is vital in managing OS-induced DNA damage. miRNAs, which multiple of are produced abundantly in male germ cells throughout spermatogenesis, have been detected in SP and contribute to multiple biological processes related to male reproductive events. miRNA-expression alterations may be induced in response to OS and without involving DNA sequence changes, miRNAs can provide additional mechanism of regulating the Nrf2 gene expression. Study design, size, duration Wild-type (WT) and SNP (-617) alleles in the Nrf2 gene were studied in 100 infertile cases and 100 controls and their associations with seminal parameters in relation to smoking status were assessed. In infertile cases, sperm DNA damage level was determined and compared among Nrf2 genotypes. Interactions between differentially expressed miRNAs (DEMIs) in response to smoking and Nrf2/ARE pathway components were visualized on a miRNA-mRNA regulatory network using CluePedia (v1.5.7) plugin of Cytoscape software (v3.8.2). Participants/materials, setting, methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to genotype the Nrf2 SNP (-617). DNA damages were analyzed by Comet assay. DEMIs were identified by a comprehensive bioinformatics analysis using the miRNA expression dataset GSE44134 downloaded from the GEO database. Predicted targets of DEMIs in smokers were identified by mirDIP portal. Known interactions between Nrf2 and its first neighbors were visualized after selecting STRING-actions, miRTarBase and miRecords validated miRNA source files from CluePedia panel. Main results and the role of chance There was significant difference for Nrf2 polymorphism between fertile and infertile males. The A allele was detected more frequently in the patient group; (P = 0.001). The frequencies of the C and A alleles of the Nrf2 were 62% and 38% in patients, and 78% and 44% in control group. The AA genotype was higher in the infertiles; 14% vs. 3% (P = 0.001). In smokers, sperm quality decreased significantly in AA genotype. The risk of DNA damage was highest with 224.58 AU in the AA genotype group, whereas it is the lowest with 164.56 AU in those carrying the CC genotype (P < 0.005). 21 differentially expressed miRNAs (including 7 downregulated and 14 upregulated in smokers) were identified. Among the upregulated DEMIs, miR-582-5p, miR-20a-5p, miR-573, miR-186-5p, miR-499a-5p were found to target the Nrf2 mRNA, suggesting their usage as biomarkers capable of indicating the antioxidant ability of the male reproductive system. The interrelations between Nrf2/Nrf2 direct interactors and DEMIs revealed the regulatory role of hsa-miR-20a-5p in SQSTM1/p62-Keap1-Nrf2 axis linked to selective autophagy. hsa-miR-582-5p was found to regulate the JNK/Jun/caspase-3 pathway, previously shown to be activated in response to OS, in which JUN can activate or suppress the Nrf2 expression. Limitations, reasons for caution Small number of cases while evaluating the effect of smoking weakens our ability to generalize the results. Including other coexisting factors and larger patient groups carrying other functional variants of Nrf2 as well as confirming the results at the protein level would further strengthen the results of the study. Wider implications of the findings This study is the first to report -617C>A polymorphism in the Nrf2 gene in the Turkish population and such a SNP may cause impaired fertility in men, especially in smokers, through oxidative metabolism. Considering these data may be valuable in determining risk groups. Trial registration number N/A

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New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302011000800003 ◽

2011 ◽

Vol 55 (8) ◽

pp. 512-519 ◽

Cited By ~ 12

Author(s):

Romina P. Grinspon ◽

Rodolfo A. Rey

Keyword(s):

Sertoli Cell ◽

Cell Function ◽

Cell Activity ◽

Tanner Stage ◽

Inhibitory Effect ◽

Male Hypogonadism ◽

Fetal Life ◽

Infancy And Childhood ◽

Stimulation Tests ◽

Enzyme Defects

Sertoli cells are the most active cell population in the testis during infancy and childhood. In these periods of life, hypogonadism can only be evidenced without stimulation tests, if Sertoli cell function is assessed. AMH is a useful marker of prepubertal Sertoli cell activity and number. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Serum AMH is undetectable in anorchidic patients. In primary or central hypogonadism affecting the whole gonad and established in fetal life or childhood, serum AMH is low. Conversely, when hypogonadism affects only Leydig cells (e.g. LHβ mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.

