山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (12): 23-28.doi: 10.6040/j.issn.1671-7554.0.2020.0817
王宝金1,赵欣欣1,李霞1,马倩1,王新月1,孙阳2,史中娜1
WANG Baojin1, ZHAO Xinxin1, LI Xia1, MA Qian1, WANG Xinyue1, SUN Yang2, SHI Zhongna1
摘要: 目的 探讨miR-203靶向抑制Survivin对卵巢癌SKOV3及OVCAR3细胞增殖、迁移及侵袭的影响。 方法 构建过表达miR-203、Survivin及空白对照组的慢病毒载体,转染卵巢癌SKOV3和OVCAR3细胞,嘌呤霉素筛选后构建空白对照组、过表达miR-203组、过表达Survivin组及过表达miR-203联合Survivin组卵巢癌细胞系。Western blotting方法测定各组卵巢癌细胞中Survivin及上皮-间质转化(EMT)相关蛋白的表达;MTT和平板克隆实验检测卵巢癌细胞增殖能力的改变;Transwell实验检测对细胞迁移和侵袭能力的影响。 结果 (1) 过表达miR-203抑制Survivin的表达及EMT(P<0.05);(2) MTT、平板克隆实验及transwell实验显示,与空白对照组相比,过表达miR-203组能够抑制卵巢癌细胞的增殖、迁移和侵袭(P<0.05);而过表达Survivin逆转了miR-203对卵巢癌的抑制作用(P<0.05)。 结论 miR-203通过靶向Survivin抑制EMT从而抑制卵巢癌的增殖、迁移及侵袭,miR-203/Survivin/EMT轴有望成为卵巢癌治疗的新靶点。
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| [1] 陆衡, 刘延国, 李曙光, 等. YKL-40对卵巢癌SKOV-3细胞迁移能力的影响[J]. 山东大学学报(医学版), 2017, 55(1): 33-38. LU Heng, LIU Yanguo, LI Shuguang, et al. Regulation of epithelial ovarian carcinoma SKOV-3 cell migration by YKL-40 and the underlying mechanism [J]. Journal of Shandong University, 2017, 55(1): 33-38. [2] Wu X, Liu X. Analysis of the expression of D-dimer, CD147 and miR203 and their correlation in gastric cancer[J]. Pak J Med Sci, 2019, 35(2): 443-447. [3] Piasecka D, Braun M, Kordek R, et al. MicroRNAs in regulation of triple-negative breast cancer progression[J]. J Cancer Res Clin Oncol, 2018, 144(8): 1401-1411. [4] You A, Fu L, Li Y, et al. MicroRNA-203 restrains epithelial-mesenchymal transition, invasion and migration of papillary thyroid cancer by downregulating AKT3[J]. Cell Cycle, 2020, 19(10): 1105-1121. [5] Wang Q, Yang G, Jiang Y, et al. XB130, regulated by miR-203, miR-219, and miR-4782-3p, mediates the proliferation and metastasis of non-small-cell lung cancer cells[J]. Mol Carcinog, 2020, 59(5): 557-568. [6] Zeng S, Liu S, Feng J, et al. MicroRNA-32 promotes ovarian cancer cell proliferation and motility by targeting SMG1[J]. Oncol Lett, 2020, 20(1): 733-741. [7] Zhang Y, Zhou SY, Yan HZ, et al. miR-203 inhibits proliferation and self-renewal of leukemia stem cells by targeting survivin and Bmi-1[J]. Sci Rep, 2016, 6: 19995. doi:10.1038/srep19995. [8] Le F, Luo P, Ouyang Q, et al. LncRNA WT1-AS downregulates Survivin by upregulating miR-203 in papillary thyroid carcinoma[J]. Cancer Manag Res, 2020, 12: 443-449. doi: 10.2147/CMAR.S232294.eCollection 2020. [9] Wang B, Li X, Zhao G, et al. miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway[J]. J Exp Clin Cancer Res, 2018, 37(1): 235-243. [10] Qian XQ, Tang SS, Shen YM, et al. Notch1 affects chemo-resistance through regulating epithelial-mesenchymal transition(EMT)in epithelial ovarian cancer cells[J]. Int J Med Sci, 2020, 17(9): 1215-1223. [11] Scalici JM, Arapovic