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BACKGROUND: Primary lymphoma of the female genital tract (PLFGT) is a rare malignant tumor in the female reproductive system, with a low incidence and few clinical reports. The aim of this study is to report our institutional experience with this rare malignancy and emphasize the need for increasing the awareness about PLFGT presenting with gynecologic symptoms. METHODS: The medical records of patients diagnosed with PLFGT from March 2014 to November 2022 in the First Affiliated Hospital of Wannan Medical College were reviewed. Histological classification and staging were based on the World Health Organization and Ann Arbor systems, respectively. RESULTS: There were 13 patients with diagnosis of PLFGT and the median length of follow-up was 31 months (0-102 months). The main clinical symptoms included postmenopausal vaginal bleeding, pelvic mass and abdominal pain. Serum LDH increased in 10 patients and serum CA125 elevated in 2 patients. The tumor of ovarian or uterine presented as solid masses in CT or MRI, and ascites was rare. The histological subtypes were diffuse large B-cell (n = 12) and follicular (n = 1) lymphoma. Tumors were located in ovary (n = 8), uterus (n = 3), and cervix (n = 2). According to the Ann Arbor staging system, 6 cases were classified as stage II and 7 cases were classified as stage IV, respectively. A total of 10 patients underwent surgery. Combination chemotherapy was used in 10 patients. Eight patients had tumor-free survival, 1 patient had recurrent disease, 3 patients died and 1 patient lost to follow-up. The median survival time was 32 months (1-102 months). CONCLUSION: PLFGT usually presents as gynecological symptoms and solid masses in pelvis. Surgery or biopsy was the way to obtain the pathologic diagnosis, and combination chemotherapy is the efficient method for PLFGT. Making an accurate preoperative diagnosis is of paramount importance to avoid radical gynecologic surgery.
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Neoplasias dos Genitais Femininos , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Genitália Feminina , Procedimentos Cirúrgicos em Ginecologia , Estadiamento de NeoplasiasRESUMO
BACKGROUND: There is evidence for an association between the gut microbiome and endometriosis. However, their causal relationship and the mediating role of lipid metabolism remain unclear. METHODS: Using genome-wide association study (GWAS) data, we conducted a bidirectional Mendelian randomization (MR) analysis to investigate the causal relationships between gut microbiome and endometriosis. The inverse variance weighted (IVW) method was used as the primary model, with other MR models used for comparison. Sensitivity analysis based on different statistical assumptions was used to evaluate whether the results were robust. A two-step MR analysis was further conducted to explore the mediating effects of lipids, by integrating univariable MR and the multivariate MR method based on the Bayesian model averaging method (MR-BMA). RESULTS: We identified four possible intestinal bacteria genera associated with the risk of endometriosis through the IVW method, including Eubacterium ruminantium group (odds ratio [OR] = 0.881, 95% CI: 0.795-0.976, P = 0.015), Anaerotruncus (OR = 1.252, 95% CI: 1.028-1.525, P = 0.025), Olsenella (OR = 1.110, 95% CI: 1.007-1.223, P = 0.036), and Oscillospira (OR = 1.215, 95% CI: 1.014-1.456, P = 0.035). The further two-step MR analysis identified that the effect of Olsenella on endometriosis was mediated by triglycerides (proportion mediated: 3.3%; 95% CI = 1.5-5.1%). CONCLUSION: This MR study found evidence for specific gut microbiomes associated with the risk of endometriosis, which might partially be mediated by triglycerides.
