您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2017, Vol. 55 ›› Issue (4): 39-43.doi: 10.6040/j.issn.1671-7554.0.2016.515

• 基础医学 • 上一篇    下一篇

MiR- 498通过下调FOXM1抑制肺腺癌细胞上皮充质细胞转化

唐曦1,胡娅2,徐炎华1,汪春林1,邱萍1,王向辉3   

  1. 1.华中科技大学同济医学院附属荆州医院肿瘤中心, 湖北 荆州 434020;2.长江大学医学院, 湖北 荆州 434023;3.华中科技大学同济医学院附属荆州医院胸外科, 湖北 荆州 434020
  • 收稿日期:2016-05-09 出版日期:2017-04-10 发布日期:2017-04-10
  • 通讯作者: 胡娅. E-mail:huy12@126.com E-mail:huy12@126.com
  • 基金资助:
    湖北省教育厅2013年度科研项目计划(B2013280);2011~2012年度湖北省卫生厅中医药中西医结合科研项目计划(2012Z-Y31)

MiR- 498 inhibits A549 cells EMT by targeting FOXM1

TANG Xi1, HU Ya2, XU Yanhua1, WANG Chunlin1, QIU Ping1, WANG Xianghui3   

  1. 1. Cancer Center, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jingzhou 434020, Hubei, China;
    2. Medical College, Yangtze University, Jingzhou 434023, Hubei, China;
    3. Department of Cardiothoracic Surgey, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jingzhou 434020, Hubei, China
  • Received:2016-05-09 Online:2017-04-10 Published:2017-04-10

摘要: 目的 研究miR- 498对肺腺癌细胞上皮充质细胞转化(EMT)的影响及相关机制。 方法 转染miR- 498mimic和miR-NC至离体培养的A549细胞中,将细胞分为空白对照组、miR- 498组和空质粒组3组,Transwell法检测细胞迁移侵袭情况,Western blotting检测A549细胞中E-cadherin、fibronectin、vimentin、FOXM1的表达,利用荧光素酶实验验证miR- 498的靶基因;再通过转染过表达FOXM1的质粒至A549细胞,将细胞分为miR- 498组、miR- 498+FOXM1组、miR- 498+空质粒组,检测A549细胞的上述生物学指标。 结果 与空质粒组相比,转染miR- 498mimic后,A549细胞中E-cadherin表达增加(P=0.001),fibronectin、vimentin、FOXM1表达减少(P均<0.01),A549细胞的迁移能力减少(P=0.001);荧光素酶实验结果显示,miR- 498能够显著降低FOXM1-3'-UTR 质粒的荧光素活性(P=0.001);与miR- 498+空质粒组相比,转染过表达FOXM1质粒后,A549细胞中E-cadherin表达减少(P=0.002),fibronectin、vimentin表达增加(P均<0.001),A549细胞的迁移能力增加(P=0.001)。 结论 miR- 498通过下调FOXM1从而抑制A549细胞的EMT。

关键词: miR- 498, 上皮充质细胞转化, 肺腺癌, FOXM1

Abstract: Objective To investigate the effect of miR- 498 on A549 cells epithelial-to-mesenchymal transition(EMT)and its correlated mechanism. Methods After miR- 498 was transfected into A549 cells, the cells were divided into control group, empty vector group and miR- 498 group; Transwell assay was employed to test the migration ability of A549 cells, Western blotting was used to investigate the expressions of E-cadherin, fibronectin, vimentin and FOXM1 in A549 cells. Luciferase assay was used to confirmed whether FOXM1-3'-UTR was the target gene of miR- 498. Then, the cells were divided into miR- 498 group, miR- 498 + FOXM1 group, and miR- 498 + empty plasmid group, and the above biological indicators of A549 cells were detected again. Results Compared with the empty vector group, the expression of E-cadherin was increased(P=0.001), the expression of fibronectin, vimentin and FOXM1were decreased(all P<0.01), and the migration ablitiy of A549 cells was decreased in the miR- 498 group(P=0.001); the Luciferase activity of the FOXM1-3'-UTR plasmid was significantly suppressed by miR- 498(P=0.001); over-expression of FOXM1 could reverse the effect of miR- 498 on A549. Conclusion miR- 498 inhibits A549 cells EMT by down-regulating FOXM1 expression.

