HERC4 modulates ovarian cancer cell proliferation by regulating SMO-elicited hedgehog signaling.

BACKGROUND: HERC4 has been reported to have functions in several types of tumors, but its roles in ovarian cancer have not been studied yet. METHODS: Primary tissues from ovarian cancer patients and cell lines were collected for real-time PCR. Kaplan-Meier Plotter was used to predict the prognosis of ovarian cancer patients. HERC4 was overexpressed in cells by lentivirus, and CCK-8 assay was performed to evaluate cell viability. Real-time PCR and Western blot were carried out to analyze the mRNA and protein expression, respectively. Xenograft tumor models were established to analyze HERC4 function in vivo. RESULTS: Firstly, we found that HERC4 was significantly downregulated in ovarian cancer. We then found that ovarian cancer patients with high HERC4 expression had significantly higher overall survival and progression-free survival rates compared with patients with low expression. Then, HERC4 was overexpressed in ovarian cancer cells, and we found that overexpression of HERC4 significantly inhibited ovarian cancer cell growth, as well as the expression of the target protein SMO, and the key proteins in the downstream hedgehog signaling pathway. Finally, the xenograft tumor models revealed that overexpression of HERC4 significantly inhibited tumor growth in vivo. CONCLUSIONS: Overall, these results indicate that overexpression of HERC4 inhibits cell proliferation of ovarian cancer in vitro and in vivo, suggesting that HERC4 may serve as an effective target for the treatment of ovarian cancer.

Analysis of the Correlation between Nutritional Status and Quality of Life of Patients with Gynaecological Ovarian Cancer during Postoperative Chemotherapy.

Ovarian cancer mortality is on the rise in China. Surgery followed by adjuvant chemotherapy is the most extensively used treatment for tumour recovery. An excellent nutritional condition prior and throughout treatment serves to improve the quality of life and, as a result, the treatment result. The goal of this research was how diet affected the functioning standard of those living in carcinoma who were receiving postoperative treatment. BMI was utilised to evaluate nutrition, accompanied by albuminemia, prealbuminemia, and serum C-reactive protein, that is used to evaluate excessive catabolism. The QLQ-C30 questionnaire assessed standard of living. The performance status of the patient is decided with the help of the WHO performance scale for cancer patients. The study identified the statistically significant relationship between the performance status and hypercatabolism in the global health (quality of life) of the patient. While body mass index is often considered as a standard for assessment of nutritional status, it has affected only the cognitive function of the patient. In this study, we have concluded that in addition to direct measurement of the BMI, other clinical parameters such as serum CRP should be considered to get a better outcome of chemotherapy.

Regulation of Transcription Factor YAP-TEAD by Non-coding RNA LINC00857 and the Inhibitory Effects on Ovarian Cancer Cell Proliferation.

This study was aimed to explore the expression and mechanism of the transcription factor YAP-TEAD in the Hippo signaling pathway under the regulation of non-coding Ribonucleic Acid (RNA) LINC00857 in the proliferation of ovarian cancer cells, so as to provide a scientific research basis for clinical diagnosis and treatment of ovarian cancer. In the study, the ovarian cancer cell lines (BT 549) were rolled into a control group (normal culture-defined as BT549/NC) and a response group (transfected with non-coding RNA LINC00857 cultured cells-defined as BT 549YAP cells). The expression and proliferation ability of the transcription factor YAP-TEAD in the two groups of cancer cells were analyzed and compared. The results showed that the YAP-TEAD expression rate was the highest in Bt549 cells; the YAP content grade (0.18) in BT 549-YAP cells was lower than BT 549/NC (0.2) after transfection (P< 0.05); and the apoptotic rate of the response group (80%) was higher than that of the control group (25%) after the intervention. With the extension of culture time, the expression of CCN1 mRNA decreased (P< 0.05), and CCN2 mRNA increased (P< 0.05). After 12, 24, 36, and 48 hours, the apoptosis rate of the reaction group at different time points was higher than that of the control group (P< 0.01). When YAP-TEAD was down-regulated, the in vitro proliferation ability of BT 549-YAP cells was weakened compared with BT 549/NC and parental cells. It was concluded that the non-coding RNA LINC00857 can target the transcription factor YAP-TEAD in the Hippo signaling pathway to decrease its expression, thus inhibiting the proliferation, migration, and invasion of cancer cells, and promoting cell apoptosis.