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Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

Stem Cells International ◽

10.1155/2016/9156731 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Yajing Huang ◽

Yanming Wu ◽

Xinwen Chang ◽

Yan Li ◽

Kai Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Cell Function ◽

Trophoblast Cell ◽

Migration And Invasion ◽

Human Umbilical Cord ◽

Trophoblast Cells ◽

Human Trophoblast ◽

Cell Functions

Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs) are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

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Underexpression of 4 Placenta-Associated MicroRNAs in Complete Hydatidiform Moles

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182574439 ◽

2012 ◽

Vol 22 (6) ◽

pp. 1075-1080 ◽

Cited By ~ 12

Author(s):

Quan Na ◽

Dan Wang ◽

Weiwei Song

Keyword(s):

In Situ Hybridization ◽

Hydatidiform Mole ◽

Polymerase Chain Reaction Analysis ◽

Normal Pregnancy ◽

Differentially Expressed ◽

Control Group ◽

Differentially Expressed Mirnas ◽

Hydatidiform Moles

ObjectiveSeveral placental microRNAs (miRNAs) have been identified as placenta-associated miRNAs with the potential of estimating the condition of the placenta. However, our understanding of these miRNAs is limited. The aim of this study was to determine the expression of 8 placenta-associated miRNAs (miR-512-3p, miR-517a, miR-517b, miR-518b, miR-519a, miR-1185, miR-1283, and miR-1323) in complete hydatidiform mole (CHM).MethodsSamples were obtained from patients with CHM (CHM group, n = 12) and elective terminations of normal pregnancy (control group, n = 20). We detected differentially expressed placenta-associated miRNAs in placenta by quantitative real-time reverse transcriptase–polymerase chain reaction analysis. Subsequently, we assessed the expression location of differentially expressed miRNAs by in situ hybridization analysis.ResultsFour placenta-associated miRNAs (miR-517a, miR-517b, miR-518b, and miR-519a) were underexpressed in the CHM group, compared with the control group (P < 0.01). When further investigating these 4 miRNAs with regard to in vivo localization by in situ hybridization, we found that 2 miRNAs (miR-517b and miR-518b) were detected exclusively in the trophoblast layer, with little signal (if any) observed in villous stroma cells.ConclusionsThe results show that 4 miRNAs (miR-517a, miR-517b, miR-518b, and miR-519a) are deregulated in CHM, which suggests the involvement of these miRNAs in the functions of CHM placenta.

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miR-132 serves as a diagnostic biomarker in gestational diabetes mellitus and its regulatory effect on trophoblast cell viability

Diagnostic Pathology ◽

10.1186/s13000-019-0899-9 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Xuegui Zhou ◽

Cuiping Xiang ◽

Xiaoxia Zheng

Keyword(s):

Diabetes Mellitus ◽

Cell Proliferation ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Cell Function ◽

Fasting Blood Glucose ◽

Trophoblast Cell ◽

Operating Characteristics ◽

Diagnostic Potential

Abstract Background Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes. Strategies that improve trophoblast cell function are important methods for GDM treatment. This study aimed to investigate the expression and diagnostic potential of microRNA-132 (miR-132) in GDM patients, and further analyzed the effects of miR-132 on HTR-8/SVneo cell proliferation. Methods Quantitative real-time PCR was applied to estimate the expression of miR-132. A receiver operating characteristics curve (ROC) analysis was performed to evaluate the diagnostic value of serum miR-132 in GDM patients. In vitro regulation of miR-132 in trophoblast cell HTR-8/SVneo was achieved by cell transfection, and the effects of miR-132 on cell proliferation were assessed using CCK-8 assay. Results Expression of miR-132 was decreased in serum and placenta tissues in GDM patients compared with the healthy women. A negative correlation was found between the serum miR-132 levels and fasting blood glucose of the GDM patients. A ROC curve shown the serum miR-132 had considerable diagnostic accuracy with an area under the curve (AUC) of 0.898. High glucose (HG) treatment induced an inhibition in HTR-8/SVneo cell proliferation and the expression of miR-132. The overexpression of miR-132 in HTR-8/SVneo cells could markedly rescued the HG - induced suppressed cell proliferation. Conclusion All the data of this study revealed the reduced expression of miR-132 in serum and placenta tissues of GDM, and serum miR-132 serves a candidate biomarker in the diagnosis of GDM. miR-132 may act a protective role against GDM via enhancing the trophoblast cell proliferation.

