Backgroud Persistent infection with high-risk human papillomavirus type 16 (HPV16) is a principal etiological factor in cervical cancer. Nevertheless, the molecular events linking HPV16-associated lesion progression to malignant transformation remain insufficiently characterized, particularly those involving vesicular trafficking and autophagy regulation.Methods Proteomic analysis was conducted across five stages of HPV16-associated cervical lesion progression to identify differentially expressed proteins. The expression of vesicle-associated membrane protein 7 (VAMP7) was validated in cervical tissue specimens and cellular models. Gain- and loss-of-function approaches were employed to assess the effects of VAMP7 on cellular proliferation, migration, invasion, and apoptosis. Autophagic activity was evaluated by LC3 lipidation, autophagosome accumulation, and analysis of SNARE complexrelated proteins. The in vivo effects of VAMP7 were examined using xenograft tumor models.Results VAMP7 demonstrated dynamic expression changes during cervical lesion progression, characterized by decreased expression in HPV16-positive non-malignant tissues and a gradual increase with disease severity, reaching the highest levels in advanced cervical cancer. Functionally, VAMP7 enhanced proliferation, migration, and invasion while inhibiting apoptosis in cervical cancer cells, whereas distinct effects were observed in non-tumor cervical epithelial cells. Mechanistically, VAMP7 regulated autophagic flux through modulation of SNARE-mediated vesicle fusion, resulting in altered autophagosome accumulation and autophagy-related signaling. In xenograft models, VAMP7 overexpression significantly promoted tumor growth and increased the expression of autophagy-associated markers.Conclusion These data indicate that dysregulation of VAMP7-mediated autophagy contributes to cervical carcinogenesis in an HPV16-associated context. VAMP7 may represent a potential therapeutic target for the treatment of cervical cancer.Key points VAMP7 displays dynamic expression changes during HPV16-associated cervical lesion progression. VAMP7 promotes malignant phenotypes of cervical cancer cells by regulating autophagic flux via SNARE-mediated vesicle fusion. Dysregulated VAMP7-mediated autophagy contributes to cervical carcinogenesis in an HPV16-associated context.

e17531 Background: Persistent infection with high-risk human papillomavirus(HR-HPV), particularly HPV16, is a major risk factor for the development of cervical intraepithelial neoplasia (CIN), which can progress through various stages and eventually lead to cervical cancer. Traditional in vitro models often fail to capture the complex immune interactions that occur within tissue. To address this limitation and better understand HPV-associated cervical lesion progression, we have developed patient-derived organoids that represent five distinct stages, from early CIN to cervical cancer. Methods: These organoids were derived from various stages of HPV infection: HPV-negative & Normal tissue, HPV16-positive & Normal tissue, HPV16-positive & LSIL, HPV16-positive & HSIL, and HPV16-positive & CA. Cervical tissue specimens were soaked in a washing solution for 3 minutes, followed by three washes in a 50 mL tube with 5 mL of solution each time. Cleaned tissue blocks were cut into 1 mm³ microtissue blocks and placed in a 10 cm culture dish with 100–200 μL of culture medium. The blocks were then resuspended in 1 mL of medium and transferred to a new dish with 15 mL of medium. The medium was partially refreshed every 5–7 days to maintain organoid growth. Organoid growth was monitored, and transcriptome sequencing was performed to analyze gene expression profiles. Whole-exome sequencing (WES) and single-cell RNA sequencing were used to assess genetic variations and immune cell compositions. HE staining was employed to evaluate histological characteristics. Results: The primary culture of cervical organoids resulted in the formation of three-dimensional spherical structures with organoid-like characteristics. HE staining of the organoids showed structural similarities to the source tissue. Whole-exome sequencing (WES) of organoids derived from HPV16-negative normal tissue, HPV16-positive&HSIL, and HPV16-positive&CA showed high mutation overlap rates, indicating that the organoids maintain a high degree of similarity to the tissue in terms of mutation profiles. This indicates that the organoid culture system preserves most of the tissue-originated mutations. Single-cell RNA sequencing analysis of organoids from HPV16-positive normal tissue and HPV16-positive cancerous tissue showed that the organoids effectively retain the immune microenvironment of the source tissue. Conclusions: This study demonstrates the successful construction of cervical organoids representing five distinct stages of cervical lesions, each with a preserved native immune microenvironment. These organoids provide a more physiologically relevant model for investigating HPV infection and immune responses at different stages of disease progression.

