基于Oncomine 数据库研究PDE4D基因在卵巢癌中的表达及血根碱的调控作用

邓玥; 邹丹; TounaAbdelkerim Barh; 杨丽华

doi:10.12259/j.issn.2095-610X.S20220303

基于Oncomine 数据库研究PDE4D基因在卵巢癌中的表达及血根碱的调控作用

doi: 10.12259/j.issn.2095-610X.S20220303

昆明医科大学第二附属医院妇科，云南昆明　650101

基金项目: 国家自然科学基金资助项目（81960469）；云南省“万人计划”名医专项（YNWR-MY-2019-037）；昆明医科大学卵巢癌临床及基础研究科技创新团队（CXTD202008）；昆明医科大学研究生创新基金资助项目（2021S235）

详细信息

作者简介:
邓玥（1997～），女，云南丽江人，在读硕士研究生，主要从事妇科肿瘤及妇科内分泌临床工作

通讯作者:
杨丽华，E-mail：lihuazhang33@sina.com

中图分类号: R3;R71
计量
- 文章访问数: 3548
- HTML全文浏览量: 1769
- PDF下载量: 40
- 被引次数: 0
出版历程
- 收稿日期: 2022-01-02
- 网络出版日期: 2022-02-18
- 刊出日期: 2022-03-22

Expression of PDE4D Gene in Ovarian Cancer Based on Oncomine and the Regulation of Sanguinarine

Dept. of Gynecology，The 2nd Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101，China

摘要

摘要: 目的通过深度挖掘Oncomine数据库中PDE4D在卵巢癌的研究数据，分析PDE4D基因在卵巢癌中的表达变化，并进行细胞实验研究血根碱对卵巢癌细胞中PDE4D基因表达的影响。方法 PharmMapper数据库查询与血根碱药效基团匹配的作用靶点，收集Oncomine数据库 PDE4D在卵巢癌中的研究数据，进一步分析PDE4D在卵巢癌中的表达变化。将卵巢癌SKOV3和A2780细胞分成对照组和血根碱组，CCK8和RT-qPCR法分别检测血根碱对卵巢癌A2780、SKOV3细胞增殖及PDE4D mRNA表达的影响。结果 PDE4D是与血根碱药效基团匹配的作用靶点。Oncomine数据库中共查询到6项正常卵巢组织和卵巢癌组织PDE4D基因的研究，且PDE4D在不同类型的卵巢癌组织中均呈高表达（P < 0.05）。细胞实验表明，与对照组相比，血根碱组卵巢癌A2780、SKOV3细胞增殖被明显抑制，PDE4D mRNA表达降低，差异均有统计学意义（P < 0.05）。结论卵巢癌组织中PDE4D基因呈高表达，血根碱抑制卵巢癌细胞生长可能与下调PDE4D表达相关。
- 卵巢癌 /
- PDE4D /
- Oncomine数据库 /
- 血根碱
Abstract: Objective To investigate the expression and clinical significance of PDE4D in ovarian cancer by excavating gene information in Oncomine and explore the effect of sanguinarine on PDE4D by cells experiment. Methods PharmMapper was used to find the targets matched with the pharmacodynamic groups of sanguinarine. The gene information about PDE4D in ovarian cancer research was collected in Oncomine, and the expression level was analyzed. The A2780 and SKOV3 ovarian carcinoma cells were divided into control group and sanguinarine group. CCK8 and RT-qPCR were used to detect the effects of sanguinarine on the proliferation and PDE4D mRNA expression of A2780 and SKOV3 cells. Results PDE4D was the target matched with the pharmacodynamic group of sanguinarine. There were 6 studies referred to PDE4D in ovarian cancer and normal sample collected in the Oncomine. The expression of PDE4D in tumor tissues was significantly higher than that in normal （P < 0.05）. The cell experiments showed that compared with the control group, the proliferation of A2780 and SKOV3 cells was significantly inhibited and the expression of PDE4D mRNA was decreased in the sanguinarine group, with statistical significance （P < 0.05）. Conclusions PDE4D gene may play a role in the occurrence and development of ovarian cancer, and sanguinarine can inhibit the growth of ovarian cancer cells, which may be related to the down-regulation of PDE4D expression.
- Ovarian cancer /
- PDE4D /
- Oncomine /
- Sanguinarine

