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1.
Mol Nutr Food Res ; : e2300871, 2024 May 05.
Article En | MEDLINE | ID: mdl-38704749

SCOPE: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS. CONCLUSION: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.

2.
Front Pediatr ; 12: 1327742, 2024.
Article En | MEDLINE | ID: mdl-38562133

Neuronopathy, distal hereditary motor, type VIII is an exceedingly rare autosomal dominant genetic disorder, also known as congenital non-progressive distal spinal muscular atrophy. It is characterized by progressive weakness in distal motor function and atrophy of muscles, without accompanying sensory impairment. Presently, there is limited literature on this condition, and accurate epidemiological data regarding its incidence remains unavailable. We report a paediatric case of distal hereditary motor, type VIII that is caused by a heterozygous missense mutation in the TRPV4 gene (NM_021625): c.805C>T. The proband is a 7-year-old male child. During pregnancy, his mother had prenatal ultrasound revealing "inward turning of the feet", a condition persisting after birth. The proband is currently unable to stand independently, exhibiting bilateral clubfoot deformity. Although possessing normal cognitive function, he cannot walk unaided. Computed radiography findings reveal pelvic tilt, bilateral knee joint valgus, and bilateral clubfoot. The patient underwent familial exome sequencing, revealing a mutation in the TRPV4 gene (NM_021625): c.805C>T (p.Arg269Cys). Considering the patient's medical history, clinical manifestations, imaging studies, and genetic test results, the diagnosis for this individual is Neuronopathy, distal hereditary motor, type VIII. This report documents a case involving the TRPV4 gene mutation associated with Neuronopathy, distal hereditary motor, type VIII, contributing valuable case reference for the early diagnosis of this condition.

3.
Psychiatry Clin Neurosci ; 77(12): 631-637, 2023 Dec.
Article En | MEDLINE | ID: mdl-37632723

BACKGROUND: Antepartum depression is a prevalent unhealthy mental health problem worldwide, particularly in low-income countries. It is a major contributor to adverse birth outcomes. Previous studies linking antepartum depression to birthweight have yielded conflicting results, which may be the reason that the depressive symptoms were only measured once during pregnancy. This study aimed to explore the associations between trajectories of antepartum depressive symptoms and birthweight. METHODS: Depressive symptoms were assessed prospectively at each trimester in 3699 pregnant women from 24 hospitals across 15 provinces in China, using the Edinburgh Postpartum Depression Scale (EPDS). Higher scores of EPDS indicated higher levels of depressive symptoms. Associations between trajectories of depressive symptoms and birthweight were examined using group-based trajectory modeling (GBTM), propensity score-based inverse probability of treatment weighting (IPTW), and logistic regression. RESULTS: GBTM identified five trajectories. Compared with the low-stable trajectory of depressive symptoms, only high-stable (OR = 1.35, 95% CI: 1.15-2.52) and moderate-rising (OR = 1.18, 95% CI: 1.12-1.85) had an increased risk of low birthweight (LBW) in the adjusted longitudinal analysis of IPTW. There was no significant increase in the risk of LBW in moderate-stable and high-falling trajectories. However, trajectories of depressive symptoms were not associated with the risk of macrosomia. CONCLUSION: Antepartum depressive symptoms were not constant. Trajectories of depressive symptoms were associated with the risk of LBW. It is important to optimize and implement screening, tracking, and intervention protocols for antepartum depression, especially for high-risk pregnant women, to prevent LBW.