Key words: Lung adenocarcinoma, miR- 498, FOXM1, Epithelial-to-mesenchymal transition

中图分类号: 

  • R734.2
[1] Bao B, Wang Z, Ali S, et al. Over-expression of FoxM1 leads to epithelial-mesenchymal transition and cancer stem cell phenotype in pancreatic cancer cells[J]. J Cell Biochem, 2011, 112(9): 2296-2306.
[2] Chen QY, JIao DM, Wang J, et al. miR-206 regulates cisplatin resistance and EMT in human lung adenocarcinoma cells partly by targeting MET[J]. Oncotarget, 2016, 7(17):24510-24526.
[3] Tang WB, Ling GH, Sun L, et al. Smad anchor for receptor activation regulates high glucose-induced EMT via modulation of Smad2 and Smad3 activities in renal tubular epithelial cells[J]. Nephron, 2015, 130(3): 213-220.
[4] Guo L, Peng W, Tao J, et al. Hydrogen sulfide inhibits transforming growth factor-beta1-induced EMT via wnt/catenin pathway[J]. PLoS One, 2016, 11(1): e0147018. doi: 10.1371/journal.pone.0147018.
[5] Sun Y, Yu X, Bai Q. miR-204 inhibits invasion and epithelial-mesenchymal transition by targeting FOXM1 in esophageal cancer[J]. Int J Clin Exp Pathol, 2015, 8(10): 12775-12783.
[6] Gopalan V, Smith RA, Lam AK. Downregulation of microRNA- 498 in colorectal cancers and its cellular effects[J]. Exp Cell Res, 2015, 330(2): 423-428.
[7] Matamala N, Vargas MT, Gonzalez-Campora R, et al. MicroRNA deregulation in triple negative breast cancer reveals a role of miR- 498 in regulating BRCA1 expression[J]. Oncotarget, 2016, 7(15): 20068-20079.
[8] Liu R, Liu F, Li L, et al. MiR- 498 regulated FOXO3 expression and inhibited the proliferation of human ovarian cancer cells[J]. Biomed Pharmacother, 2015, 72: 52-57.
[9] Wang M, Zhang Q, Wang J, et al. MicroRNA- 498 is downregulated in non-small cell lung cancer and correlates with tumor progression[J]. J Cancer Res Ther, 2015, 11(Suppl 1): C107-C111.
[10] Li Z, Ying X, Chen H, et al. MicroRNA-194 inhibits the epithelial-mesenchymal transition in gastric cancer cells by targeting FoxM1[J]. Dig Dis Sci, 2014, 59(9): 2145-2152.
[11] Ke Y, Zhao W, Xiong J, et al. miR-149 inhibits non-small-cell lung cancer cells EMT by targeting FOXM1[J]. Biochem Res Int, 2013, 2013: 506731. doi:10.1155/2013/506731.
[12] Tang O, Chen XM, Shen S, et al. MiRNA-200b represses transforming growth factor-beta1-induced EMT and fibronectin expression in kidney proximal tubular cells[J]. Am J Physiol Renal Physiol, 2013, 304(10): F1266-F1273.
[13] Li Y, An H, Pang J, et al. MicroRNA profiling identifies miR-129-5p as a regulator of EMT in tubular epithelial cells[J]. Int J Clin Exp Med, 2015, 8(11): 20610-20616.
[14] Li J, Wang Y, Luo J, et al. miR-134 inhibits epithelial to mesenchymal transition by targeting FOXM1 in non-small cell lung cancer cells[J]. FEBS Lett, 2012, 586(20): 3761-3765.