HTML全文

图 1 Oncomine数据库中PDE4D在卵巢癌中的表达

Figure 1. Expression of PDE4D in ovarian cancer in Oncomine

下载: 全尺寸图片幻灯片

图 2 Oncomine数据库中PDE4D在不同卵巢癌芯片中的表达

Figure 2. Expression of PDE4D in different ovarian cancer studies in Oncomine

下载: 全尺寸图片幻灯片

图 3 血根碱对卵巢癌A2780、SKOV3细胞增殖的影响

A：对照组A2780细胞（×100）；B：血根碱组A2780细胞（×100）；C：对照组SKOV3细胞（×100）；D：血根碱组SKOV3细胞（×100）；E：CCK8法检测的细胞存活率。与对照组比较，^**P < 0.01；^***P < 0.001。

Figure 3. Effect of Sanguinarine on proliferation of A2780 and SKOV3 cells

下载: 全尺寸图片幻灯片

图 4 血根碱对卵巢癌A2780、SKOV3细胞PDE4D mRNA表达的影响

与对照组比较，^*P < 0.05，^**P < 0.01。

Figure 4. Effect of Sanguinarine on PDE4D mRNA expression of A2780 and SKOV3 cells

下载: 全尺寸图片幻灯片

参考文献(26)

[1]	Zhang Q,Madden N E,Wong A S T,et al. The role of endocrine G protein-coupled receptors in ovarian cancer progression[J]. Frontiers in Endocrinology,2017,8:66.
[2]	Hsien Lai S,Zervoudakis G,Chou J,et al. PDE4 subtypes in cancer[J]. Oncogene,2020,39(19):3791-3802. doi: 10.1038/s41388-020-1258-8
[3]	Fu C,Guan G,Wang H. The anticancer effect of sanguinarine:A review[J]. Current Pharmaceutical Design,2018,24(24):2760-2764. doi: 10.2174/1381612824666180829100601
[4]	Liu X, Ouyang S, Yu B, et al. Pharm Mapper server: a web server for potential drug target identification using pharmacophore mapping approach[J]. Nucleic Acids Research, 2010, 38 （Web Server issue）: W609-614.
[5]	Rhodes D R,Yu J,Shanker K,et al. ONCOMINE:a cancer microarray database and integrated data-mining platform[J]. Neoplasia (New York,NY),2004,6(1):1-6. doi: 10.1016/S1476-5586(04)80047-2
[6]	Yu H,Touna A,Yin X,et. al. Identification of differentially expressed genes and biological pathways in sanguinarine-treated ovarian cancer by integrated bioinformatics analysis[J]. Pharmacognosy Magazine,2021,17(73):106-113. doi: 10.4103/pm.pm_111_20
[7]	李京辉,朱明,曲海,等. miR-490-3p调控SW1990胰腺癌细胞上皮间充质转化[J]. 昆明医科大学学报,2021,42(3):10-17. doi: 10.12259/j.issn.2095-610X.S20210305
[8]	Lin D C,Xu L,Ding L W,et al. Genomic and functional characterizations of phosphodiesterase subtype 4D in human cancers[J]. Proceedings of the National Academy of Sciences of the United States of America,2013,110(15):6109-6114. doi: 10.1073/pnas.1218206110
[9]	Pullamsetti S S,Banat G A,Schmall A,et al. Phosphodiesterase-4 promotes proliferation and angiogenesis of lung cancer by crosstalk with HIF[J]. Oncogene,2013,32(9):1121-1134. doi: 10.1038/onc.2012.136
[10]	Rahrmann E P,Collier L S,Knutson T P,et al. Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screen[J]. Cancer Research,2009,69(10):4388-4397. doi: 10.1158/0008-5472.CAN-08-3901
[11]	Liu F,Ma J,Wang K,et al. High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma[J]. Journal of Cancer,2019,10(25):6252-6260. doi: 10.7150/jca.35443
[12]	Cao B,Wang K,Liao J M,et al. Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation[J]. eLife,2016,5:e15978. doi: 10.7554/eLife.15978
