lncRNA DLEU2/miR-455-3p/OTUD7B轴通过PI3K/AKT信号通路促进宫颈癌恶性发展  

lncRNA DLEU2/miR-455-3p/OTUD7B axis promotes the malignant progression of cervical carcinoma by regulating PI3K/AKT signaling pathway

作　　者：冯钰玲 顾燕楠 凌剑梅 丁易钤[2] FENG Yuling;GU Yannan;LING Jianmei;DING Yiqian(Department of Obstetrics and Gynecology,Nantong Maternal and Child Health Hospital,Jiangsu Nantong 226000,China;Department of Gynecology,Nantong Maternal and Child Health Hospital,Jiangsu Nantong 226000,China)

机构地区：[1]南通市妇幼保健院妇产科,江苏南通226000 [2]南通市妇幼保健院妇科,江苏南通226000

出　　处：《现代肿瘤医学》2023年第14期2614-2623,共10页Journal of Modern Oncology

基　　金：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。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.

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

分 类 号：R737.33[医药卫生—肿瘤]