Background:Given the excellent prognosis of early-stage cervical cancer, fertility-sparing surgery has grown as a priority, significant alternative for radical hysterectomy in women being of reproductive age. We aimed to investigate the outcomes and subsequent pregnancies of early-stage cervical cancer patients who received radical trachelectomy. Moreover, there is a scarcity of literature directly comparing the impact of whether performing cervical cerclage concurrently with radical trachelectomy on patients' reproductive outcomes. Methods:Women with IA1-IB2 cervical cancer who underwent fertility-sparing surgery at the Obstetrics and Gynecology Hospital of Fudan University were reviewed from January 2014 to May 2024.Radical trachelectomy in 70 women was performed by surgical team from the gynecologic oncologic center. Clinical characteristics, intraoperative, pathological results, oncologic, fertility and follow-up data of these patients were recorded and retrospectively analyzed. This study compared surgical and perinatal outcomes between patients who underwent cervical cerclage during radical trachelectomy (n=49) and those who did not receive the procedure simultaneously (n=21). Results:A total of 70 women (mean age: 31years) underwent radical trachelectomy (RT) of whom 68.6% were nulliparous. The FIGO stage distribution was IA1 (n=6), stage IA2 (n=7), stage IB1 (n=49), and stage IB2 (n=8). The operative duration was significantly longer in the cerclage group than in the control group (285.4±63.9 min vs 204.8±61.9 min; p < 0.001, 95% CI 47.51-113.48) with greater intraoperative blood loss (201.0 mL vs 170.1 mL, p=0.187, 95% CI -15.10-75.72). Overall, 36 women (51.4%) were seeking parenthood, and 26 succeeded (72.2%). There were 20 live births (76.9%), 12 women delivered in term (46.2%), 7 infants were born between 32 and 36+6 weeks, 1 between 28 and 31+6 weeks, all live birth. The mean neonatal birth weight was slightly lower in the cerclage group than in the control group (2625 g vs 2828.6 g; p=0.265, 95% CI -575.17 to 168.03). At the end of the follow-up period (median 68.7 months, range 34-153 months), one individual is currently 27+3 weeks pregnant, three patient had recurrence, and all women are alive and 20 children born to fertility-sparing surgery patients exhibited normal development. Conclusion:Radical trachelectomy provides excellent oncologic results with an outstanding fertility rate and obstetric outcome for patients with early cervical cancer. RT combined with intrauterine-cervical stent is a safe and effective fertility-sparing surgery but cervical cerclage is not recommended.

BACKGROUND:Cervical cancer, prevalent in low- and middle-income countries, is primarily caused by high-risk HPV16. Vesicle-Associated Membrane Protein 8 (VAMP8), involved in vesicle trafficking and autophagy, may influence HPV16-related cervical cancer progression. METHODS:VAMP8 expression was evaluated in cervical tissue specimens from patients with HPV16-positive lesions (including low- and high-grade squamous intraepithelial lesions and cancer) and HPV-negative normal controls using proteomics, qPCR, and immunohistochemistry. A Cox proportional hazards model for prognosis was developed using immunohistochemical data from a cohort of cervical cancer patients. The clinical significance of VAMP8 was further assessed using RNA-seq and clinical data from The Cancer Genome Atlas-Cervical Cancer (TCGA-CESC) cohort. The effects of VAMP8 on autophagy and tumor progression were examined in HPV16 E6/E7-immortalized cervical epithelial cells (Ect1/E6E7) and cervical cancer cell lines (SiHa, HeLa, C-33A) in vitro, and in a SiHa xenograft model in vivo. Transcriptomic analysis of Ect1/E6E7 and SiHa cells identified VAMP8-regulated pathways. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays in SiHa cells were used to confirm the regulation of the HIF-1 pathway. RESULTS:VAMP8 was upregulated in HPV16-positive samples, particularly in low-grade squamous intraepithelial lesions (LSIL). Elevated VAMP8 correlated with poor survival outcomes and advanced tumor stages. VAMP8 enhanced autophagy and reduced proliferation and invasiveness in HPV16-positive cervical cells but increased in established cancer cell lines. In vivo, VAMP8 overexpression promoted tumor growth and autophagy. The HIF-1 pathway emerged as a key regulatory axis of VAMP8, enhancing hypoxic responses and angiogenesis. CONCLUSION:Elevated VAMP8 in HPV16-associated cervical cancer promotes tumor progression by enhancing autophagy via the HIF-1 pathway, suggesting its potential as a diagnostic and prognostic biomarker.

