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lncRNA DLEU2/miR-455-3p/OTUD7B轴通过PI3K/AKT信号通路促进宫颈癌恶性发展
引用本文:冯钰玲1,顾燕楠1,凌剑梅1,丁易钤2. lncRNA DLEU2/miR-455-3p/OTUD7B轴通过PI3K/AKT信号通路促进宫颈癌恶性发展[J]. 现代肿瘤医学, 2023, 0(14): 2614-2623. DOI: 10.3969/j.issn.1672-4992.2023.14.009
作者姓名:冯钰玲1  顾燕楠1  凌剑梅1  丁易钤2
作者单位:1.南通市妇幼保健院妇产科;2.妇科,江苏 南通 226000
基金项目:南通市卫生健康委员会科研课题青年项目(编号:QA2021046)
摘    要:目的:探讨长链非编码RNA DLEU2(lncRNA DLEU2,DLEU2)对宫颈癌恶性发展的影响。方法:利用TCGA数据库和qRT-PCR分析DLEU2在宫颈癌组织和细胞系中的表达。采用CCK-8、Western blotting、免疫荧光、细胞划痕、Transwell和TUNEL实验检测干扰DLEU2(sh-DLEU2)对宫颈癌细胞增殖、迁移、侵袭和凋亡的影响。生物信息学和双荧光素酶报告基因实验分析DLEU2和miR-455-3p的靶基因,评估miR-455-3p inhibitor/mimic对宫颈癌细胞生长和PI3K/AKT信号通路的影响。裸鼠荷瘤实验检测干扰DLEU2后对瘤体体内生长的影响。结果:宫颈癌组织和细胞系中DLEU2表达显著上调(P<0.01)。sh-DLEU2可抑制Hela和SiHa细胞的增殖、迁移和侵袭(P<0.01),促进细胞凋亡(P<0.001)。DLEU2与miR-455-3p相结合,OTUD7B为miR-455-3p的靶基因。miR-455-3p inhibitor促进细胞恶性发展并激活PI3K/AKT信号通路,而sh-DLEU2可逆转其作用(P<0.01);miR-455-3p mimic也可部分逆转Oe-OTUD7B对细胞的作用(P<0.01)。此外,sh-DLEU2抑制了裸鼠荷瘤组织的生长(P<0.01)。结论:DLEU2通过miR-455-3p/OTUD7B轴激活PI3K/AKT信号通路促进宫颈癌的恶性发展。

关 键 词:宫颈癌  DLEU2  miR-455-3p  OTUD7B  PI3K/AKT信号通路

lncRNA DLEU2/miR-455-3p/OTUD7B axis promotes the malignant progression of cervical carcinoma by regulating PI3K/AKT signaling pathway
FENG Yuling1,GU Yannan1,LING Jianmei1,DING Yiqian2. lncRNA DLEU2/miR-455-3p/OTUD7B axis promotes the malignant progression of cervical carcinoma by regulating PI3K/AKT signaling pathway[J]. Journal of Modern Oncology, 2023, 0(14): 2614-2623. DOI: 10.3969/j.issn.1672-4992.2023.14.009
Authors:FENG Yuling1  GU Yannan1  LING Jianmei1  DING Yiqian2
Affiliation:1.Department of Obstetrics and Gynecology;2.Department of Gynecology,Nantong Maternal and Child Health Hospital,Jiangsu Nantong 226000,China.
Abstract:Objective:To investigate the effects of long non-coding RNA DLEU2 (lncRNA DLEU2,DLEU2) on the malignant progression of cervical carcinoma.Methods:TCGA database and qRT-PCR were used to analyze DLEU2 expression in cervical carcinoma tissues and cell lines.The effects of shRNA-DLEU2 (sh-DLEU2) on cell proliferation,migration,invasion,and apoptosis of cervical carcinoma were assessed using CCK-8,Western blotting,immunofluorescence,wound healing,Transwell,and TUNEL assays.Bioinformatics and dual-luciferase reporter assays were conducted to identify the target genes of DLEU2 and miR-455-3p,and the effects of miR-455-3p inhibitor/mimic on cell growth of cervical carcinoma and PI3K/AKT signaling pathway were examined.The effect of sh-DLEU2 on tumor growth in vivo was tested by tumor-bearing experiment in nude mice.Results:DLEU2 expression in cervical carcinoma tissues and cell lines was significantly up-regulated (P<0.01).sh-DLEU2 inhibited the proliferation,migration,invasion (P<0.01),and promoted apoptosis (P<0.001) of Hela and SiHa cells.It was confirmed that DLEU2 combined with miR-455-3p.OTUD7B acted as a target gene for miR-455-3p.miR-455-3p inhibitor promoted cell malignant development and activated PI3K/AKT signaling pathway,whereas sh-DLEU2 reversed its impacts (P<0.01).miR-455-3p mimic also partially reversed the effects of Oe-OTUD7B on cells (P<0.01).Furthermore,sh-DLEU2 inhibited the growth of tumor-bearing tissue in nude mice (P<0.01).Conclusion:DLEU2 activates PI3K/AKT signaling pathway through miR-455-3p/OTUD7B axis to promote the malignant development of cervical carcinoma.
Keywords:cervical carcinoma  DLEU2  miR-455-3p  OTUD7B  PI3K/AKT signaling pathway
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