[13]	Muntean D M,Sturza A,Pavel I Z,et al. Modulation of cancer metabolism by phytochemicals-a brief overview[J]. Anti-cancer Agents in Medicinal Chemistry,2018,18(5):684-692. doi: 10.2174/1871520617666171114102218
[14]	梁宏. 基于生物信息学挖掘卵巢癌顺铂耐药机制及潜在治疗药物 [D]. 昆明: 昆明医科大学硕士论文, 2016.
[15]	Yu Y,Luo Y,Fang Z,et al. Mechanism of sanguinarine in inhibiting macrophages to promote metastasis and proliferation of lung cancer via modulating the exosomes in A549 cells[J]. OncoTargets and Therapy,2020,13:8989-9003. doi: 10.2147/OTT.S261054
[16]	Rahman A,Pallichankandy S,Thayyullathil F,et al. Critical role of H(2)O(2) in mediating sanguinarine-induced apoptosis in prostate cancer cells via facilitating ceramide generation,ERK1/2 phosphorylation,and Par-4 cleavage[J]. Free Radical Biology & Medicine,2019,134:527-544.
[17]	Khan A Q,Mohamed E A N,Hakeem I,et al. Sanguinarine induces apoptosis in papillary thyroid cancer cells via generation of reactive oxygen species[J]. Molecules (Basel,Switzerland),2020,25(5):1229. doi: 10.3390/molecules25051229
[18]	Fan H N,Chen W,Peng S Q,et al. Sanguinarine inhibits the tumorigenesis of gastric cancer by regulating the TOX/DNA-PKcs/ KU70/80 pathway[J]. Pathology,Research and Practice,2019,215(11):152677.
[19]	Gong X,Chen Z,Han Q,et al. Sanguinarine triggers intrinsic apoptosis to suppress colorectal cancer growth through disassociation between STRAP and MELK[J]. BMC Cancer,2018,18(1):578. doi: 10.1186/s12885-018-4463-x
[20]	Ma Y,Yu W,Shrivastava A,et al. Sanguinarine inhibits pancreatic cancer stem cell characteristics by inducing oxidative stress and suppressing sonic hedgehog-Gli-Nanog pathway[J]. Carcinogenesis,2017,38(10):1047-1056. doi: 10.1093/carcin/bgx070
[21]	Sarkhosh-Inanlou R,Molaparast M,Mohammadzadeh A,et. al. Sanguinarine enhances cisplatin sensitivity via glutathione depletion in cisplatin-resistant ovarian cancer (A2780) cells[J]. Chemical Biology & Drug Design,2020,95(2):215-223.
[22]	Zhang S,Leng T,Zhang Q,et. al. Sanguinarine inhibits epithelial ovarian cancer development via regulating long non-coding RNA CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathway[J]. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie,2018,102:302-308.
[23]	赵洪波,王妍妍,冷天艳,等. 血根碱对紫杉醇耐药卵巢癌A2780/taxol细胞生长及化疗敏感性影响的研究[J]. 实用妇产科杂志,2018,34(4):268-272.
[24]	Zhang H,Kong Q,Wang J,et al. Complex roles of cAMP-PKA-CREB signaling in cancer[J]. Experimental Hematology & Oncology,2020,9(1):32.
[25]	Huang H,Wang Y,Kandpal M,et al. FTO-dependent N (6)-methyladenosine modifications inhibit ovarian cancer stem cell self-renewal by blocking cAMP signaling[J]. Cancer Research,2020,80(16):3200-3214. doi: 10.1158/0008-5472.CAN-19-4044
[26]	Gong S,Chen Y,Meng F,et al. Roflumilast enhances cisplatin-sensitivity and reverses cisplatin-resistance of ovarian cancer cells via cAMP/PKA/CREB-FtMt signalling axis[J]. Cell Proliferation,2018,51(5):e12474. doi: 10.1111/cpr.12474