Depression, Postpartum , Pregnancy Complications , Female , Pregnancy , Humans , Depression/epidemiology , Depression/diagnosis , Birth Weight , Prospective Studies , Pregnant Women/psychology , Pregnancy Complications/psychology , Depression, Postpartum/diagnosis , Risk Factors
4.
Psychiatry Res ; 326: 115284, 2023 08.
Article En | MEDLINE | ID: mdl-37302355

Previous studies only assessed the association between depressive symptoms and risk of preterm birth (PTB) at a time-point during pregnancy, resulting in inconsistent or contradictory results. Therefore, we aimed to explore the associations between the trajectories of depressive symptoms during pregnancy and risk of PTB. In total, 7732 pregnant women were included in 24 hospitals from 15 provinces of China. The Edinburgh Postpartum Depression Scale (EPDS) was used to evaluate depressive symptoms in the first, second, and third trimesters. Associations between depressive symptoms and risk of PTB were performed by group-based trajectory modeling (GBTM), propensity score-based inverse probability of treatment weighting (IPTW), and logistic regression. GBTM identified five trajectories: compared with persistently low-stable trajectory of depressive symptoms, women with moderate-stable (OR = 1.23, 95% CI: 1.02-1.76), high-falling (OR = 1.35, 95% CI: 1.11-2.21), moderate-rising (OR = 1.38, 95% CI: 1.06-2.04), and high-stable trajectory of depressive symptoms (OR = 1.40, 95% CI: 1.16-3.28) had an increased risk of PTB. In addition, the associations between trajectories of depressive symptoms and risk of PTB were most significant in multiparous women with a history of PTB. There was no difference in the risk of early-moderate PTB among different trajectories of depressive symptoms and only the risk of late PTB was different among different trajectories. In conclusion, the depressive symptoms of pregnant women were not constant during pregnancy, and different trajectories of depressive symptoms were associated with different risks of PTB.


Pregnancy Complications , Premature Birth , Female , Pregnancy , Infant, Newborn , Humans , Depression/complications , Depression/epidemiology , Depression/diagnosis , Premature Birth/epidemiology , Prospective Studies , Risk Factors , Pregnancy Complications/epidemiology , Pregnancy Complications/diagnosis , Parity
5.
Diabetes Res Clin Pract ; 198: 110619, 2023 Apr.
Article En | MEDLINE | ID: mdl-36906233

AIMS: We explored the complex relationships between pre-pregnancy body mass index (pBMI) and maternal or infant complications and the mediating role of gestational diabetes mellitus (GDM) in these relationships. METHODS: Pregnant women from 24 hospitals in 15 different provinces of China were enrolled in 2017 and followed through 2018. Propensity score-based inverse probability of treatment weighting, logistic regression, restricted cubic spline models, and causal mediation analysis were utilized. In addition, the E-value method was used to evaluate unmeasured confounding factors. RESULTS: A total of 6174 pregnant women were finally included. Compared to women with a normal pBMI, obese women had a higher risk for gestational hypertension (odds ratio [OR] = 5.38, 95% confidence interval [CI]: 3.48-8.34), macrosomia (OR = 2.65, 95% CI: 1.83-3.84), and large for gestational age (OR = 2.05, 95% CI: 1.45-2.88); 4.73% (95% CI: 0.57%-8.88%), 4.61% (95% CI: 0.51%-9.74%), and 5.02% (95% CI: 0.13%-10.18%) of the associations, respectively, were mediated by GDM. Underweight women had a high risk for low birth weight (OR = 1.42, 95% CI: 1.15-2.08) and small for gestational age (OR = 1.62, 95% CI: 1.23-2.11). Dose-response analyses indicated that 21.0 kg/m2 may be the appropriate tipping point pBMI for risk for maternal or infant complications in Chinese women. CONCLUSION: A high or low pBMI is associated with the risk for maternal or infant complications and partly mediated by GDM. A lower pBMI cutoff of 21 kg/m2 may be appropriate for risk for maternal or infant complications in pregnant Chinese women.