S, Saks EJ, et al. Mesothelium expression of vascular cell adhesion molecule-1(VCAM-1)is associated with an unfavorable prognosis in epithelial ovarian cancer(EOC)[J]. Cancer, 2017, 123(6): 977-984. [12] Chen X, Zhang J, Zhang Z, et al. Cancer stem cells, epithelial-mesenchymal transition, and drug resistance in high-grade ovarian serous carcinoma[J]. Hum Pathol, 2013, 44(11): 2373-2384. [13] Ghafouri-Fard S, Shoorei H, Taheri M. miRNA profile in ovarian cancer[J]. Exp Mol Pathol, 2020, 113: 104381. doi:10.1016/j.yexmp.2020.104381. [14] Kim JS, Choi DW, Kim CS, et al. MicroRNA-203 induces apoptosis by targeting bmi-1 in YD-38 oral cancer cells[J]. Anticancer Res, 2018, 38(6): 3477-3485. [15] Zhang K, Dai L, Zhang B, et al. miR-203 is a direct transcriptional target of E2F1 and causes G1 arrest in esophageal cancer cells[J]. J Cell Physiol, 2015, 230(4): 903-910. [16] Gao P, Wang S, Jing F, et al. microRNA-203 suppresses invasion of gastric cancer cells by targeting ERK1/2/Slug/ E-cadherin signaling[J]. Cancer Biomark, 2017, 19(1): 11-20. [17] Deng B, Wang B, Fang J, et al. MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2[J]. Sci Rep, 2016, 6: 28301. doi:10.1038/srep28301. [18] Chi Y, Jin Q, Liu X, et al. miR-203 inhibits cell proliferation, invasion, and migration of non-small-cell lung cancer by downregulating RGS17[J]. Cancer Sci, 2017, 108(12): 2366-2372. [19] Shen J, Zhang J, Xiao M, et al. miR-203 Suppresses bladder cancer cell growth and targets twist[J]. Oncol Res, 2018, 26(8): 1155-1165. [20] Lin J, Wang L, Gao J, et al. MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells[J]. Exp Ther Med, 2017, 14(3): 2702-2708. [21] Martínez-García D, Manero-Rupérez N, Quesada R, et al. Therapeutic strategies involving survivin inhibition in cancer[J]. Med Res Rev, 2019, 39(3): 887-909. [22] He XJ, Zhang Q, Ma LP, et al. Aberrant alternative polyadenylation is responsible for Survivin up-regulation in ovarian cancer[J]. Chin Med J(Engl), 2016, 129(10): 1140-1146. [23] Mittal V. Epithelial mesenchymal transition in tumor metastasis[J]. Annu Rev Pathol, 2018, 13: 395-412. doi: 10.1146/annurev-pathol-020117-043854. [24] Qian XQ, Tang SS, Shen YM, et al. Notch1 affects chemo-resistance through regulating epithelial-mesenchymal transition(EMT)in epithelial ovarian cancer cells[J]. Int J Med Sci, 2020, 17(9): 1215-1223. [25] Wang Z, Liu Y, Wang M, et al. Effects of miR-492 on migration, invasion, EMT and prognosis in ovarian cancer by targeting SOX7[J]. J buon, 2020, 25(2): 797-804. [26] Zhao G, Guo Y, Chen Z, et al. miR-203 functions as a tumor Suppressor by inhibiting epithelial to mesenchymal transition in ovarian cancer[J]. J Cancer Sci Ther, 2015, 7(2): 34-43. |
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