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Endometriose , Microbioma Gastrointestinal , Feminino , Humanos , Microbioma Gastrointestinal/genética , Endometriose/genética , Teorema de Bayes , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Lipídeos , TriglicerídeosRESUMO
STUDY OBJECTIVE: To evaluate high-intensity focused ultrasound (HIFU) ablation therapy for abdominal wall endometriosis (AWE). DESIGN: A retrospective study. SETTING: Gynecologic department of a teaching hospital in China. PATIENTS: Thirty patients with AWE were treated from May 2013 to December 2015. INTERVENTIONS: Thirteen patients were treated with HIFU ablation and 17 patients with surgical resection. MEASUREMENTS AND MAIN RESULTS: Color Doppler ultrasonography and magnetic resonance imaging were used to observe the lesions before and after treatment. In addition, recovery time, complications, and adverse reactions of the 2 groups were compared. Menstrual pain was relieved after treatment in all 30 patients. After treatment, the lesions in patients who underwent HIFU ablation decreased gradually, and there was no recurrence. Symptoms recurred in 1 patient in the surgery group 12 months after surgery. The post-treatment hospital length of stay of the HIFU ablation group (1.00 ± 0 days) was significantly shorter than that of the surgical group (5.23 ± 1.24 days; p <.001). The incidence of fever (0% vs 11.8%; pâ¯=â¯.049) and complications of the urinary system (7.7% vs 17.6%; pâ¯=â¯.043) in the HIFU ablation group were significantly lower than that of the surgical group. CONCLUSIONS: HIFU ablation therapy is a promising treatment for AWE, and further study is warranted.
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Parede Abdominal/cirurgia , Endometriose/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade , Doenças Peritoneais/cirurgia , Parede Abdominal/patologia , Adulto , China , Dismenorreia/diagnóstico , Dismenorreia/etiologia , Dismenorreia/cirurgia , Endometriose/diagnóstico , Endometriose/patologia , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Humanos , Tempo de Internação , Imageamento por Ressonância Magnética , Doenças Peritoneais/diagnóstico , Doenças Peritoneais/patologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia Doppler em CoresRESUMO
Long noncoding RNA (lncRNA) is a new class of noncoding RNA playing an indispensable role in different diseases by regulating miRNA. Our previous studies have suggested that miR-630 was decreased in patients with cervical cancer. Recently, studies have shown that lncRNA NOC2L-4.1 was abnormally expressed in patients with cervical cancer and can target miR-630. Therefore, we wanted to identify the integrated relationship between lncRNA NOC2L-4.1 and miR-630 in the pathological processes regarding cervical cancer either in vitro or in vivo. Quantitative reverse transcription-polymerase chain reaction detection shows that compared with human normal cervical epithelial cell, the expression of lncRNA NOC2L-4.1 was significantly increased and the expression of miR-630 was decreased in cell lines of cervical cancer. Moreover, luciferase reporter assay showed that miR-630 was a target of lncRNA NOC2L-4.1. The in vitro study found that downregulation of lncRNA NOC2L-4.1 suppressed cervical cancer cell migration (transwell assays) and proliferation (cell counting kit-8 and cloning formation assays). miR-630 specific inhibitor treatment reversed the inhibitory effect of lncRNA NOC2L-4.1 on cell proliferation and migration. Further studies also found that yes-associated protein 1 (YAP1) was the target of miR-630. Overexpression YAP1 suppressed miR-630 overexpression induced cell proliferation and inhibition of migration. Tumors induced by implantation of lncRNA NOC2L-4.1-knockdown Hela cells in nude mice showed that lncRNA NOC2L-4.1 silencing decreased the growth of tumors in both volume and weight by regulation of miR-630/YAP1. Taken together, our study reveals the important role of lncRNA NOC2L-4.1/miR-630/YAP1 regulatory network in cervical cancer, which provides new insights concerning the pathogenesis of cervical cancer.
