MicroRNA­491­5p inhibits trophoblast cell migration and invasion through targeting matrix metalloproteinase­9 in preeclampsia.

Insufficient invasion of trophoblasts is correlated with the development of preeclampsia (PE). MicroRNA (miR)­491­5p has been reported to be implicated in human cancer cell invasion; however, whether miR­491­5p is involved in the development of PE remains largely unclear. The aim of the present study was to investigate the role of miR­491­5p in trophoblastic invasion in vitro and to determine its underlying mechanism of action. The expression levels of miR­491­5p were validated using reverse transcription­quantitative PCR. The effects of miR­491­5p on trophoblast cell invasion were evaluated in vitro. Then, the association between miR­491­5p and its downstream target was investigated in both cell lines and clinical specimens. miR­491­5p expression levels were observed to be significantly increased in the placental tissues from patients with PE. The invasive capacity of HTR­8/SVneo trophoblast cells was suppressed following the upregulation of miR­491­5p and increased following the inhibition of miR­491­5p. Matrix metalloproteinase­9 (MMP­9), a well­known regulator of trophoblast cell invasion, was discovered to be a direct target of miR­491­5p in HTR­8/SVneo trophoblast cells. Moreover, miR­491­5p expression levels were found to be inversely correlated with MMP­9 expression levels in placental tissues from patients with PE. The overexpression of MMP­9 partly attenuated the inhibitory effects of miR­491­5p on HTR­8/SVneo trophoblast cells invasion. Collectively, these findings suggested that the aberrant expression of miR­491­5p may contribute to PE through suppressing trophoblast invasion, thus highlighting the novel roles of miR­491­5p in the molecular pathogenesis of PE. The present study also showed that the miR­491­5p/MMP­9 axis may be an effective biomarker or a viable drug target for therapeutic intervention in PE.

Long-Chain Non-Coding RNA SNHG3 Promotes the Growth of Ovarian Cancer Cells by Targeting miR-339-5p/TRPC3 Axis.

BACKGROUND: Long-chain non-coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is reportedly overexpressed in malignant tumors, but its regulatory role in human ovarian cancer (OC) is not fully understood. METHODS: A qRT-PCR assay was carried out to detect the level of SNHG3 in OC tissues, serum and cells, a CCK-8 assay to measure the proliferation of OC cells, a transwell assay to measure the invasion and migration of OC cells, and a flow cytometry to detect the cell cycle distribution and apoptosis rate of OC cells. In addition, in vivo experiment was also conducted to determine the effect of SNHG3 on the growth of OC cells. RESULTS: SNHG3 was overexpressed in OC tissues, serum, and cells, and the overexpression in serum indicated a poor prognosis of patients. It was also found that knockdown of SNHG3 could inhibit the malignant phenotypes of OC cells, cause G1/G0 cell cycle arrest, and intensify apoptosis. Furthermore, in in vitro experiments, the growth ability of OC cells was inhibited under knockdown of SNHG3. Assays for relationship verification showed that SNHG3 regulated the expression of miR-339-5p and the canonical transient receptor potential 3 (TRPC3), and the rescue experiment revealed that co-transfection of si-SNHG3+miR-339-5p-inhibitor or si-SNHG3+pcDNA3.1-TRPC3 could reverse the effects of knockdown of SNHG3 on the biological behavior of OC cells. CONCLUSION: SNHG3 can be adopted as a marker for diagnosis and prognosis evaluation of OC and it plays a role in the progression of OC by enabling the miR-339-5p sponge to regulate TRPC3 expression.

MiR-93 blocks cell cycle progression and promotes apoptosis in uterine leiomyoma cells by targeting CCND1.

Uterine leiomyoma (UL) is the most common type of benign tumor in the women's reproductive system. A number of genes has been found to play an important role in the initiation and progression of UL, including miRNAs. In this study, our results exhibited that miR-93, a member of mir-106b-25 cluster, significantly reduced the cell viability, promoted cell cycle arrest, caused apoptosis, and inhibited migration in UL cells (p < .01). Moreover, our results have provided experimental evidence that miR-93 regulated the biological functions of UL cells by targeting CCND1.

MicroRNA­142­3p inhibits trophoblast cell migration and invasion by disrupting the TGF­ß1/Smad3 signaling pathway.