Down-Regulation of Casein Kinase 1α Contributes to Endometriosis through Phosphatase and Tensin Homolog/Autophagy-Related 7-Mediated Autophagy.

The present study aimed to explore the roles of casein kinase 1α (CK1α) in endometriosis and its underlying mechanisms. Endometrial specimen were collected from the patients and healthy volunteers. The expression patterns of CK1α, phosphatase and tensin homolog (PTEN), and autophagy-related proteins were determined using immunohistochemistry staining, Western blot analysis, and quantitative RT-PCR. Besides, the CK1α-overexpressing cells and PTEN knockdown cells were constructed in the endometrial stromal cells isolated from endometriosis patients. In addition, the cells were transfected with pcDNA3.1-CK1α or pcDNA3.1-CK1α plus siRNA- PTEN. The expressions of CK1α, PTEN, and autophagy-related proteins were determined using Western blot and quantitative RT-PCR. The expressions of CK1α and autophagy-related 7 (Atg7) were significantly decreased in the ectopic endometrium compared with the eutopic endometrium. Spearman rank correlation analysis revealed positive correlations between CK1α and PTEN, CK1α and Atg7, and PTEN and Atg7. In addition, CK1α, PTEN, and autophagy-related proteins were down-regulated in ectopic endometrium. Interestingly, overexpression of CK1α significantly increased the expressions of autophagy-related proteins, whereas the protein expression of autophagy-related proteins was decreased with PTEN knock-down. CK1α regulated PTEN/Atg7-mediated autophagy in endometriosis.

Integration of Global and Local Features for Specular Reflection Inpainting in Colposcopic Images.

Objective: To explore an inpainting method that can balance texture details and visual observability to eliminate the specular reflection (SR) regions in the colposcopic image, thus improving the accuracy of clinical diagnosis for cervical cancer. Methods: (1) To ensure smoothness, Gaussian Blur and filling methods are applied to the global image. (2) Striving to preserve the anatomical texture details of the colposcopic image as much as possible, the exemplar-based method is applied to local blocks. (3) The colposcopic images inpainted in the previous two steps are integrated, so that important information of non-SR regions is preserved based on eliminating SR regions. Results: In the subjective visual assessment of inpainting results, the average of 3.55 ranks first in the five comparison sets. As to the clinical test, comparing the diagnosis results of 6 physicians before and after eliminating SR regions, the average accuracy of two kinds of classifications increased by 1.44% and 2.03%, respectively. Conclusions: This method can effectively eliminate the SR regions in the colposcopy image and present a satisfactory visual effect. Significance. As a preprocessing method for computer-aided diagnosis systems, it can also improve physicians' accuracy in clinical diagnosis.

Effect of introducing human papillomavirus genotyping into real-world screening on cervical cancer screening in China: a retrospective population-based cohort study.

BACKGROUND: China's Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). METHODS: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. RESULTS: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p < 0.001); the rate of colposcopy referral was higher (10.87% versus 6.64%; p < 0.001); and the hazard ratio of CIN2+ diagnosis was 1.64 (95% confidence interval, 1.43-1.88; p < 0.001) after controlling for health insurance status and age. The total costs of the first round of screening (US$66,609 versus US$65,226; p = 0.293) were similar during the two periods. Higher screening coverage (25.95% versus 25.19%; p = 0.007), higher compliance with age recommendations (92.70% versus 91.69%; p = 0.001), lower over-screening (4.92% versus 10.15%; p < 0.001), and reduced unqualified samples (cytology: 1.48% versus 1.73%, p = 0.099; HR-HPV: 0.57% versus 1.34%, p < 0.001) were observed in the HR-HPV genotyping period. CONCLUSIONS: Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China.