Objective: The objective of this study was to identify the risk factors for postoperative pathological escalation of endometrial cancer in patients with a pathologic diagnosis of endometrial intraepithelial neoplasia (EIN) before surgery. Some of the clues from the preoperative assessment were used to build a nomogram to predict the likely pathological escalation after surgery, and to explore the feasibility of sentinel lymph node biopsy in these patients with possible pathological escalation. Methods: This was a retrospective analysis of patients who underwent surgical treatment for EIN diagnosed before surgery between 2018 and 2023 in The Obstetrics and Gynecology Hospital of Fudan University. parameters including clinical, radiological and histopathological factors were analyzed by univariate and multivariate logistic regression to determine the correlation with pathology upstaging. A nomogram based on the multivariate results was developed to predict the probability of pathology upstaging. A total of 729 patients were included, divided into training set and validation set. 484 patients were used to build the model. This nomogram was subsequently validated using 245 patients. Results: Upstaging to endometrial carcinoma occurred in 115 (23.8 percent) of 484 women treated between 2018 and 2023 in training set. A lager endometrial thickness (at least 15 mm), menopause, hypertension, HE4, and endometrial blood were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic curve (AUC)=0.6808; 95% confidence interval [CI]=0.6246-0.7369). The nomogram showed similar predictive performance in the validation data set, based on another 245 women (AUC=0.7821; 95% CI=0.7076-0.8567). Conclusion: This study developed a novel nomogram based on the 5 most important factors, which can accurately predict invasive cancer. It is common for women with preoperative diagnosis of EIN to experience pathological progression to endometrial cancer. For some patients with postoperative pathological escalation, we found lymph node metastasis. This nomogram may be useful to help doctor decide whether to perform sentinel lymph node biopsy for surgical staging in these EIN patients. According to the nomogram, simultaneous sentinel lymph node biopsy in patients with high probability of postoperative pathological upgrading can provide better guidance for postoperative adjuvant treatment of endometrial cancer and avoid the occurrence of secondary surgery.

BACKGROUND:Several risk factors have been identified that compromise the treatment outcome in patients with early-to-mid-stage cervical cancer (CC) who are primarily treated with radical surgery. However, there is no report on the impact of intraoperative frozen pathology examination of vaginal margins on the prognosis of patients with CC. This study aimed to conduct a randomized controlled trial (RCT) to determine whether selective vaginal resection can reduce the incidence of operative complications and the risk of postoperative radiotherapy. The impact of the length of the vagina removed in radical hysterectomy (RH) on prognosis and quality of life (QoL) for IB2-IIA2 CC patients will be investigated. METHODS:A multicenter, non-inferiority, RCT at 7 institutions in China is designed to investigate the effect of intraoperative frozen pathology exam of vaginal margin in RH on the survival outcomes for patients with IB2-IIA2 CC. Eligible patients aged 18-70 years will be randomly assigned online by one-to-one random allocation to receive intraoperative frozen pathology exam of vaginal margin or not. If frozen pathology indicates positive margin, continue resection of 1 centimeter of vaginal tissue until negative margin is achieved. The primary end point is 2-year disease-free survival (DFS). Adverse events (AEs) caused by further vagina resection, 5-year DFS, 2-year overall survival (OS), 5-year OS and AEs caused by radiotherapy and QoL are secondary end points. A total of 310 patients will be enrolled from 7 tertiary hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION:Chinese Clinical Trial Registry Identifier: ChiCTR2000035668.