Insufficient invasion of trophoblasts is known to be associated with preeclampsia (PE) development. Recently, microRNAs (miRNAs) have been reported to serve important roles in the pathogenesis of PE. However, little is known regarding the regulation of trophoblastic invasion by miRNAs. The aim of the present study was to explore the role of miRNAs in trophoblastic invasion and the underlying molecular mechanism. Using a miRNA microarray, miRNAs putatively involved in the pathophysiology of PE were examined between normal and preeclamptic placentas. Validation analysis of miR­142­3p level in placenta specimens was performed using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Then, the regulation of miR­142­3p on trophoblast cells migration and invasion was evaluated using wound healing and transwell migration assays. Furthermore, the target gene of miR­142­3p and the downstream signaling pathway were also investigated. Microarray analysis and RT­qPCR revealed that miR­142­3p was significantly upregulated in placenta specimens from patients with PE. Its overexpression inhibited trophoblast cell invasion and migration, whereas its knockdown enhanced trophoblast cell invasion and migration. In addition, overexpression of miR­142­3p inhibited the mRNA expression and the activities of matrix metalloproteinase­2 (MMP2) and MMP9, which are closely associated with cell invasion and migration, while inhibition of miR­142­3p had the opposite result. Subsequent analyses demonstrated that transforming growth factor­ß1 (TGF­ß1) was a direct and functional target of miR­142­3p. Notably, the knockdown of TGF­ß1 effectively reversed the enhancement of miR­142­3p inhibitor on trophoblast cell invasion and migration. Finally, the present study confirmed that miR­142­3p inhibitor enhanced cell invasion and migration by reactivating the TGF­ß1/Smad3 signaling pathway. Taken together, the results of the present study suggest that miR­142­3p may serve an important role in human placental development by suppressing trophoblast cell invasion and migration through disruption of the TGF­ß1/smad3 signaling pathway, suggesting that knockdown of miR­142­3p may provide a novel therapy for PE.

Prognosis in Pregnant Females With Systemic Lupus Erythematosus.

OBJECTIVES: This study aims to analyze the relationship between pregnancy and lupus, and explore the risk factors that adversely affect maternal and infant outcomes. PATIENTS AND METHODS: The pregnancy outcomes in 112 pregnant females (mean age 24.3±2.8 years; range 20 to 35 years) with systemic lupus erythematosus (SLE) were retrospectively analyzed. Pregnancy outcomes before and after pregnancy were compared, and the associations with lupus nephritis, positive anti-Ro/SSA antibody, positive La/SSB antibody, complement 3 and complement 4, high blood pressure, positive anti- cardiolipin (aCL) antibody, Raynaud's phenomenon, and lupus recurrence were evaluated. Factors contributing to adverse outcomes were analyzed using multinomial logistic regression. RESULTS: The live birth rate in females diagnosed with SLE before a pregnancy was higher than that in females diagnosed with SLE after a pregnancy. The fetal mortality rate in females diagnosed with SLE after a pregnancy was higher than that in females diagnosed with SLE before a pregnancy. However, the abortion rate in females diagnosed with SLE before a pregnancy was also significantly higher than that in females diagnosed with SLE after a pregnancy. The incidence of preterm birth in females diagnosed with SLE after a pregnancy was higher than that in females diagnosed with SLE after a pregnancy. Preterm birth was more likely to occur in females positive for Ro/SSA antibody. Patients with hypertension and Raynaud's phenomenon had a higher risk of intrauterine growth retardation. In addition, the presence of aCL antibody was associated with pregnancy loss. Multinomial logistic regression analysis showed that many factors might be associated with adverse pregnancy outcomes, including lupus nephritis, positive Ro/SSA antibody, positive La/SSB antibody, complement 3 and complement 4, positive aCL antibody, lupus recurrence, hypertension, and Raynaud's phenomenon. CONCLUSION: Lupus nephritis, Ro/SSA antibody, aCL antibody, hypertension, Raynaud's phenomenon, and lupus recurrence are important factors associated with adverse pregnancy outcomes.

Carboplatin-docetaxel-induced activity against ovarian cancer is dependent on up-regulated lncRNA PVT1.

Ovarian cancer is the fourth most ordinary cause of cancer-related deaths in women. In recent, combination chemotherapy with carboplatin and docetaxel was developed as first-line drug to treat ovarian carcinoma. However, the detailed molecular mechanism, which accounts for the cells to apoptosis induced by administration of carboplatin and docetaxel, was unrecognized. In present study, we provide the mechanistic link between mixture of carboplatin plus docetaxel and its anticancer activity. Primarily, a majority of 30 cancer-related long non-coding RNA (lncRNA) showed differential alteration in carboplatin-docetaxel-treated 3AO cells. Among six up-regulating lncRNAs, we screened out carboplatin-docetaxel-induced lncRNA PVT1 which may be a central downstream target of carboplatin plus docetaxel because expression of PVT1 positively correlates with anticancer action of carboplatin plus docetaxel. Besides, p53 and tissue inhibitor of matrix metalloproteinases-1 (TIMP1) were mediated by lncRNA PVT1, which may explain partially the anticancer activity of lncRNA PVT1. Collectively, we have identified a potential mechanism by which PVT1 regulated by carboplatin plus docetaxel contributes to the carboplatin-docetaxel-induced anticancer action in ovarian cancer. These discoveries also give proof of the potential of PVT1 as significant downstream targets for therapeutic intervention in ovarian cancer.

Changes of TIZ expression in epithelial ovarian cancer cells.

