miR-200b-3p和PAK2 mRNA在耐药卵巢癌组织中的表达及其临床意义

doi:10.3969/j.issn.1004-616x.2019.03.008

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (3): 216-221.doi: 10.3969/j.issn.1004-616x.2019.03.008

miR-200b-3p和PAK2 mRNA在耐药卵巢癌组织中的表达及其临床意义

万树泉¹, 魏丽军², 王福花³, 曾勇²

1. 山西医科大学第二临床医学院, 山西太原 030001;
2. 山西医科大学附属肿瘤医院妇一科, 山西太原 030013;
3. 山西医科大学附属肿瘤医院分子生物室, 山西太原 030013

收稿日期:2018-12-03 修回日期:2019-04-23 出版日期:2019-05-31 发布日期:2019-05-31
通讯作者: 魏丽军,E-mail:475960322@qq.com E-mail:475960322@qq.com
作者简介:万树泉,E-mail:1305158369@qq.com。

Expression of miR-200b-3p and PAK2 in chemotherapy-resistant and sensitive ovarian cancers

WAN Shuquan¹, WEI Lijun², WANG Fuhua³, ZENG Yong²

1. Second Clinical Medical College of Shanxi Medical University, Taiyuan 030001;
2. Department of Gynecology, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan 030013;
3. Department of Molecular Biology, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan 030013, Shanxi, China

Received:2018-12-03 Revised:2019-04-23 Online:2019-05-31 Published:2019-05-31

摘要/Abstract

摘要： 目的：探讨化疗耐药和化疗敏感患者卵巢癌组织中miR-200b-3p和PAK2 mRNA的表达水平及其临床意义。方法：采用生物信息学方法结合文献综合分析初步预测miR-200b-3p在卵巢癌组织中的靶基因为PAK2，收集山西省肿瘤医院2015-2018年的25例卵巢癌化疗耐药患者组织样本（耐药组）和25例卵巢癌化疗敏感患者组织样本（敏感组），采用实时荧光定量PCR法（qPCR）检测miR-200b-3p和PAK2 mRNA的相对表达量。比较两组患者肿瘤组织中miR-200b-3p和PAK2 mRNA的表达差异，并分析miR-200b-3p、PAK2 mRNA表达水平与上皮性卵巢癌患者临床病理指标的关系。结果：耐药组卵巢癌患者癌组织miR-200b-3p的表达水平显著高于敏感组卵巢癌患者，是敏感组的15.78倍；耐药组卵巢癌患者癌组织PAK2 mRNA的表达水平显著低于敏感组卵巢癌患者，是敏感组的0.03。miR-200b-3p和PAK2 mRNA表达水平呈负相关（r=-0.560，P<0.01）。结论：miR-200b-3p在化疗耐药性卵巢癌组织中过表达，可能是通过靶向调控PAK2 mRNA参与调节化疗耐药和促进卵巢癌转移。

关键词: 卵巢癌, 化疗耐药, miR-200b-3p, PAK2 mRNA

Abstract: OBJECTIVE: To investigate the expression and clinical significance of miR-200b-3p and PAK2 mRNA in chemotherapy-resistant and sensitive ovarian cancers. METHODS: Bioinformatics method combined with comprehensive literature analyses were used to predict the target gene of miR-200b-3p as PAK2. From 2015 to 2018,25 tissue samples from patients with chemo-resistant ovarian cancers and 25 from chemo-sensitive ovarian cancers were collected from Shanxi Provincial Cancer Hospital. Relative expression of miR-200b-3p and PAK2 mRNA from the two groups of tissues were detected by using quantitative real-time PCR (qPCR). Their expression levels and clinic-pathological parameters of the two groups of cancer patients were compared. RESULTS:The expression level of miR-200b-3p was 15.78 times and significantly higher in the chemo-resistant ovarian cancer tissues than the sensitive ones. However, the expression level of PAK2 mRNA was 0.03 times and significantly lower in the resistant and in the sensitive tissues. The expression levels of miR-200b-3p and PAK2 mRNA were significantly correlated with the clinical stage and lymph node metastasis of ovarian cancer patients (P<0.05). CONCLUSION:Our data show that over-expression of miR-200b-3p and regulation of PAK2 mRNA were involved in the expression of chemoresistance and the promotion of ovarian cancer metastasis.

Key words: ovarian cancer, chemotherapy resistance, miR-200b-3p, PAK2 mRNA

中图分类号:

R711.75

万树泉, 魏丽军, 王福花, 曾勇. miR-200b-3p和PAK2 mRNA在耐药卵巢癌组织中的表达及其临床意义[J]. 癌变·畸变·突变, 2019, 31(3): 216-221.

WAN Shuquan, WEI Lijun, WANG Fuhua, ZENG Yong. Expression of miR-200b-3p and PAK2 in chemotherapy-resistant and sensitive ovarian cancers[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(3): 216-221.