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Proteínas Adaptadoras de Transdução de Sinal/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oncogenes/genética , Transdução de Sinais/genética , Neoplasias do Colo do Útero/patologia , Proteínas de Sinalização YAPRESUMO
Endometriosis is a chronic gynecological condition characterized by the presence of endometrial glands and stroma outside the uterine cavity., accounting for 7% of all female malignant tumors and 20%- 30% of malignant tumors of the female reproductive system. Multiple studies have shown that circular RNA (circRNA) has the potential to become a targeted target and marker for EM. However, the roles of circ_0001495 in EM are still unclear. Our research aims to reveal the molecular mechanism of circ_0001495 in EM. In this study, RT-PCR or western blot were conducted to determine mRNA and protein expression. cell viability, proliferation, migration, invasion, and apoptosis were assessed by CCK-8, EdU, wound healing, transwell, and flow cytometry analyses, respectively. Additionally, the targeting relationship between miR-34c-5p and circ_0001495 or E2F3 was confirmed through dual-luciferase reporter gene assay. We found significant overexpression of circ_0001495 in EM tissues and cells. Knockdown of circ_0001495 inhibited the proliferation, migration and invasion of ectopic endometrial stromal cells (EESCs) and increased cell apoptosis. Moreover, we found that circ_0001495 regulated E2F3 levels by interacting with miR-34c-5p in EESC. Furthermore, in vitro, miR-34c-5p inhibition or E2F3 overexpression could attenuate the effect of circ_0001495 silencing on EM progression. In addition, the vivo experiment demonstrated that inhibition of circ_0001495 could repress the development of endometriosis by regulating the miR-34c-5p/E2F3 axis. In conclusion, our study suggested that circ_0001495 promoted EM progression in vitro and in vivo through the miR-34c-5p/E2F3 axis, which might be a potential therapeutic target for EM.
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Fator de Transcrição E2F3 , Endometriose , MicroRNAs , RNA Circular , Feminino , Endometriose/metabolismo , Endometriose/genética , Endometriose/patologia , MicroRNAs/metabolismo , MicroRNAs/genética , Fator de Transcrição E2F3/metabolismo , Fator de Transcrição E2F3/genética , RNA Circular/metabolismo , RNA Circular/genética , Humanos , Camundongos , Animais , Proliferação de Células , Apoptose , Movimento Celular , AdultoRESUMO
[This retracts the article DOI: 10.3892/ol.2017.6210.].
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OBJECTIVE: Uterine corpus endometrial carcinoma (UCEC), a kind of gynecologic malignancy, poses a significant risk to women's health. The precise mechanism underlying the development of UCEC remains elusive. Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein superfamily, was reported to be dysregulated in various illnesses, including malignant tumors. This study aimed to examine the involvement of ZNF554 in the development of UCEC. METHODS: The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay. Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection. CCK-8, wound healing, and Transwell invasion assays were employed to assess cell proliferation, migration, and invasion. Propidium iodide (PI) staining combined with fluorescence-activated cell sorting (FACS) flow cytometer was utilized to detect cell cycle distribution. qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels. Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5 (RBM5). RESULTS: The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines. Decreased expression of ZNF554 was associated with higher tumor stage, decreased overall survival, and reduced disease-free survival in UCEC. ZNF554 overexpression suppressed cell proliferation, migration, and invasion, while also inducing cell cycle arrest. In contrast, a decrease in ZNF554 expression resulted in the opposite effect. Mechanistically, ZNF554 transcriptionally regulated RBM5, leading to the deactivation of the Wingless (WNT)/ß-catenin signaling pathway. Moreover, the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression on ß-catenin and p-glycogen synthase kinase-3ß (p-GSK-3ß). Similarly, the deliberate activation of RBM5 reduced the increase in ß-catenin and p-GSK-3ß caused by the suppression of ZNF554. In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown. Additionally, when RBM5 was overexpressed, it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels. CONCLUSION: ZNF554 functions as a tumor suppressor in UCEC. Furthermore, ZNF554 regulates UCEC progression through the RBM5/WNT/ß-catenin signaling pathway. ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.