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Identification and characterization of heat-responsive microRNAs at the booting stage in two rice varieties 9311 and Nagina 22

Genome ◽

10.1139/gen-2020-0175 ◽

2021 ◽

Author(s):

Ying Luo ◽

Tao Wang ◽

Dan Yang ◽

Biao Luo ◽

Weiping Wang ◽

...

Keyword(s):

Stress Responses ◽

High Throughput Sequencing ◽

Target Genes ◽

Elevated Temperatures ◽

Differentially Expressed ◽

Control Group ◽

Microrna Target ◽

Rice Varieties ◽

Booting Stage ◽

Differentially Expressed Mirnas

Abstract: MicroRNAs (miRNAs) are small, non-coding, regulatory RNAs that play important roles in abiotic stress responses in plants. but their regulatory roles in the adaptive response to heat stress at the booting stage in two rice varieties 9311 and Nagina 22, remain largely unknown. In this study, 464 known miRNAs and 123 potential novel miRNAs were identified. Of these miRNAs, a total of 90 differential expressed miRNAs were obtained with 9311 libraries as control group, of which 54 upregulated and 36 downregulated miRNAs. To gain insight into functional significance, 2773 potential target genes of these 90 differentially expressed miRNAs were predicted. GO enrichment showed that the predicted target genes of differentially expressed miRNAs including NACs, LACs, CSD, and Hsp40. KEGG pathway analysis showed that target genes of these differentially expressed miRNAs were significantly enriched in plant hormone signal transduction pathway. The expression levels of ten differentially expressed miRNAs and their target genes obtained by qRT-PCR were largely consistent with the sequencing results. This study lays a foundation for the elucidation of the miRNA-mediated regulatory mechanism in rice at elevated temperatures. Key words: rice, heat-responsive, microRNA, target gene, booting stage, high-throughput sequencing

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PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression

BioMed Research International ◽

10.1155/2022/3697944 ◽

2022 ◽

Vol 2022 ◽

pp. 1-11

Author(s):

Wittaya Chaiwangyen ◽

Komsak Pintha ◽

Payungsak Tantipaiboonwong ◽

Piyawan Nuntaboon ◽

Orawan Khantamat ◽

...

Keyword(s):

Mirna Expression ◽

Cell Function ◽

Premature Mortality ◽

Trophoblast Cell ◽

Migration And Invasion ◽

Trophoblast Cells ◽

High Concentration ◽

Particulate Pollution ◽

Cell Functions ◽

Pollution Exposure

Air pollution is one of the largest global environmental health hazards that threaten premature mortality or morbidity. Particulate matter 10 (PM10) has been demonstrated to contribute to several human diseases via dysregulated miRNA expression. Trophoblast cells play a key role in implantation and placentation for a successful pregnancy. Nonetheless, the PM10 associated trophoblast cell functions during pregnancy and miRNA expression are still unknown. Our study showed that PM10 affected HTR-8/SVneo cell viability and also decreased cell proliferation, migration, and invasion. A high concentration of PM10 caused an increase in HTR-8/SVneo cell apoptosis. Treatment with PM10 induced inflammation through the upregulated IL-1β, IL-6, and TNF-α expression in trophoblast cells. In PM10-treated HTR-8/SVneo cells, miR-125b-5p expression was considerably increased and TXNRD1 was found to be negatively related to miR-125b-5p. Collectively, our findings revealed that PM10 could alter miR-125b-5p expression by targeting TXNRD1 and suppressing trophoblast cell functions. Additional investigations relating to the function of miR-125b-5p and its target on particulate pollution exposure in trophoblast are warranted for future biomarker or effective therapeutic approaches.