Diabetes, Gestational , Female , Pregnancy , Infant , Humans , Diabetes, Gestational/epidemiology , Diabetes, Gestational/therapy , Longitudinal Studies , Body Mass Index , Cohort Studies , China/epidemiology
7.
Acta Histochem ; 125(1): 151991, 2023 Jan.
Article En | MEDLINE | ID: mdl-36563468

Placenta accreta is an abnormality of the placenta caused by the chorionic villi invading the muscular layer, which can cause serious bleeding, infection, shock, bladder invasion, uterine perforation, and even death. However, the etiology of placental accreta is not entirely clear. In the present study, high-throughput sequencing results showed that FYN is highly expressed in the placental accreta position in the placenta accreta group and is a key regulator of cell invasion and migration. Therefore, we aimed to evaluate the role and potential molecular mechanism of FYN in placenta accreta. The results showed that FYN was highly expressed in the placenta tissues of the placenta accreta group. Furthermore, the levels of phosphorylated STAT3, p38, and JNK in the placenta accreta group were remarkably increased compared with those in the control group. In addition, FYN knockdown considerably decreased the migration and invasion rates of trophoblast cells (HTR8/SVneo) and inhibited the levels of phosphorylated STAT3, p38, and JNK. After subsequently blocking these signaling pathways, the invasion and migration abilities of HTR8/SVneo cells were substantially decreased. In conclusion, FYN may promote excessive trophocyte cell invasion by activating STAT3, p38, and JNK pathways and can be a new target for placenta accreta prevention and treatment.


Placenta Accreta , Placenta , Female , Humans , Pregnancy , Cell Movement , Chorionic Villi/metabolism , MAP Kinase Signaling System , Placenta/metabolism , Placenta Accreta/metabolism , STAT3 Transcription Factor/metabolism , Trophoblasts/metabolism
9.
Clin Exp Hypertens ; 44(4): 334-340, 2022 May 19.
Article En | MEDLINE | ID: mdl-35343343

BACKGROUND: At present, pre-eclampsia is a growing concern and still a diagnostic challenge for obstetricians. AIMS: This study aimed to evaluate whether the relationship of second trimester of pregnancy neutrophil count differed among pregnancies with mild preeclampsia, severe preeclampsia, and healthy status and explore whether or not neutrophil count in the second trimester of pregnancy would be useful as new predictors of subsequent preeclampsia. PATIENTS AND METHODS: This study involved 933 pregnancies from 1 January 2018 to 30 January 2021, comprising 396 healthy pregnancies, 222 pregnancies with mild preeclampsia, and 315 pregnancies with severe preeclampsia. The relationship between preeclampsia and neutrophil count was analyzed by multiple logistic regression. In addition, maternal placental tissues of three groups were immunohistochemically stained for myeloperoxidase (MPO). RESULTS: Neutrophil count was significantly higher in pregnancies with preeclampsia (including pregnancies with mild and severe preeclampsia) than that in healthy pregnancies. The neutrophil count level was prominently higher in patients with severe preeclampsia compared with those with mild preeclampsia (p < .001). The neutrophil count level was significantly positively associated with preeclampsia after adjusting for gestational week at time of blood sampling, BMI, and age (ß:1.23; 95%CI:1.09-1.36; p < .0001). In addition, MPO expressions of placental tissues in preeclamptic groups were significantly increased than these in healthy pregnant controls (p < .05). CONCLUSIONS: Increased neutrophil count in the second trimester of pregnancy was significantly positively associated with preeclampsia. Hence, neutrophil count plays a role in predicting the severity of preeclampsia. At the same time, it may be an independent predictor of subsequent preeclampsia.Abbreviations: BMI: body mass index; MPO: myeloperoxidase.


Pre-Eclampsia , Pregnancy , Humans , Female , Pre-Eclampsia/diagnosis , Peroxidase , Placenta , Pregnancy Trimester, Second , Case-Control Studies
10.
Int J Gen Med ; 14: 3049-3057, 2021.
Article En | MEDLINE | ID: mdl-34234533