[15] Tan X, Fu Y, Chen L, et al. miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer[J]. Oncotarget, 2016, 7(1): 293-307.
[16] Liu Z, Jin ZY, Liu CH, et al. MicroRNA-21 regulates biological behavior by inducing EMT in human cholangiocarcinoma[J]. Int J Clin Exp Pathol, 2015, 8(5): 4684-4694.
[17] Li S, Qin X, Li Y, et al. MiR-133a suppresses the migration and invasion of esophageal cancer cells by targeting the EMT regulator SOX4[J]. Am J Transl Res,2015, 7(8): 1390-1403.
[18] Sun Y, Wang H, Liu M, et al. Resveratrol abrogates the effects of hypoxia on cell proliferation, invasion and EMT in osteosarcoma cells through downregulation of the HIF-1alpha protein[J]. Mol Med Rep, 2015, 11(3): 1975-1981.
[19] Kogo R, How C, Chaudary N, et al. The microRNA-218~Survivin axis regulates migration, invasion, and lymph node metastasis in cervical cancer[J]. Oncotarget, 2015, 6(2): 1090-1100.
[20] Tu K, Li C, Zheng X, et al. Prognostic significance of miR-218 in human hepatocellular carcinoma and its role in cell growth[J]. Oncol Rep, 2014, 32(4): 1571-1577.
[21] Feng Y, Wang L, Zeng J, et al. FoxM1 is overexpressed in Helicobacter pylori-induced gastric carcinogenesis and is negatively regulated by miR-370[J]. Mol Cancer Res, 2013, 11(8): 834-844.
[22] Song IS, Jeong YJ, Jeong SH, et al. FOXM1-induced PRX3 regulates stemness and survival of colon cancer cells via maintenance of mitochondrial function[J]. Gastroenterology, 2015, 149(4): 1006-1016.
[23] Gu C, Yang Y, Sompallae R, et al. FOXM1 is a therapeutic target for high-risk multiple myeloma[J]. Leukemia, 2016, 30(4): 873-882.
[24] Inoguchi S, Seki N, Chiyomaru T, et al. Tumour-suppressive microRNA-24-1 inhibits cancer cell proliferation through targeting FOXM1 in bladder cancer[J]. FEBS Lett, 2014, 588(17): 3170-3179.
[1] 张智慧,王丽丽,高华,张健,李娟,李远,武春晓,卢志明. 肺腺癌中缺氧诱导因子-1α调控程序性死亡因子配体1的表达[J]. 山东大学学报(医学版), 2017, 55(4): 65-70.
[2] 李学玲, 董西林, 岳英. 二甲双胍抑制裸鼠肺腺癌移植瘤生长的实验研究[J]. 山东大学学报(医学版), 2014, 52(S1): 1-2.
[3] 孙杰,牟晓燕,董雪丽. 舒尼替尼与吉西他滨联合及序贯应用对K-RAS突变A549细胞的影响[J]. 山东大学学报(医学版), 2014, 52(3): 45-49.
[4] 董雪丽,牟晓燕,刘庆亮,孙杰. 塞来昔布联合厄罗替尼对人肺癌裸鼠移植瘤生长及血管生成的影响[J]. 山东大学学报(医学版), 2013, 51(2): 49-52.
[5] 范恒建,张玉可,肖伟,张一,李海军,王得翔 . 肺腺癌患者外周血Treg和Th17细胞的变化及其对预后的影响[J]. 山东大学学报(医学版), 2012, 50(9): 73-78.
[6] 刘海荣1,于金明2,李岩1,梁婧1,刘晓琳1. ER、PR、C-erB-2与肺腺癌骨转移的相关性研究[J]. 山东大学学报(医学版), 2012, 50(4): 91-.
[7] 马育华1,2, 郑燕3,郏雁飞3,汪运山3. EGFR与DEC1蛋白共表达促进肺腺癌肿瘤细胞淋巴结转移[J]. 山东大学学报(医学版), 2012, 50(3): 24-28.
[8] 李海军,肖伟. 肺腺癌患者外周血Th17细胞比例变化及临床意义[J]. 山东大学学报(医学版), 2011, 49(8): 108-112.
[9] 吕怡静,任敏,王博,葛汝青,张继东. EZH2和CTGF在肺腺癌中的表达和意义[J]. 山东大学学报(医学版), 2011, 49(5): 94-97.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!