HMGB1 Mediated Inflammation and Autophagy Contribute to Endometriosis.

Aim: High mobility group box (HMGB)-1 has been implicated in endometriosis due to the important regulatory roles of inflammation in endometriosis. The aim of the present study was to explore the roles of HMGB-1 in endometriosis and to elucidate the underlying mechanism. Methods: Endometrial specimens were collected from women with endometriosis and healthy volunteers. Immunohistochemistry staining was used to determine the expression patterns and localization of HMGB-1 in the normal, eutopic and ectopic endometrial tissues. Western blotting and qRT-PCR were used to determine the mRNA and protein levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1ß], autophagy-related markers [beclin-1, autophagy-related (atg)13, microtubule-associated protein light chain (LC)3-I, LC-II and p62] and HMGB-1, respectively. Spearman's rank correlation analysis was employed to investigate the correlation between HMGB-1 with inflammatory cytokines and beclin-1. Besides, human endometrial stromal cells (HESCs) were isolated from ectopic endometrium and subsequently transfected with shRNA against HMGB-1. After the transfected cells were subjected to hypoxia, ELISA was used to determine the levels of HMGB-1 and inflammatory cytokines in the cell supernatant. Western blotting was used to determine the expression levels of autophagy-related markers in the cells. Results: Positive correlations were observed between HMGB-1 and the inflammatory cytokines. In addition, a positive correlation was also identified between HMGB-1 and beclin-1 in the ectopic endometrium. Further results demonstrated that autophagy-related markers beclin-1, atg13 and p62 were significantly upregulated in the ectopic endometrium. In addition, HMGB-1 knockdown suppressed the levels of inflammatory cytokines IL-6, TNF-α and IL-1ß and autophagy-related markers beclin-1 and atg13, while upregulated p62 in HESCs under hypoxic condition. Conclusion: Knockdown of HMGB-1 under hypoxic condition regulated inflammatory cytokines and autophagy-related markers. HMGB-1 might contribute to the development of endometriosis in part through regulating inflammatory response and autophagy.

Crocin exhibits an antihypertensive effect in a rat model of gestational hypertension and activates the Nrf-2/HO-1 signaling pathway.

Gestational hypertension is a leading cause of both prenatal and maternal mortality and morbidity; however, there have been rather limited advances in the management of gestational hypertension in recent years. There has been evidence supporting the antihypertensive properties of crocin, but the specific mechanism is still unclear. N-Nitro-L-arginine methyl ester (L-NAME) was employed to establish a rat model with a preeclampsia-like phenotype, particularly gestational hypertension. Enzyme-linked immunosorbent assays were conducted to determine the levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1); the levels of the circulating cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α; and oxidative stress factors. Quantitative RT-PCR assays were performed to assess the transcript levels of various cytokines in the placenta, and western blot assays were carried out to evaluate the protein levels of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2-like 2 (Nrf-2). Treatment with crocin reduced the blood pressure of rats with gestational hypertension, which was accompanied by suppressed circulating levels of PlGF and sFlt-1. Crocin further alleviated the inflammatory signals and oxidative stress in the serum, as well as in placental tissues, in rats with L-NAME-induced hypertension. Crocin treatment also improved pregnancy outcomes in terms of fetal survival, fetal weight, and the fetal/placental weight ratio. Finally, in hypertension elicited by L-NAME, crocin stimulated the placental Nrf-2/HO-1 pathway. Crocin alleviated inflammatory and oxidative stress in placental tissues, thereby protecting against gestational hypertension, one of the major phenotypes of preeclampsia, and activated the Nrf-2/HO-1 pathway.

Long non-coding RNA TUG1 sponges microRNA-381-3p to facilitate cell viability and attenuate apoptosis in cervical cancer by elevating MDM2 expression.