参考文献

[1] FREDDIE B, JACQUES F, ISABELLE S, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2018,68(6):394-424.
[2] 何咏竞. 肿瘤标志物联合检测在卵巢疾病诊断中的临床价值探讨[J]. 国际检验医学杂志,2018,39(7):888-890.
[3] LEE R C, FEINBAUM R L, AMBROS V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin -14[J]. Cell,1993, 75(5):843-854.
[4] DI L G, GAROFALO M, CROCE C M. MicroRNAs in cancer[J]. Annu Rev Pathol,2014,9:287-314.
[5] ZHANG Z, XING T C, CHEN Y H, et al. Exosomemediated miR-200b promotes colorectal cancer proliferation upon TGF-β1 exposure[J]. Biomed Pharmacother, 2018, 106:1135-1143.
[6] MARTA G, ALESSANDRA P, CAMILLO R, et al. Resistance to cancer chemotherapeutic drugs is determined by pivotal microRNA regulators[J]. Am J Cancer Res, 2017,7(6):1350-1371.
[7] YUAN H L, WANG T, ZHANG K H. MicroRNAs as potential biomarkers for diagnosis, therapy and prognosis of gastric cancer[J]. Onco Targets Ther,2018,11:3891-3900.
[8] MENG F,HENSON R,LANG L,et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines[J]. Gastroenterology,2006,130:2113-2129.
[9] YANG X,HU Q,HU L X,et al. miR-200b regulates epithelial-mesenchymal transition of chemo-resistant breast cancer cells by targeting FN1[J]. Discov Med, 2017,24(131):75-85.
[10] ZHU K P,ZHANG C L,MA X L,et al. Fibronectin-1 modulated by the long noncoding RNA OIP5-AS1/miR-200b-3p axis contributes to doxorubicin resistance of osteosarcoma cells[J/OL]. J Cell Physiol, 2018. doi:10. 1002/jcp.27435.
[11] BROZOVIC A, DURAN G E, WANG Y C. The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells[J]. Mol Oncol, 2015, 9(8):1678-1693.
[12] 曾勇,李娜,王福花,等. 卵巢浆液性囊腺癌化疗耐药和化疗敏感组织中的miRNAs差异表达谱检测及生物信息学分析[J]. 现代肿瘤医学,2017,25(12):1870-1875.
[13] PENG Y J,HE X J,CHEN H H,et al. Inhibition of microRNA-299-5p sensitizes glioblastoma cells to temozolomide via the MAPK/ERK signaling pathway[J/OL]. Biosci Rep,2018. doi:10.1042/BSR20181051.
[14] ZHOU P J,ZHANG R,WANG Y,et al. Cepharanthine hydrochloride reverses the MDR1(P-glycoprotein)-mediated esophageal squamous cell carcinoma cell cisplatin resistance through JNK and p53 signals[J]. Oncotarget, 2017,8(67):111144-111160.
[15] SONG H G, WU T Q, XIE D, et al. WBP2 downregulation inhibits proliferation by blocking YAP transcription and the EGFR/PI3K/Akt signaling pathway in triple negative breast cancer[J]. Cell Physiol Biochem, 2018,48(5):1968-1982.
[16] LI B,DING C M,LI Y X,et al. MicroRNA145 inhibits migration and induces apoptosis in human nonsmall cell lung cancer cells through regulation of the EGFR/PI3K/AKT signaling pathway[J]. Oncol Rep, 2018, 40(5):2944-2954.
[17] JIANG N,HJORTH-JENSEN K,HEKMAT O,et al. In vivo quantitative phosphoproteomic profiling identifies novel regulators of castration-resistant prostate cancer growth[J]. Oncogene,2015,34(21):2764-2776.
[18] RADU M, LYLE K, HOEFLICH K P, et al. p21-activated kinase 2 regulates endothelial development and function through the Bmk1/Erk5 pathway[J]. Mol Cell Biol,2015,35(23):3990-4005.
[19] LI X,WEN W H,LIU K D,et al. Phosphorylation of caspase-7 by p21-activated protein kinase (PAK) 2 inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell lines[J]. J Biol Chem,2011,286(25):22291-22299.
[20] LU H Z, LIU S J, ZHANG G, et al. PAK signalling drives acquired drug resistance to MAPK inhibitors in BRAF-mutant melanomas[J]. Nature, 2017, 550(7674):133-136.

miR-200b-3p和PAK2 mRNA在耐药卵巢癌组织中的表达及其临床意义

Expression of miR-200b-3p and PAK2 in chemotherapy-resistant and sensitive ovarian cancers

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 8

编辑推荐

Metrics

本文评价

[1]	马亚南, 吴楠, 金焰. 肿瘤微环境与卵巢癌化疗耐药机制的研究进展[J]. 癌变·畸变·突变, 2021, 33(5): 393-395,400.
[2]	吴异兰, 王晗. 白藜芦醇对肺癌紫杉醇耐药细胞的增殖抑制作用及其机制[J]. 癌变·畸变·突变, 2018, 30(3): 200-203,208.
[3]	谢琛静,刘向云,桂博,崇立明,许丽,潘琦,周莉,孙祖越. Ⅰ-单克隆抗体对人卵巢癌细胞株OC-3-VGH裸鼠皮下移植瘤的抑制作用[J]. 癌变·畸变·突变, 2013, 25(1): 13-17.
[4]	王琦1;田东萍1;李从铸2;钟卫祥1;丁文双1. 人卵巢癌干细胞球的分离与悬浮培养方法[J]. , 2010, 22(2): 141-145.
[5]	陈旻(综述);李从铸(审校). B7-H4与卵巢癌早期诊断的相关研究进展[J]. , 2009, 21(6): 479-481.
[6]	朱壮彦1, 富晓敏1, 穆雅琴2, 李拴明2, 赵富玺2, 糜若然3. 紫杉醇作用卵巢癌细胞系HO-8910后CYP1B1 mRNA及蛋白表达差异的研究[J]. , 2009, 21(3): 214-217.
[7]	赵群（综述）/ 邓小虹（审校）. 蛋白质组学在卵巢癌诊治中的研究进展[J]. , 2006, 18(3): 252-254.
[8]	刘　颖　综述; 史惠蓉　审校. 遗传性乳腺卵巢癌的易感基因BRCA1 、BRCA2 研究进展[J]. , 2002, 14(1): 54-057.