LncRNA EWSAT1 通过 miR-330-5p 上调 CPEB4 促进宫颈癌发展。
- 作者列表："Zhou Q","Xie Y","Wang L","Xu T","Gao Y
:Long non-coding RNA (lncRNA) Ewing sarcoma associated transcript 1 (EWSAT1) is an oncogene in a variety of tumors. Here, we planned to demonstrate EWSAT1 function in cervical cancer and further illustrate its underlying mechanism. EWSAT1 expression in cervical cancer was evaluated through qRT-PCR. Colony forming capacity was measured by colony formation assay and cell proliferation ability was measured by CCK-8 kit. Wound healing experiment was applied to test the cell migration and transwell assay was applied to test the invasion ability. Luciferase assay was employed to demonstrate EWSAT1 and miR-330-5p interaction. In cervical cancer, the expression of EWSAT1 was enhanced and contributed to the poor prognosis. Downregulated EWSAT1 expression inhibited Hela cell migration, proliferation, and invasion. EWSAT1 targeted to miR-330-5p and upregulated cytoplasmic polyadenylation element-binding protein 4 (CPEB4) expression by sponging miR-330-5p. Our study revealed that EWSAT1 enhances CPEB4 expression through sponging miR-330-5p, thereby promoting cervical cancer development, which might provide potential therapeutic targets for clinically cervical cancer patients.
: 长链非编码 RNA (lncRNA) 尤文肉瘤相关转录本 1 (EWSAT1) 是多种肿瘤中的癌基因。在此，我们拟证明 EWSAT1 在宫颈癌中的功能，并进一步阐明其潜在机制。通过 qRT-PCR 评价 EWSAT1 在宫颈癌中的表达。用集落形成法测定集落形成能力，用 CCK-8 试剂盒测定细胞增殖能力。创面愈合实验检测细胞迁移，transwell 实验检测细胞侵袭能力。荧光素酶测定用于证明 EWSAT1 和 miR-330-5p 相互作用。在宫颈癌中，EWSAT1 的表达增强，并有助于不良预后。下调 EWSAT1 表达抑制 Hela 细胞迁移、增殖和侵袭。EWSAT1 靶向 miR-330-5p，通过海绵 miR-330-5p 上调细胞质多聚腺苷酸化元件结合蛋白 4 (CPEB4) 的表达。我们的研究揭示 EWSAT1 通过海绵 miR-330-5p 增强 CPEB4 的表达，从而促进宫颈癌的发展，这可能为临床宫颈癌患者提供潜在的治疗靶点。
METHODS:STUDY OBJECTIVE:To evaluate the differences in perioperative outcomes and immediate complication rates between laparoscopic myomectomy for submucous myomas and laparoscopic myomectomy for myomas in other locations. DESIGN:Retrospective cohort study. SETTING:University-affiliated hospital in London. PATIENTS:A total of 350 patients with symptomatic uterine myomas underwent laparoscopic myomectomy. Thirty-three of these were performed for submucous myomas (group 1), and 317 were for myomas in other uterine locations (group 2). INTERVENTIONS:Analysis of prospectively collected data on patient demographics, myoma characteristics, perioperative outcomes, and immediate complications. MEASUREMENTS AND MAIN RESULTS:Patient demographics, including age, body mass index, and parity, were similar in the 2 groups. No significant differences in myoma characteristics were seen between groups 1 and 2, including the mean dimension of largest myoma (7.1 vs 7.8 cm, respectively; p = .35), mean number of myomas removed (3.8 vs 4.1; p = .665), and mean mass of myomas removed (142.0 g vs 227.3 g; p = .186). There were also no significant between-group differences in any perioperative outcomes, including mean blood loss (226.8 mL vs 266.4 mL; p = .373), duration of surgery (103 minutes vs 113 minutes; p = .264), and duration of hospital stay (1.4 days vs 1.7 days; p = .057). No complications arose from laparoscopic resection of submucous myomas. CONCLUSION:Laparoscopic myomectomy for submucous myomas has similar perioperative outcomes and immediate complications as laparoscopic myomectomy for other myomas and can be considered for large or type 2 submucous myomas.
METHODS:INTRODUCTION:Laparoscopic myomectomy can be difficult when fibroids are large and numerous. This may result in extensive intraoperative bleeding and the need for a conversion to a laparotomy. Medical pretreatment prior to surgery might reduce these risks by decreasing fibroid size and vascularization of the fibroid. We compared pretreatment with ulipristal acetate (UPA) vs gonadotropin-releasing hormone agonists (GnRHa) prior to laparoscopic myomectomy on several intra- and postoperative outcomes. MATERIAL AND METHODS:We performed a non-inferiority double-blind randomized controlled trial in nine hospitals in the Netherlands. Women were randomized between daily oral UPA for 12 weeks and single placebo injection or single intramuscular injection with leuprolide acetate and daily placebo tablets for 12 weeks. The primary outcome was intraoperative blood loss. Secondary outcomes were reduction of fibroid volume, suturing time, total surgery time and surgical ease. RESULTS:Thirty women received UPA and 25 women leuprolide acetate. Non-inferiority of UPA regarding intraoperative blood loss was not demonstrated. When pretreated with UPA, median intraoperative blood loss was statistically significantly higher (525 mL [348-1025] vs 280 mL[100-500]; P = 0.011) and suturing time of the first fibroid was statistically significantly longer (40 minutes [28-48] vs 22 minutes [14-33]; P = 0.003) compared with GnRHa. Pretreatment with UPA showed smaller reduction in fibroid volume preoperatively compared with GnRHa (-7.2% [-35.5 to 54.1] vs -38.4% [-71.5 to -19.3]; P = 0.001). Laparoscopic myomectomies in women pretreated with UPA were subjectively judged more difficult than in women pretreated with GnRHa. CONCLUSIONS:Non-inferiority of UPA in terms of intraoperative blood loss could not be established, possibly due to the preliminary termination of the study. Pretreatment with GnRHa was more favorable than UPA in terms of fibroid volume reduction, intraoperative blood loss, hemoglobin drop directly postoperatively, suturing time of the first fibroid and several subjective surgical ease parameters.
METHODS:AIMS:Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH-negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance. METHODS AND RESULTS:We evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)-based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH-negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil-like cytoplasm. We found that six (86%) of seven FH-negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours. CONCLUSION:Our study showed a relatively high rate of FH germline mutation in FH-negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.