BACKGROUND: The midpregnancy normal-range HbA1c value and adverse birth outcomes were controversial. To address this lack of data, we examined the associations between midpregnancy normal-range HbA1c value and adverse birth outcomes. OBJECTIVE: To evaluate whether an association exists between the midpregnancy normal-range HbA1c value and adverse birth outcomes. MATERIALS AND METHODS: A total of 8389 women in their midpregnancy with normal gestational HbA1c value from the Affiliated Hospital of Jining Medical University in China participated in this study from January to December 2019. Subjects were stratified on the basis of their midpregnancy HbA1c value, and multivariate logistic regression was implemented to investigate the association between different HbA1c values and adverse birth outcomes. RESULTS: Incidence of preterm birth, macrosomia, and large for gestational age (LGA) for 8389 subjects were 4.8%, 6.3% and 16.5%, respectively. The multivariate logistic regression model demonstrated that the risk of preterm birth (adjusted odds ratio [OR]: 1.71 and 95% confidence interval [CI]: 1.25-2.34), macrosomia (OR: 1.68 and 95% CI: 1.26-2.22), and LGA (OR: 1.53 and 95% CI: 1.28-1.83) increase for every increase of 1% maternal HbA1c. Women with a prepregnancy body mass index (BMI) of < 25 kg/m2 have a stronger correlation with HbA1c values and adverse birth outcomes than women with a prepregnancy BMI of ≥25 kg/m2. CONCLUSION: Our results indicated that the midpregnancy normal-range HbA1c level within the normal range is associated with adverse birth outcomes. Monitoring and controlling HbA1c may reduce the risk of adverse birth outcomes.

11.
Mol Nutr Food Res ; 65(12): e2100072, 2021 06.
Article En | MEDLINE | ID: mdl-33938121

SCOPE: Maternal nutrition during pregnancy is related to intrauterine fetal development. The authors' previous work reports that prenatal high sucrose (HS) diet impaired micro-vascular functions in postnatal offspring. It is unclear whether/how prenatal HS causes vascular injury during fetal life. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Pregnant HS increases maternal weight before delivery. Fetal thoracic aorta is separated for experiments. Angiotensin II (AII)-stimulated vascular contraction of fetal thoracic arteries in HS group is greater, which mainly results from the enhanced AT1 receptor (AT1R) function and the downstream signaling. Nifedipine significantly increases vascular tension in HS group, indicating that the L-type calcium channels (LTCCs) function is strengthened. 2-Aminoethyl diphenylborinate (2-APB), inositol 1,4,5-trisphosphate receptors (IP3Rs) inhibitor, increases vascular tension induced by AII in HS group and ryanodine receptors-sensitive vascular tone shows no difference in the two groups, which suggested that the activity of IP3Rs-operated calcium channels is increased. CONCLUSION: These findings suggest that prenatal HS induces vascular dysfunction of thoracic arteries in fetal offspring by enhancing AT1R, LTCCs function and IP3Rs-associated calcium channels, providing new information regarding the impact of prenatal HS on the functional development of fetal vascular systems.


Dietary Sucrose/adverse effects , Endothelium, Vascular/drug effects , Thoracic Arteries/drug effects , Thoracic Arteries/embryology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Body Weight/drug effects , Endothelium, Vascular/embryology , Endothelium, Vascular/physiopathology , Female , Litter Size , Losartan/pharmacology , Male , Maternal Nutritional Physiological Phenomena , Nitric Oxide Synthase Type III/metabolism , Pregnancy , Prenatal Exposure Delayed Effects , Rats, Sprague-Dawley , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/metabolism , Thoracic Arteries/physiopathology
12.
BMJ Open ; 11(3): e044933, 2021 03 23.
Article En | MEDLINE | ID: mdl-33757952

PURPOSE: A multicentre prospective cohort study, known as the Chinese Pregnant Women Cohort Study (CPWCS), was established in 2017 to collect exposure data during pregnancy (except environmental exposure) and analyse the relationship between lifestyle during pregnancy and obstetric outcomes. Data about mothers and their children's life and health as well as children's laboratory testing will be collected during the offspring follow-up of CPWCS, which will enable us to further investigate the longitudinal relationship between exposure in different periods (during pregnancy and childhood) and children's development. PARTICIPANTS: 9193 pregnant women in 24 hospitals in China who were in their first trimester (5-13 weeks gestational age) from 25 July 2017 to 26 November 2018 were included in CPWCS by convenience sampling. Five hospitals in China which participated in CPWCS with good cooperation will be selected as the sample source for the Chinese Pregnant Women Cohort Study (Offspring Follow-up) (CPWCS-OF). FINDINGS TO DATE: Some factors affecting pregnancy outcomes and health problems during pregnancy have been discovered through data analysis. The details are discussed in the 'Findings to date' section. FUTURE PLANS: Infants and children and their mothers who meet the criteria will be enrolled in the study and will be followed up every 2 years. The longitudinal relationship between exposure (questionnaire data, physical examination and biospecimens, medical records, and objective environmental data collected through geographical information system and remote sensing technology) in different periods (during pregnancy and childhood) and children's health (such as sleeping problem, oral health, bowel health and allergy-related health problems) will be analysed. TRAIL REGISTRATION NUMBER: CPWCS was registered with ClinicalTrials.gov on 18 January 2018: NCT03403543. CPWCS-OF was registered with ClinicalTrials.gov on 24 June 2020: NCT04444791.