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Neoplasias do Endométrio , Via de Sinalização Wnt , Feminino , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Supressoras de Tumor/genética , Via de Sinalização Wnt/genéticaRESUMO
Objective: To investigate the feasibility and short-term efficacy of gasless single-port laparoscopic inguinal lymphadenectomy through vulva incision (VEIL-V). Methods: The data of 9 patients diagnosed as vulvar squamous cell carcinoma who underwent single-port laparoscopic inguinal lymph node dissection through vulvectomy incision were retrospectively analyzed. And 13 patients who underwent laparoscopic inguinal lymph node dissection through lower abdominal subcutaneous approach as the control group (VEIL-H). The operation time, blood loss, numbers of unilateral lymph nodes, hospitalization time, and complications between the two groups were compared. Results: The operation time of VEIL-V was 56.11 ± 5.94 min, which were shorter than that of VEIL-H (74.62 ± 5.50 min; P = 0.013). Bleeding amount in the VEIL-H was 29.44 ± 2.56, which was significantly lower than that of the VEIL-H group (43.08 ± 4.14 ml; P = 0.021). In the two groups, the numbers of unilateral lymph nodes harvested were similar. The differences in the postoperative hospital stay, skin, and lymphatic complications were not statistically significant. Conclusion: Compared with VEIL-H, gasless single-port laparoscopic inguinal lymphadenectomy through vulva incision reduces the difficulty of operation with shorter operation time, and less blood loss, which can be a safe and mini-invasive surgical approach.
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Objective: This study aims to investigate the feasibility and short-term efficacy of single-port laparoscopic-assisted transvaginal natural cavity endoscopic sacrospinous ligament suspensions (SvNOTES). Methods: A total of 30 patients diagnosed with anterior or/and middle pelvic organ prolapse Stages III and IV underwent natural vaginal cavity (SvNOTES), and 30 patients who underwent conventional sacrospinous ligament (SSLF) were used as a control group. The operation time, blood loss, postoperative POP-Q score, length of hospital stay, and complications were compared between the two groups. Results: The operation time for SvNOTE was (60 ± 13) min, which was longer than (30 ± 15) min for SSLF (P = 0.04). However, the bleeding amount in SvNOTE was 29.44 ± 2.56, significantly lower than that in the SSLF group (80 ± 10; P = 0.02), and the postoperative hospital stay in the SvNOTE group was (4 ± 2) days, longer than (3 ± 1) days in SSLF (P = 0.02). However, there were no intraoperative complications in the SvNOTE group, whereas one ureteral injury occurred in the SSLF group; in addition, the postoperative POP-Q score was significantly better in the SvNOTE group than that in the SSLF group with increasing time (P < 0.001). Conclusion: Compared with SSLF, single-port laparoscopic sacrospinous ligament suspension via the natural vaginal cavity is visualized, greatly improving the success rate of sacrospinous ligament fixation, with less blood loss and fewer complications, arguably a safer and minimally invasive surgical approach.
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N6-methyladenosine (m6A) RNA methylation has been determined to execute crucial functions in tumorigenesis and cancer development. WT1-associated protein (WTAP) has an important "writer" role in m6A modification, and it is also a nuclear protein that colocalizes with splicing factors and plays a critical role in cell function and cancer progression. However, little is known about the role of WTAP in ovarian cancer (OC) and its mechanisms. In this study, we found for the first time that hypoxia-inducible factor (HIF)-1α could positively regulate increased expression of WTAP under hypoxia. And further results revealed that WTAP expression was closely associated with the clinicopathological features of OC, and high expression of WTAP predicted low survival rate in patients with OC. In addition, cell proliferation and invasive capacity were significantly reduced after knockdown of WTAP expression in OC cells. However, cell proliferation and invasive ability were significantly enhanced after overexpression of WTAP. Additionally, we find that WTAP interacts with DGCR8 (a crucial chip protein) to regulate the expression of microRNA-200 (miR-200) in an m6A-dependent way. Further experiments showed that the key glycolysis enzyme HK2 could be positively regulated by miR-200, which significantly affected the intracellular Warburg effect. In conclusion, this is considered uncovered that upregulation of WTAP expression by HIF-1α intercedes with miRNA processing, accelerates the Warburg impact, and advances the event and advancement of tumor, thus giving a novel viewpoint on m6A adjustment in OC movement.