相关文章(20)

[1]	彭青兰, 罗佳露, 余佳仪, 汪凯鑫, 吴芳, 许传志. 基于FAERS数据库的阿奇霉素不良事件的信号挖掘与分析, 昆明医科大学学报.
[2]	赵丽珠, 董莹, 邓玥, 杨丽华. 基于单细胞测序技术分析上皮细胞相关基因与卵巢癌患者预后的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240402
[3]	王兴粉, 邓玥, 杨丽华. 卵巢癌脂质代谢相关基因预后模型的构建及免疫浸润分析, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240403
[4]	蒋亚萍, 杨宏英, 汪昊涵, 宁显灵, 杨谢兰. 不同肠道手术方式对肠道受侵上皮性卵巢癌患者预后的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230109
[5]	颜怡君, 杨宏英, 张红平, 李政, 贾岳, 赵敏. 基于TCGA数据库筛选宫颈鳞状细胞癌潜在的预后标志物及验证, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230808
[6]	廉阳秧, 岳红萍, 端娅, 胡红文, 罗芳. miRNA-15a/16调控Bmi-1蛋白在卵巢癌顺铂化疗耐药中的作用, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20231204
[7]	王艳飞, 马娟, 杨云巧. 沙库巴曲缬沙坦对射血分数降低合并低血压心衰患者的临床疗效及安全性的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20221117
[8]	杨霄彦, 郝春光, 张志坚. 孕激素通过HOXA9对人卵巢癌细胞增殖和迁移的机制研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20221022
[9]	徐丽秀, 美力班·吐尔逊, 克热曼·牙库甫. miR-181a在卵巢癌细胞中对顺铂的耐药作用, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220131
[10]	刘钧, 许冰莹. Expressmarker16+10Y试剂盒一致性评价及在DNA数据库建设中的应用, 昆明医科大学学报.
[11]	倪慧霞, 赵卫, 胡继红, 王滔. 基于CTA数据源3D打印技术在神经介入教学中的应用, 昆明医科大学学报.
[12]	张璐, 吕乐春, 吴艳瑞, 袁方, 唐文羽, 邹显强, 李春银, 赵敏. 基于GEO数据库进行人类皮肤芯片核苷酸切除修复基因XPA表达的差异性, 昆明医科大学学报.
[13]	胡万芹, 赵洪波, 梁宏, 赵庆华, 杨丽华. 顺铂耐药卵巢癌的差异表达基因和信号通路富集分析, 昆明医科大学学报.
[14]	胡玉崇, 陆景坤, 崔梦瑶. PTEN及Caspase-3可能参与卵巢癌铂类耐药的机制, 昆明医科大学学报.
[15]	王春龙, 韩丹, 文亮. 间皮素与肿瘤诊治的相关研究进展, 昆明医科大学学报.
[16]	杨涵. Bmi-1基因在不同类型上皮性卵巢癌组织中的表达及临床意义, 昆明医科大学学报.
[17]	张燕. 云南高校地方特色数据库的文献资源特色及其收集来源分析, 昆明医科大学学报.
[18]	杨丽华. 抗整合素αⅤβ3单抗抑制上皮性卵巢癌血管及肿瘤生成的实验研究, 昆明医科大学学报.
[19]	. 多种载体人体生物检材直扩方法在DNA数据库建库中的实验研究, 昆明医科大学学报.
[20]	梁荣毕. 背驮式原位肝移植麻醉中血酸-碱平衡和电解质的变化, 昆明医科大学学报.