Pregnant Women , Child , China/epidemiology , Cohort Studies , Female , Follow-Up Studies , Humans , Infant , Pregnancy , Prospective Studies
13.
Arch Gynecol Obstet ; 303(3): 645-652, 2021 03.
Article En | MEDLINE | ID: mdl-33515274

PURPOSE: Our objective of this study was to investigate whether first trimester serum pregnancy-associated plasma protein-A (PAPP-A) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies by a retrospective cohort analysis. METHODS: A total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of BMI and age matched, healthy pregnant controls. PAPP-A multiples of the median (MoM) were acquired from laboratory data files in 1 January 2017-30 September 2019. The probable maternal serum biochemical predictor of placenta accreta was analyzed by using multiple logistic regression analysis. RESULTS: PAPP-A MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.009 < 0.05, p < 0.001). Serum PAPP-A was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, age, smoking, and previous cesarean section history (OR: 3.51; 95% CI: 1.77-6.94; p = 0.0003 < 0.05). In addition, smoking (OR: 9.17; 95% CI: 1.69-49.62; p = 0.010 < 0.05) and previous cesarean section history (OR: 2.75; 95% CI: 1.23-6.17; p = 0.014 < 0.05) were also significantly associated with placenta accreta. CONCLUSION: Increased first trimester serum PAPP-A was significantly positively associated with placenta accreta, suggesting that the potential role of PAPP-A in identifying pregnancies at high risk for placenta accreta. Smoking and previous cesarean section history may be the risk factors for accreta in placenta previa patients.


Placenta Accreta/blood , Placenta Previa/blood , Pregnancy Trimester, First/blood , Pregnancy-Associated Plasma Protein-A/analysis , Adult , Cesarean Section , Female , Gestational Age , Humans , Pregnancy , Pregnancy-Associated Plasma Protein-A/metabolism , Retrospective Studies , Risk Factors
14.
Biol Reprod ; 103(6): 1229-1237, 2020 12 01.
Article En | MEDLINE | ID: mdl-32902654

Human placental vessels (HPVs) play important roles in the exchange of metabolites and oxygen in maternal-fetal circulation. Endothelial-derived prostacyclin (prostaglandin I2, PGI2) is a critical endothelial vasodilator in the body. However, the physiological and pharmacological functions of endothelial PGI2 in the human placenta are still unclear. Human, sheep, and rat blood vessels were used in this study. Unlike non-placental vessels (non-PVs), the PGI2 synthesis inhibitor tranylcypromine (TCP) did not modify 5-hydroxytryptamine (5-HT)-induced vascular contraction, indicating that endothelial-derived PGI2 was weak in PVs. Vascular responses to exogenous PGI2 showed slight relaxation followed by a significant contraction at a higher concentration in HPV, which was inhibited by the thromboxane-prostanoid (TP) receptors antagonist SQ-29,548. Testing PVs and non-PVs from sheep also showed similar functional results. More TP receptors than PGI2 (IP) receptors were observed in HPVs. The whole-cell K+ current density of HPVs was significantly weaker than that of non-PVs. This study demonstrated the specific characteristics of the placental endogenous endothelial PGI2 system and the patterns of placental vascular physiological/pharmacological response to exogenous PGI2, showing that placental endothelial PGI2 does not markedly contribute to vascular dilation in the human placenta, in notable contrast to non-PVs. The results provide crucial information for understanding the endothelial roles of HPVs, which may be helpful for further investigations of potential targets in the treatment of diseases such as preeclampsia.