Long non-coding RNAs (lncRNAs) represent a class of versatile molecules that exhibit the potential to regulate gene expression at various levels, namely transcriptional, post-transcriptional and epigenetic, thereby influencing critical cellular processes such as proliferation, apoptosis, invasion and drug resistance. The lncRNA H19, among the earliest identified within this category, has emerged as a significant participant in the pathogenesis of a multitude of both malignant and benign gynecological diseases. An escalating body of evidence indicates a functionally pertinent network of lncRNA H19 coexpression linked with the extracellular matrix architecture and immune microenvironment during cancer progression. This association may provide insightful leads for the selection of innovative diagnostic biomarkers and assist in the delineation of potent pharmaceutical targets for gynecological oncology. The present comprehensive review presented a synthesis of the expression profiles and multifaceted implications of lncRNA H19 across a spectrum of gynecological pathologies.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disease characterized by excessive fat accumulation, and is the major risk for cardiovascular and metabolic disorders. We explored the therapeutic effect of gypenosides (Gyps) in combination with capsaicinoids (Caps) against high-fat-diet (HFD)-induced rat hyperlipidemia and oxidized low-density lipoprotein (ox-LDL)-treated Raw264.7 cells. Network pharmacology analysis predicted that the potential molecular mechanism of Gyps/Caps combination against hyperlipidemia was mainly associated with steroid metabolism, lipid synthesis and inflammatory response. Animal experiment demonstrated that Gyps/Caps combination lowered the liver weight, liver index, serum lipid profile and hepatic cholesterol content, improved liver function by reducing the serum markers of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), thereby relieving the hepatic injury. Moreover, Gyps/Caps combination inhibited oxidative stress by decreasing the lactic dehydrogenase (LDH) activity and increasing the superoxide dismutase (SOD) activity. Western blotting result suggested that Gyps/Caps combination could upregulate the expressions of peroxisome proliferator-activated receptors ? (PPAR?), liver X receptor a (LXRa), ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) in the liver tissue. Cellular experiment revealed that the combination treatment protected RAW264.7 cells from ox-LDL induction through inhibiting apoptosis, lipid-decreasing and anti-inflammation, and caused the dramatic enhancement on PPAR? expression. Notably, the combined use of Gyps and Caps did not influence the pharmacological outcomes of each other, but significantly enhanced the overall therapeutic effect in ameliorating HFD-induced hyperlipidemia. Our research provided an experimental basis for advanced research and clinical application of Gyps/Caps combination. Importantly, our cumulative data indicated that combination use of Gyps and Caps may be an effective therapeutic strategy for alleviating hyperlipidemia-induced NAFLD.

Macrophages are the origin of most foam cells in the early stage of atherosclerotic plaques. However, the mechanism involved in the formation of macrophage-derived foam cell formation remains unclear. Here, we revealed that the hedgehog (Hh) signaling is critical in autophagy-lysosome pathway regulation and macrophage-derived foam cell formation. Inhibition of Hh signaling by vismodegib ameliorated lipid deposition and oxidative stress level in atherosclerotic plaques in high-fat diet-fed apoE−/− mice. For mechanistic study, how the Hh signaling modulate the process of foam cell formation were accessed afterward. Unexpectedly, we found that suppression of Hh signaling in apoE−/− mice had no significant impact on circulating cholesterol levels, indicating that Hh pathway modulate the procession of atherosclerotic plaque not through a traditional lipid-lowing mechanism. Instead, vismodegib was found to accelerate autophagosomes maturation as well as cholesterol efflux in macrophage-derived foam cell and in turn improve foam cell formation, while autophagy inhibitors (LY294002 or CQ) administration significantly attenuated vismodegib-induced cholesterol efflux and reversed the effect on foam cell formation. Therefore, our result demonstrated that inhibition of the Hh signaling pathway increases cholesterol efflux and ameliorates macrophage-derived foam cell formation by promoting autophagy in vitro. Our data thus suggested a novel therapeutic target of atherosclerosis and indicated the potential of vismodegib to treat atherosclerosis.