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Dysregulation of autophagy-associated microRNAs in condyloma acuminatum

10.21203/rs.3.rs-15974/v1 ◽

2020 ◽

Author(s):

Shi Wu ◽

Dan Lu ◽

Xinkai Zheng ◽

Jin Xu ◽

Zhen Li ◽

...

Keyword(s):

Cell Proliferation ◽

Light Chain ◽

Target Genes ◽

Condyloma Acuminatum ◽

Differentially Expressed ◽

Control Group ◽

Healthy Controls ◽

Related Protein ◽

Ki 67 ◽

Differentially Expressed Mirnas

Abstract Objectives This study was designed to investigate the miRNAs that regulate the cell proliferation of condyloma acuminatum (CA) lesions and their targets.Methods The expression of Ki-67 in 26 CA patients compared with 10 healthy controls was assessed by immunohistochemistry. And the different miRNAs in 4 CA patients and 4 control cases were analyzed by bioinformatics. PCR was used to validate the expression of screened miRNA and its corresponding target genes.Results The expression of Ki-67 was abnormally increased in CA compared with healthy controls ( P <0.05). The comparison of the control group with the CA group revealed 81 differentially expressed miRNAs, of which 56 were downregulated and 25 were upregulated. Two of the differentially expressed miRNAs, miR-30a-5p and miR-514a-3p, are associated with cell proliferation and their target genes are autophagy-related protein (Atg) 5 and Atg12, and Atg3 and Atg12, respectively. PCR results showed that the expression levels of miR-30a-5p and miR-514a-3p were decreased in CA patients compared with healthy controls ( P <0.05), whereas the expression of Atg5, Atg12 and Atg3 was increased ( P <0.05). The expression of the autophagy proteins microtubule-associated protein 1 light chain 3 (LC3) and P62/SQSTM1 (P62) was abnormally increased in the local lesion tissue of the 26 patients with CA compared with the 10 healthy controls, as assessed by immunohistochemistry ( P <0.05).Conclusions Our results suggest that autophagy levels may be modulated by has-miRNA30a-5p and has-miRNA514a-3p in CA patients, leading to dysregulated cell proliferation.

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Inhibition of miR-141 and miR-200a Increase DLC-1 and ZEB2 Expression, Enhance Migration and Invasion in Metastatic Serous Ovarian Cancer

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17082766 ◽

2020 ◽

Vol 17 (8) ◽

pp. 2766 ◽

Cited By ~ 2

Author(s):

Norhazlina Abdul Wahab ◽

Zahreena Othman ◽

Noor Wahidah Mohd Nasri ◽

Mohd Helmy Mokhtar ◽

Siti Fatimah Ibrahim ◽

...

Keyword(s):

Ovarian Cancer ◽

Differentially Expressed ◽

Locked Nucleic Acid ◽

Migration And Invasion ◽

Serous Ovarian Cancer ◽

Novel Mirna ◽

Ovarian Carcinogenesis ◽

Differentially Expressed Mirnas

The role of microRNA (miRNA) in ovarian cancer has been extensively studied as a regulator for its targeted genes. However, its specific role in metastatic serous ovarian cancer (SOC) is yet to be explored. This paper aims to investigate the differentially expressed miRNAs in metastatic SOC compared to normal. Locked nucleic acid PCR was performed to profile miRNA expression in 11 snap frozen metastatic SOC and 13 normal ovarian tissues. Functional analysis and regulation of their targeted genes were assessed in vitro. Forty-eight miRNAs were significantly differentially expressed in metastatic SOC as compared to normal. MiR-19a is a novel miRNA to be upregulated in metastatic SOC compared to normal. DLC1 is possibly regulated by miR-141 in SOC. MiR-141 inhibition led to significantly reduced cell viability. Cell migration and invasion were significantly increased following miRNA inhibition. This study showed the aberrantly expressed miRNAs in metastatic SOC and the roles of miRNAs in the regulation of their targeted genes and ovarian carcinogenesis.

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