Endothelium, Vascular/drug effects , Epoprostenol/pharmacology , Placenta/blood supply , Vasodilation/drug effects , 6-Ketoprostaglandin F1 alpha/genetics , 6-Ketoprostaglandin F1 alpha/metabolism , Animals , Cells, Cultured , Electrophysiological Phenomena , Female , Gene Expression Regulation/drug effects , Humans , Patch-Clamp Techniques , Phenylephrine/pharmacology , Potassium Channels , Pregnancy , Rats , Serotonin/pharmacology , Sheep
15.
Placenta ; 101: 39-44, 2020 11.
Article En | MEDLINE | ID: mdl-32916477

OBJECTIVES: In this retrospective study, we investigated whether first trimester serum placental growth factor (PIGF) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies. METHODS: In 1 January 2017-30 September 2019, a total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of age and BMI-matched, healthy pregnant controls. PIGF multiples of the median (MoM) were acquired from laboratory data files. The predictor of placenta accreta was analyzed by using multiple logistic regression analysis. RESULTS: PIGF MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.0098 < 0.01, p = 0.0002 < 0.01). Serum PIGF was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, and age (OR: 4.83; 95% CI: 1.91-12.24;p = 0.0009 < 0.01). In addition, previous cesarean section history (OR: 2.75; 95% CI: 1.23-6.17; p = 0.014 < 0.05) and smoking (OR: 9.17; 95% CI: 1.69-49.62; p = 0.010 < 0.05) were also significantly associated with placenta accreta. CONCLUSION: Increased first trimester serum PIGF was significantly positively associated with placenta accreta, suggesting that the potential role of PIGF in identifying pregnancies at high risk for placenta accreta. Previous cesarean section history and smoking may be the risk factors for accreta in placenta previa patients.


Placenta Accreta/blood , Placenta Growth Factor/blood , Pregnancy Trimester, First/blood , Adult , Biomarkers/blood , Female , Humans , Placenta/metabolism , Pregnancy , Retrospective Studies
17.
Biomed Res Int ; 2018: 6242173, 2018.
Article En | MEDLINE | ID: mdl-30018982

High-risk HPV is clearly associated with cervical cancer. HPV integration has been confirmed to promote carcinogenesis in the previous studies. In our study, a total of 285 DNA breakpoints and 287 RNA breakpoints were collected. We analyzed the characteristic of HPV integration in the DNA and RNA samples. The results revealed that the patterns of HPV integration in RNA and DNA samples differ significantly. FHIT, KLF5, and LINC00392 were the hotspot genes integrated by HPV in the DNA samples. RAD51B, CASC8, CASC21, ERBB2, TP63, TEX41, RAP2B, and MYC were the hotspot genes integrated by HPV in RNA samples. Breakpoints of DNA samples were significantly prone to the region of INTRON (P < 0.01, Chi-squared test), whereas in the RNA samples, the breakpoints were prone to EXON. Pathway analysis had revealed that the breakpoints of RNA samples were enriched in the pathways of transcriptional misregulation in cancer, cancer pathway, and pathway of adherens junction. Breakpoints of DNA samples were enriched in the pathway of cholinergic synapse. In summary, our data helped to gain insights into the HPV integration sites in DNA and RNA samples of cervical cancer. It had provided theoretical basis for understanding the mechanism of tumorigenesis from the perspective of HPV integration in the HPV-associated cervical cancers.