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MicroRNAs , Neoplasias Ovarianas , Fatores de Processamento de RNA , Adenosina/análogos & derivados , Proteínas de Ciclo Celular/genética , Feminino , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/genética , Neoplasias Ovarianas/genética , Fatores de Processamento de RNA/genética , Proteínas de Ligação a RNA/genéticaRESUMO
Objective: To describe the surgical techniques and short-term outcomes for 50 cases of modified sacrospinous ligament fixation via the anterior vaginal wall path for pelvic organ prolapse. Methods: 100 patients with pelvic organ prolapse (stage III or stage IV based on POP-Q staging) from January 2018 to January 2020 were retrospectively analyzed. Among them, 50 patients received modified sacrospinous ligament fixation via the anterior vaginal wall path for pelvic organ prolapse (mSSLF group), while the other 50 patients received pelvic reconstruction using T4 mesh (T4 group). Operative time, blood loss, postoperative POP-Q score, length of the hospital stay, complications, and postoperative pain were compared between the two groups. Results: The duration of the operation in mSSLF group was (50 ± 15.2â min), which was shorter than that of the T4 group (60 ± 14.8â min) (p = 0.02). No intraoperative complications were reported from the mSSLF group, whereas one vascular injury occurred in the T4 group. In both groups, postoperative pain and painful intercourse was significantly lower in the mSSLF group than in the SSLF group (p < 0.001). The exposed mesh rate was lower than T4 group. Conclusions: The rates of intraoperative complications, postoperative pain and mesh erosion were significantly lower than those of the T4 group, but there was no significant difference in the efficacy and safety of the treatment of pelvic organ prolapse. So mSSLF may be a feasible technique to manage severe prolapse, with promising short-term efficacy and safety.
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BACKGROUND: Cervical cancer is one of the most prevalent malignancies in gynecology with increasing incidence in recent years. Long noncoding RNAs (lncRNAs) have been reported to regulate human cancers including cervical cancer. F-box and leucine-rich repeat protein 19 antisense RNA 1 (FBXL19-AS1) have been unmasked to exert carcinogenic functions in several cancers except cervical cancer. AIM: Present study hammered at investigating the function and mechanism of FBXL19-AS1 in cervical cancer. METHODS: RT-qPCR was utilized to test gene expression. EdU staining, colony formation, transwell, flow cytometry and TUNEL assays were applied for measuring the impact of FBXL19-AS1 on cervical cancer cell functions. Moreover, RIP, RNA pull-down and luciferase reporter assays were utilized for detecting the correlations among FBXL19-AS1, miR-193a-5p and PIN1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1). RESULTS: FBXL19-AS1 exhibited elevated expression in cervical cancer tissues and cells. Silencing FBXL19-AS1 repressed cell proliferation through arresting cell cycle and stimulating apoptosis, and losing FBXL19-AS1 also restrained cell migration and invasion. Also, we discovered FBXL19-AS1 as a miR-193a-5p sponge, while miR-193a-5p was a tumor inhibitor in cervical cancer. Further, PIN1 was proved as the miR-193a-5p target, and FBXL19-AS1 augmented PIN1 expression in cervical cancer via sequestering miR-193a-5p. Of note, PIN1 accelerated the progression of cervical cancer, and its upregulation counteracted the impacts of depleted FBXL19-AS1 on cervical cancer cell functions. CONCLUSION: FBXL19-AS1 contributes to malignant phenotypes in cervical cancer by sponging miR-193a-5p and regulating PIN1.