OBJECTIVE: To study the change of TIZ expression in epithelial ovarian cancer cells. METHODS: HO8910 cells were transinfected with siRNA to inhibit the expression of TIZ. pcDNA3.1-TIZ vectors were combined to increase the TIZ expression level. The cell viability, colony forming efficiency and cycle distribution of HO8910, HO8910/NC, HO8910/pcDNA3.1-NC, HO8910/TIZ-573 and H08910/pcDNA3.1-TIZ were compared, and the invasion rate, migration rate and adhesion rate between 5 groups of cells were compared. RESULTS: Compared with those of HO8910, HO8910/NC and HO8910/pcDNA3.1-NC, the cell viability, colony forming efficiency and cell cycle distribution of HO8910/TIZ-573 were increased, while the indexes of H08910/pcDNA3.1-NC were decreased with statistical significant difference (P<0.05). There was no statistical significant difference in the invasion rate, migration rate and adhesion rate between 5 groups of cells (P>0.05). CONCLUSIONS: The expression of TIZ can inhibit the proliferation of epithelial ovarian cancer cells.

Overexpression of long non-coding RNA PVT1 in ovarian cancer cells promotes cisplatin resistance by regulating apoptotic pathways.

Ovarian cancer is the most lethal gynecologic malignancy. Cisplatin is a very effective cancer chemotherapy drug, but cisplatin resistance is a crucial problem of therapy failure. Overexpression of PVT1 has been demonstrated in ovarian cancer. The mRNA level of PVT1 in ovarian cancer tissues of cisplatin-resistant patients and cisplatin-sensitive patients, cisplatin-resistant cells SKOV-3/DDP and A2780/DDP, cisplatin-sensitive cells SKOV-3 and A2780 were determined by qRT-PCR. The influence of the knockdown or overexpression of PVT1 on cisplatin resistance was measured by measuring the cytotoxicity of cisplatin and the apoptotic rate of ovarian cancer cells was detected by CCK-8 assay and flow cytometry, respectively. The mRNA levels and protein expression of TGF-ß1, Smad4, p-Smad4 and Caspase-3 in apoptotic pathways were determined. The mRNA level of PVT1 was significantly higher in ovarian cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. SKOV-3/DDP and A2780/DDP cell viability and the percentage of apoptotic cells after transfection with PVT-1 siRNA and treated with cisplatin was markedly lower and higher than the control, respectively. Moreover, the overexpression of PVT1 exhibited the anti-apoptotic property in SKOV-3 and A2780 cells after transfection with LV-PVT1-GFP and treated with cisplatin. The mRNA levels and protein expression of TGF-ß1, p-Smad4 and Caspase-3 were much higher in cisplatin-resistant cells transfected with siPVT1. Overexpression of LncRNA PVT1 in ovarian cancer promotes cisplatin resistance by regulating apoptotic pathways.

Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced ovarian epithelial carcinoma.

BACKGROUND: The purpose of the study was to evaluate the role of neoadjuvant chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries in treating patients with advanced ovarian epithelial carcinoma. METHODS: Forty-two patients with advanced ovarian epithelial carcinoma (study group) were treated via the anterior branches of the bilateral internal iliac arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based combination chemotherapy. Primary cytoreductive surgery was performed in 43 patients with advanced ovarian epithelial carcinoma (control group), and then followed by 8 courses of adjuvant platinum-based combination chemotherapy. The rate of optimal cytoreductive surgery, survival rate, blood loss during operation and operative time were investigated in the two groups. Statistical significance was assessed using Student's t test, the Chi-square test and the log-rank test. RESULTS: In the study group, the rate of optimum debulking after platinum-based chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries was 71.43% (30/42) (chi(2) = 10.06, P < 0.005), and 9 (21.43%) of the 42 patients showed no gross residual disease after surgery. Blood loss and operative time were significantly decreased in the study group as compared with those in the control group (665.24 +/- 37.61 ml: 849.31 +/- 41.20 ml, t(1) = 33.21, P(1) < 0.001; 4.23 +/- 0.21 hours: 6.15 +/- 0.38 hours, t(2) = 28.92, P(2) < 0.01). In the study group, the mean survival time and the median overall survival were 33.66 months (95% CI, 24.73 to 42.58) and 26.00 months (95% CI, 19.22 to 32.78), respectively. The median disease-free interval was 18.20 months. In the control group, the mean survival time and the median overall survival were 32.38 months (95% CI, 24.92 to 39.84) and 25.00 months (95% CI, 22.80 to 27.20), respectively. The median disease-free interval was 14.20 months. The overall survival rates were not significantly different between the two groups (chi(2) = 6.48, P > 0.05). CONCLUSIONS: Neoadjuvant platinum-based combination chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries is an alternative treatment for patients with advanced ovarian epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low. The treatment can reduce blood loss, decrease operative time, and increase the rate of optimal cytoreductive surgery; but the median survival can't be improved significantly.