DNA, Viral , Neoplasm Proteins/genetics , Papillomaviridae/genetics , Papillomavirus Infections/genetics , Transcriptome , Uterine Cervical Neoplasms/virology , Female , Genome, Human , Humans , RNA, Long Noncoding , Virus Integration , rap GTP-Binding Proteins
18.
Oncol Lett ; 11(4): 2475-2480, 2016 Apr.
Article En | MEDLINE | ID: mdl-27073501

The present study aimed to evaluate the effects of lysine-specific demethylase 1 (LSD1) downregulation, induced by small interfering RNA (siRNA) transfection, on the proliferation, colony formation, migration and invasion of the papillary thyroid carcinoma K1 cell line. The siRNA targeting LSD1 and scrambled non-targeting siRNA were each transfected into papillary thyroid carcinoma K1 cells. Downregulation of LSD1 mRNA and protein level was evaluated by reverse transcription-quantitative polymerase chain reaction, and immunocytochemical (ICC) analysis and western blotting, respectively. A Cell Counting kit-8 assay was applied to estimate the effect of LSD1-siRNA on cell growth. Migration and invasion abilities were estimated by Transwell chamber assay. A soft agar colony formation assay was performed to estimate the effect of LSD1-siRNA on tumorigenicity in vitro. ICC data showed that LSD1 protein was strongly expressed in the blank and control K1 cells compared with the LSD1-siRNA cells (F=15.192, P<0.01). Compared with the control cells, cells transfected with siRNA targeting LSD1 exhibited significant downregulation of LSD1 mRNA (t=6.845, P<0.01) and protein (F=53.764, P<0.01) levels. siRNA targeting LSD1 also downregulated cell proliferation following transfection for 24, 48 and 72 h (t=4.777, P<0.001; t=3.302, P=0.003; and t=3.017, P=0.006, respectively). Compared with the control group, the amount of cell invasion was gradually reduced in the LSD1-siRNA group (t=12.301, P<0.01). The number of migrating cells was significantly higher in the negative control group compared with the LSD1-siRNA group (t=7.911, P<0.01), and the ability of colony formation in the LSD1-siRNA cells was notably reduced in the soft agar formation assay (t=3.612, P=0.005). siRNA targeting LSD1 efficiently inhibits the proliferation, colony formation, migration and invasion of papillary thyroid carcinoma K1 cells.

19.
Oncol Lett ; 10(6): 3393-3398, 2015 Dec.
Article En | MEDLINE | ID: mdl-26788140

In order to estimate the effects of small interfering RNA (siRNA) targeting retinoblastoma binding protein 2 (RBP2) on the proliferation, expression, invasion, migration and tumorigenicity abilities of papillary thyroid carcinoma K1 cells, siRNA targeting RBP2 (RBP2-siRNA) and negative control siRNA were transfected into K1 cells. The mRNA levels of RBP2 in the transfected cells were estimated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the protein levels of RBP2 in these cells were evaluated by western blot analysis and immunocytochemical (ICC) analyses. The growth, tumorigenicity, migration and invasion abilities of the transfected cells were measured by Cell Counting Kit-8 (CCK-8), soft agar colony formation and transwell chamber assay, respectively. The ICC results demonstrated that the protein expression levels of RBP2 were lower in the RBP2-siRNA-transfected cells than in the blank and control cells (analysis of variance, F=26.754, P<0.01). RBP2-siRNA downregulated RBP2 at the mRNA (t=8.869) and protein level (F=60.835) (P=0.000 vs. control cells). In addition, the transfection of RBP2-siRNA into K1 cells also suppressed cell proliferation at 24, 48 and 72 h post-transfection (t=7.650, P<0.01; t=2.606, P=0.016; and t=2.377, P=0.027, respectively). Compared with the control group, the number of invasive and migrated cells were significantly reduced in the RBP2-siRNA-transfected group (t=4.774 and t=6.366, respectively; P<0.01). Furthermore, the tumorigenic potential of the cells transfected with RBP2-siRNA was markedly reduced, as indicated by the soft agar formation assay (t=2.749, P=0.014 vs. control cells). In conclusion, the transfection of RBP2-siRNA into papillary thyroid carcinoma K1 cells suppressed the expression of RBP2 in these cells, and reduced their proliferation, invasion, migration and tumorigenic potential. Therefore, targeting RBP2 may be an efficient approach to control thyroid carcinoma.

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