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Circular RNAs (circRNAs) are novel non-coding RNAs that have been reported to be involved in the progression of numerous diseases. However, the clinical diagnostic value of circRNAs in female reproductive system diseases remains unknown. The present study is a systemic review and meta-analysis of the available literature on circRNAs as novel biomarkers for female reproductive system diseases. Relevant studies were systematically searched using the PubMed, Embase, Web of Science and Cochrane Library databases. The data obtained from the included studies were analyzed by RevMan5.3 and STATA 14.2. A total of six studies involving 613 individuals across three types of disease examined the diagnostic capabilities of circRNAs. Within these publications, the pooled sensitivity of circRNAs was 0.70 (95% CI, 0.64-0.76), and the pooled specificity was 0.70 (95% CI, 0.64-0.75). The pooled positive likelihood ratio and negative likelihood ratio were 2.33 and 0.42, respectively. The diagnostic score was 1.70 and the pooled diagnostic odds ratio was 5.48. The area under the summary receiver operator characteristic curve was 0.76 (95% CI, 0.72-0.79), indicating that circRNAs exhibited a moderate diagnostic value for female reproductive system diseases and may function as potential diagnostic biomarkers. However, further studies are required to verify the clinical applications of circRNAs.
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BACKGROUND: Increasing evidence has indicated that circular RNAs (circRNAs) play vital roles in modulating tumor progression. However, regulatory roles and underlying mechanisms of circRNA circ_0072995 in epithelial ovarian cancer (EOC) are not well characterized. RESULTS: Circ_0072995 was up regulated in EOC afflicted tissues and cell lines (HO8910 and A2780), and was mainly located in the cytoplasm. The expression of circ_0072995 was associated with the pathological grade of EOC for respective patients. Functional experiments revealed that circ_0072995 promoted EOC cell proliferation, migration, induced apoptosis, as well as enhanced tumorigenesis in vivo. Mechanistic analyses indicated that circ_0072995 may have acted as a sponge of miR-147a such as to relieve repressive effects of miR-147a upon its target CDK6. CONCLUSIONS: Our results revealed that circ_0072995 promoted EOC progression through the circ_0072995/miR-147a/CDK6 axis and may represent a strategy for treatment of EOC afflicted patients. METHODS: Expression of circ_0072995 was evaluated in 40 EOC tissue samples and cell lines by qRT-PCR. The location of circ_0072995 was determined via nuclear-cytoplasmic fractionation. A series of functional experiments facilitated determinations of effects of circ_0072995 on EOC progression in vitro, and in vivo. Underlying mechanisms and influence of circ_0072995 on EOC were confirmed by bioinformatic analyses, luciferase reporter assays, qRT-PCR, and Western blotting.
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PEA15 (Proliferation And Apoptosis Adaptor) is a 15kDa multifunctional phosphoprotein involved in various essential biological processes such as proliferation and apoptosis of cancer cells. Previous studies have demonstrated that PEA15 can promote the progression of many malignancies. In the present study, the expression of PEA15 in ovarian cancer and normal tissues analyzed in several databases and PEA15 was found to be significantly up-regulated in OC tissues compared to normal tissues. Immunochemical assays performed using 171 OC tissue specimens proved that the expression of PEA15 was remarkably positively correlated with the FIGO stage and associated with histologic subgroups of ovarian cancer. IHC assay for the two phosphorylation sites of PEA15 S116 and S104 was also performed. PEA15 high expression predicted a poor prognosis in OC patients analysed from K-M plot dataset. In addition, we proved knockdown of PEA15 inhibits OC cell proliferation and induces cell apoptosis by Bcl2 downregulation and Bax and cleaved Caspase-3 upregulation. Overexpression of PEA15 promotes the proliferative capacity of OC cells. Moreover, this study first discovered PEA15 expression in OC can be negatively regulated by microRNA212. Overexpression of miR-212 in ovarian cancer cells could cause downregulated the expression of PEA15 expression. Overexpression of miR-212 was found to exerted similar effects on the proliferation, and apoptosis of the ovarian cancer cells as that of PEA15 suppression. Additionally, overexpression of PEA15could at least partially abolished the effects of miR-212 on the proliferation, and apoptosis of ovarian cancer cells. In conclusion, our findings revealed PEA15 appears as a novel predictive biomarker, thus providing a valuable therapeutic target in OC treatment strategy.