Introduction/Background Human papillomavirus type 16 (HPV16) is a central carcinogenic factor in cervical cancer.VAMP8 (vesicle-associated membrane protein 8) is a membrane-bound protein involved in intracellular vesicle transport and fusion processes, regulating various biological activities. This study aims to investigate the expression and biological function of VAMP8 in cervical disease progression. Methodology Proteomics analysis was employed to study the relative expression of VAMP8 in cervical cell lines (ECT-1, Hela, SiHa, C-33). TCGA was used to explore the cancer prognosis and immune infiltration.CCK-8, Transwell, and flow cytometry techniques were employed to analyze the effects of VAMP8 on cell proliferation, migration, invasion,cell cycle distribution, and apoptosis. Transmission electron microscopy, immunofluorescence, and WB experiments were conducted to detect autophagy levels. Tumor growth and metastasis in vivo was evaluated using a nude mouse subcutaneous xenograft model. Results Proteomics analysis revealed that VAMP8 expression was higher in LSIL than HSIL and cervical cancer but significantly higher than in normal HPV16-negative cervical tissues. In vitro experiments demonstrated that relative overexpression of VAMP8 in HPV16-positive ECT-1 cells resulted in increased autophagic flux, decreased cell proliferation, migration, invasion, increased apoptosis, and an increased proportion of cells in the G1 phase. In other words, elevated VAMP8 expression in HPV16-infected cervical cells promotes autophagy while inhibiting normal cervical cell growth. In cervical cancer cells, high VAMP8 expression promotes autophagy and tumor cell growth. In vivo experiments further confirmed that overexpression of VAMP8 promotes cervical cancer growth and metastasis. Conclusion VAMP8 promotes autophagy in cervical cells, inhibiting cellular function and maintaining homeostasis in the early stages of persistent HPV16 infection. However, in cervical cancer, VAMP8 promotes tumor cell growth and metastasis. This may be due to the differing roles of autophagy at various stages of tumor development. These findings suggest that VAMP8 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer. Disclosures The work was supported by National Natural Science Foundation of China (No. 82001500).

The aim of this study was to develop and internally validate a nomogram of the probability EC patients surviving longer than 5 years. Quantitative real-time PCR (qRT–PCR) was implemented to analyze the expression of lncRNA-LA16c-313D11.11 in 60 EC tissues. The clinicopathological characteristics and follow-up data were retrospectively gathered and analyzed. To establish the prediction model, multivariate logistic regression analysis was applied, and the discrimination, calibration, and clinical practicability of the prediction model were assessed with a concordance index (C-index), calibration chart, and decision curve analysis. Bootstrap validation was performed for internal validation. The prediction factors included the age of patients, myometrial invasion, lymphovascular space invasion, histological subtype, and the expression of lncRNA-LA16C-313D11.11. The model demonstrated good calibration and modest discrimination (C-index = 0.860, 95

The long noncoding RNA (lncRNA) H19 is involved in the pathogenesis of endometriosis by modulating the proliferation and invasion of ectopic endometrial cells in vitro, but related in vivo studies are rare. This study aimed to investigate the role of lncRNA H19 in a nude mouse model of endometriosis. Ectopic endometrial stromal cells (ecESCs) were isolated from ectopic endometrium of patients with endometriosis and infected with lentiviruses expressing short hairpin RNA (shRNA) negative control (LV-NC-shRNA) or lncRNA-H19 shRNA (LV-H19-shRNA). The ecESCs infected with LV-NC-shRNA and LV-H19-shRNA were subcutaneously implanted into forty 6- to 8-week-old female nude mice. The size and weight of the endometriotic implants were measured at 1, 2, 3, and 4 weeks after implantation and compared, and lncRNA H19 levels in endometriotic implants were evaluated using real-time polymerase chain reaction (RT-PCR). All nude mice survived the experimental period, and no significant differences in body weight were observed between the experimental group and the control group. All nude mice developed histologically confirmed subcutaneous endometriotic lesions with glandular structures and stroma after 1 week of implantation. The subcutaneous lesions in the LV-NC-shRNA group after 1, 2, 3, and 4 weeks of implantation were larger than those in the LV-H19-shRNA group, and lncRNA H19 levels in subcutaneous lesions in the LV-NC-shRNA group were significantly higher than those in the LV-H19-shRNA group. Knockdown of lncRNA H19 suppresses endometriosis in vivo. Further study is required to explore the underlying mechanism in the future.

Objective:The research paid close attention to the function of lncRNA-related endogenous competitive RNAs (ceRNAs) network in endometrial cancer (EC).Methods: 45 primary endometrial cancer tissues (EC) and 45 normal endometrium (NE) were included in the research.The online software StarbaseV2.0 was made use of forecasting the lncRNA which most likely contained microRNA-200c-3p combining sites and could interact with microRNA-200c-3p.Subsequently, we chose lncRNAs which were consistent with the characteristics of polyadenylation of lncRNAs and lower expression in EC than that of NE.After that, lncRNAs, which were related with the microRNA-200c-3p-noxa network, were identified.Results: Rp11-379k17.4,a new gene related to endometrial cancer, was identified as noncoding RNA.It was a more effective ceRNA associated with the microRNA-200c-3p-noxa network.Conclusion: LncRNAs possess microRNA response elements (MREs) and give scope to significant roles in the post-transcriptional mechanism in EC.