OBJECTIVE: Based on the theory that long non-coding RNAs (lncRNAs) sponge microRNAs (miRNAs) to engage in cervical cancer development, this work was set out to investigate the possible role of lncRNA taurine upregulated gene 1 (TUG1) and miR-381-3p in the development of cervical cancer. METHODS: TUG1, miR-381-3p and murine double minute 2 (MDM2) expression were measured in cervical cancer tissues and cells. The nexus between TUG1 and clinicopathological features of cervical cancer was discussed. The biological functions of TUG1, miR-381-3p and MDM2 on cervical cancer cell process were interpreted via gain- and loss-of-function experiments. Also, tumor xenograft in nude mice was conducted in vivo. The interactions between TUG1, miR-381-3p and MDM2 were identified. RESULTS: TUG1 and MDM2 raised while miR-381-3p reduced in cervical cancer. TUG1 expression was related to tumor size, differentiation, international federation of gynecology and obstetrics stage and lymph node metastasis of cervical cancer. Restored miR-381-3p, depleted TUG1 or reduced MDM2 decreased viability, colony-forming, migration and invasion abilities, and facilitated apoptosis of cervical cancer cells. Xenografted tumors grew slowly upon injection with restored miR-381-3p and depleted TUG1. TUG1 bound to miR-381-3p and miR-381-3p targeted MDM2. CONCLUSION: On all accounts, this present study provides evidence that silencing TUG1 depressed cervical cancer cell progression through miR-381-3p/MDM2 axis, highlighting a theoretical basis for cervical cancer treatment.

LncRNA LINC00857 regulates the progression and glycolysis in ovarian cancer by modulating the Hippo signaling pathway.

Ovarian cancer is one of the most common gynecological cancers with high morbidity and mortality, which seriously endangers women's health and quality of life. Long noncoding RNAs (lncRNAs) can regulate the progression of cancers, including ovarian cancer. LINC00857 (long intergenic non-protein coding RNA 857) has been discovered to be a crucial factor in the regulation of cancer development. Nevertheless, the specific functions and mechanisms of LINC00857 in ovarian cancer remain unclear. The Hippo signaling pathway can involve in cancer progression. In our research, we aimed to investigate the correlation of LINC00857 and Hippo pathway. Quantitative real-time polymerase chain reaction assay was utilized to test the expression of LINC00857 in ovarian cancer tissues and cells. Functional experiments revealed that LINC00857 silencing led to the inhibition on cell proliferation, migration, invasion, and glycolysis but accelerated cell apoptosis in ovarian cancer. Mechanism experiments, including RNA immunoprecipitation, RNA pull-down, and luciferase reporter experiments demonstrated that LINC00857 could regulate YAP1 (Yes1 associated transcriptional regulator) by competitively binding to miR-486-5p in ovarian cancer. In a word, this study unveiled that LINC00857 regulates YAP1 by competitively binding to miR-486-5p and accelerates ovarian cancer progression.

Sulforaphane Attenuates Endometriosis in Rat Models Through Inhibiting PI3K/Akt Signaling Pathway.

Sulforaphane exerts anti-inflammatory activity in inflammatory diseases. The endometriosis (EM) is accompanied by chronic inflammation. The present study aims to explore the therapeutic effects of sulforaphane on EM and its underlying mechanism. An EM rat model was established by transplantation of autologous fragments. The rats were intragastrically administered sulforaphane (5 mg/kg, 15 mg/kg, and 30 mg/kg) for 3 weeks. The volumes of endometriotic foci and adhesion score were calculated at the end of the experiment. Levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA). Expressions of VEGF, B-cell lymphoma/leukemia 2 (Bcl-2), Bax, cleaved caspase-3, PI3K, and Akt in endometrial tissue were determined by Western blotting. Relative expressions of PI3K and Akt were determined by quantitative polymerase chain reaction. Posttreatment of sulforaphane dose-dependently decreased the volumes of endometriotic foci and adhesion score in EM model. Additionally, posttreatment of sulforaphane inhibited levels of IL-6, IL-10, TNF-α, IFN-γ, and VEGF in peritoneal fluid and plasma. Posttreatment of sulforaphane regulated the expressions of VEGF, bcl-2, Bax, and cleaved Caspase-3 in EM model. The underlying mechanism revealed that sulforaphane attenuated EM in the rat model by inhibition of PI3K/Akt signaling pathway.