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INTRODUCTION: Proline hydroxylase 2 (PHD2) is involved in tumorigenesis. This study aimed to examine PHD2 and hypoxia-inducible factor 1α (HIF-1α) expression in different endometrial tissues and explore the correlations between PHD2 and HIF-1α expression with clinicopathological characteristics of endometrial cancer. METHODS: We collected 50 tissue sections of endometrial adenocarcinoma, 30 of atypical endometrial hyperplasia, and 30 of control normal endometrium. The expression of PHD2 was detected by PCR, Western blot, and immunohistochemical analysis. RESULTS: PHD2 mRNA and protein levels reduced in endometrial cancer tissues compared to normal endometrium (p<0.05). In contrast, HIF-1α expression levels increased in endometrial cancer tissues compared to normal endometrium (p<0.05). In addition, PHD2 and HIF-1α levels were correlated with lymphovascular stromal invasion (LVSI), postoperative FIGO stage, and lymph node metastasis of endometrial cancer (p<0.05). CONCLUSION: Our findings suggest that reduced expression of PHD2 and increased expression of HIF-1α are associated with endometrial cancer aggressiveness. PHD2 might be a novel biomarker and a potential target for endometrial cancer management.
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MicroRNAs (miRNAs/miRs) are a class of conserved non-coding endogenous small regulatory RNAs that regulate target gene expression by binding to the 3'-untranslated region of target mRNAs in a base-pairing manner, resulting in repression of transcription or degradation of target mRNAs. It has been demonstrated previously that the abnormal expression of miRNAs is involved in the carcinogenesis and progression of cervical cancer. The aim of the present study was to investigate the expression, biological functions and underlying molecular mechanisms of miR-195 in cervical cancer. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of miR-195 in cervical cancer tissues and cell lines. Following transfection, an MTT assay, cell migration and invasion assays, western blot analysis and a dual-luciferase reporter assay were performed in human cervical cancer cells. In the present study, it was identified that miR-195 was downregulated in cervical cancer tissues and cell lines. Additionally, upregulation of miR-195 and knockdown of hepatoma-derived growth factor (HDGF) inhibited proliferation, migration and invasion of cervical cancer cells. Furthermore, a dual-luciferase reporter assay identified that HDGF was a direct target gene of miR-195. RT-qPCR and western blot analysis demonstrated that miR-195 mimic inhibited HDGF expression at the mRNA and protein levels, whereas miR-195 inhibitor enhanced HDGF expression at the mRNA and protein levels. These results indicated that miR-195 targeted HDGF to inhibit the behavior of tumors in cervical cancer. These results also suggested that miR-195 was a potential therapeutic biomarker of cervical cancer.
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The current standard treatment for ovarian cancer is aggressive surgery followed by platinum-based combination chemotherapy. Recurrence and chemotherapeutic drug resistance are the two main factors that account for the high mortality of most ovarian cancers. Liposomal doxorubicin is primarily used for the treatment of ovarian cancer when the disease has progressed after platinum-based chemotherapy. However, relatively little is known about the genomic changes that contribute to both cisplatin and doxorubicin resistance in high-grade serous ovarian cancer (HGSC) under the selective pressure of chemotherapy. Here, we found that protein tyrosine phosphatase PTPN3 gene expression was substantially increased in both cisplatin and doxorubicin-resistant ovarian cancer cells. Silencing of PTPN3 restored sensitivity to cisplatin and doxorubicin in resistant ovarian cancer cells. Down-regulation of PTPN3 also inhibited cell cycle progression, migration, stemness in vitro and the tumorigenicity of resistant ovarian cancer cells in vivo. Meanwhile, the expression of PTPN3 was found to be regulated by miR-199 in resistant ovarian cancer cells. These findings suggest that PTPN3 promotes tumorigenicity, stemness and drug resistance in ovarian cancer, and thus is a potential therapeutic target for the treatment of ovarian cancer.