目的 通过检测子宫内膜癌组织中长链非编码RNA(lncRNA)-LA16c-313D11.11和突变型 p53的表达以探讨其与子宫内膜癌发生、发展之间的关系.方法 收集复旦大学附属妇产科医院2013年9月—2016年9月收治的54例子宫内膜癌患者的临床资料.采用实时荧光定量PCR和免疫组织化学染色法,分别检测lncRNA-LA16c-313D11.11和突变型p53的表达.以lncRNA-LA16c-313D11.11相对表达量的中位数(1.168)为标准,将患者分为低表达组(≤1.168)与高表达组(＞1.168).对患者lncRNA-LA16c-313D11.11和突变型p53的表达情况与临床和病理学特征进行相关性分析.结果 lncRNA-LA16c-313D11.11高表达组和低表达组患者在国际妇产科联盟(FIGO)分期Ⅰ期、Ⅱ期、Ⅲ或Ⅳ期患者中的占比分别为66.67％和33.33％、4/7和3/7、3/11和8/11,差异有统计学意义(P＜0.05).高表达组和低表达组在发生淋巴结转移患者中的占比分别为3/11和8/11,在未发生淋巴结转移患者中的占比分别为65.12％和34.88％,差异有统计学意义(P＜0.05).突变型p53阳性患者在子宫内膜样腺癌、浆液性腺癌和透明细胞癌患者中的占比分别为19.51％、7/9、2/4,在无和有淋巴转移患者中的占比分别为23.26％、7/11,差异均有统计学意义(P值均＜0.05).高表达组和低表达组突变型p53阳性的患者占比分别为6/7和11/17,差异有统计学意义(P＜0.05).结论 lncRNA-LA16c-313D11.11的高表达与子宫内膜癌分期早、无淋巴结转移相关,lncRNA-LA16c-313d11.11可能通过p53在子宫内膜癌的调控中发挥重要作用.

目的 探讨子宫内膜癌(endometrial carcinoma,EC)患者肿瘤组织中长链非编码RNA(long noncoding RNA,lncRNA)RP11-395G23.3的表达水平及其临床意义.方法 选取2013年8月-2016年5月复旦大学附属妇产科医院收治的41例子宫内膜癌患者的病理标本并另选26例正常子宫内膜组织标本作为对照组.采用定量RT-PCR的方法检测RP11-395G23.3在EC组织及正常组织中的表达水平,并分析其表达水平与EC临床病理特征以及免疫组化学指标之间的关系.结果EC患者肿瘤组织中RP11-395G23.3表达水平较对照组显著降低,差异有统计学意义(P＜0.05).RP11-395G23.3表达水平与EC患者的年龄、组织病理分类、绝经情况、FIGO分期、组织学分级、肌层浸润、淋巴结转移、ER、PR及p53表达水平等均无关(P＞0.05).其表达水平与脉管内癌栓形成以及Ki-67水平差异存在统计学意义(x2=4.281,P=0.039;x2=12.060,P=0.002),且RP11-395G23.3与Ki-67表达水平呈负相关(r=-0.379,P=0.014).结论RP11-395G23.3表达水平与子宫内膜癌组织中的Ki-67表达水平及脉管内癌栓形成密切相关.当脉管内见癌栓或Ki-67高表达时,RP11-395G23.3表达水平降低.RP11-395G23.3有望成为辅助子宫内膜癌诊断及预后的生物标志物.

The aim of the present study was to determine the competitive endogenous RNA (ceRNA) network associated with long‑coding RNA (lncRNA) LA16c‑313D11.11 in endometrial cancer (EC). Initially, the expression levels of LA16c‑313D11.11 in 60 EC tissues, 20 atypical hyperplasia endometrium (EAH) tissues and 20 normal endometrium tissues was determined. MicroRNA (miRNA/miR)‑205‑5p mimics and LA16c‑313D11.11 mimics were transfected into HEC‑1A and Ishikawa cells. The expression levels of miR‑205‑5p, LA16c‑313D11.11 and their target proteins were assessed using reverse transcription‑quantitative PCR or western blot analysis. Flow cytometry, Cell Counting kit‑8 assays, Transwell migration assays and wound healing assays were performed to assess the effects of LA16c‑313D11.11 and miR‑205‑5p on the migration and proliferation of tumor cells in vitro. The expression levels of LA16c‑313D11.11 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in human EAH and EC tissues were significantly decreased, whereas the expression levels of miR‑205‑5p in EAH and EC tissues were significantly increased, compared with the normal endometrium tissues. The expression of LA16c‑313D11.11 in human EC tissues negatively correlated with the expression of miR‑205‑5p. Additionally, the overexpression of LA16c‑313D11.11 significantly reduced the invasion, migration and viability of HEC‑1A and Ishikawa cells in vitro. LA16c‑313D11.11 was shown to regulate the expression of PTEN, and the invasion, migration and viability of HEC‑1A and Ishikawa cells, through its microRNA response element to compete for microRNA‑205‑5p. LA16c‑313D11.11 was also shown to modulate the PI3K/AKT signaling pathway. Therefore, LA16c‑313D11.11 acts as an effective ceRNA associated with a microRNA‑205‑5p‑PTEN axis. LA16c‑313D11.11 may inhibit the development and progression of EC by acting as a sponge of miR‑205‑5p, thus indirectly increasing the expression of PTEN.

The focal point of this research was the functional role of RP11-395G23.3 in endometrial cancer (EC). The expression of RP11-395G23.3, microRNA (miRNA)-205-5p, and their target proteins were detected by quantitative real-time polymerase chain reaction and western-blot analyses. Flow cytometry and proliferation, Transwell, and wound healing assays were used to detect the effects of RP11-395G23.3 and miRNA-205-5p on tumor cell migration and proliferation in vitro. RP11-395G23.3 expression was negatively related to miRNA-205-5p, but positively related to phosphatase and tensin homolog (PTEN) expression in human EC tissues. We discovered that low RP11-395G23.3 expression was significantly related to advanced histological grade and lymphovascular space invasion in EC patients. In addition, overexpression of RP11-395G23.3 significantly inhibited the proliferation, invasion, migration, and induced apoptosis of Ishikawa and HEC-1A cells in vitro. Our results also showed that RP11-395G23.3 could directly bind to miRNA-205-5p through its miRNA response elements and eliminate the inhibitory effect of targeting gene PTEN, thus leading to the signaling pathway of phosphatidylinositol-3-kinase/AKT inactivation. We demonstrated for the first time that RP11-395G23.3 may inhibit the development and pathogenesis of EC by acting as a sponge for miRNA-205-5p and increasing PTEN expression. RP11-395G23.3 may be a target for the diagnosis and treatment of EC.

Endometriosis has a high recurrence rate after treatment, and there are no effective recurrence predictors. LncRNA H19 has been found to be a predictor of the poor prognosis of multiple diseases. Here, we aimed to investigate the expression and clinical implications of lncRNAH19 in endometriosis and explore the clinical application value of lncRNAH19 for recurrence prediction. LncRNA H19 expression was evaluated in 104 ectopic and eutopic endometrial samples from patients with endometriosis and 50 control endometrial samples from patients without endometriosis. The association between lncRNA H19 expression and the clinical characteristics of endometriosis as well as its value as a potential predictor of recurrence were analyzed. LncRNA H19 expression in the ectopic and eutopic endometria of endometriosis patients was significantly higher than that in the normal endometrium. LncRNA H19 expression in the ectopic endometrium was associated with infertility, recurrence, bilateral ovarian lesions, an increased CA125 level, and revised American Fertility Society (rAFS) stage. Multivariate logistic regression analysis showed that age less than 40 years and lncRNA H19 overexpression in the ectopic endometrium were independent prognostic factors of endometriosis recurrence, and the receiver operating characteristic (ROC) curve showed that the sensitivity and specificity for predicting recurrence were 90.9% and 61.0%, respectively, when the lncRNA H19 expression level in the ectopic endometrium was higher than 0.0277. LncRNA H19 may be involved in the pathogenesis of endometriosis especially in the mechanism of recurrence and is a novel potential predictor of the recurrence of endometriosis.