干扰Mig-6基因表达对非小细胞肺癌EGFR信号通路的影响-东南大学学报医学版

干扰Mig-6基因表达对非小细胞肺癌EGFR信号通路的影响

单位：莱芜市人民医院呼吸内科, 山东莱芜 271100

分类号：R734.2;Q786

出版年·卷·期（页码）：2017·36·第三期（416-421）

摘要：

目的：探讨干扰丝裂原诱导因子-6（Mig-6）基因表达对非小细胞肺癌表皮生长因子受体（EGFR）信号通路的影响。方法：A549、H1650细胞系均分为阴性对照组（si-NC组）和阳性实验组（si-Mig-6组），si-Mig-6组采用特异性小干扰RNA （siRNA）干扰Mig-6表达，si-NC组仅加入不含质粒的空载体，转染后采用MTT法检测细胞增殖能力，检测各组细胞侵袭能力和EGFR、ERK、AKT的蛋白及mRNA表达水平。结果：siRNA转染72 h后，si-Mig-6组Mig-6 mRNA及蛋白表达均显著低于si-NC组（P<0.05），细胞增殖能力显著高于si-NC组，细胞侵袭能力亦显著高于si-NC组（P<0.05）。Mig-6对EGFR信号通路具有负向调控作用，干扰Mig-6表达，si-Mig-6组EGFR、细胞外调节蛋白激酶（ERK）、丝氨酸苏氨酸蛋白激酶（AKT）蛋白及mRNA表达均显著高于si-NC组（P<0.05）。结论：干扰Mig-6表达能够增强非小细胞肺癌增殖、侵袭能力，其可能通过对EGFR通路的负向调控而实现这一生物学功能，Mig-6有望成为治疗非小细胞肺癌一个潜在基因靶点。

Objective:To explore the effect of interfering Mig-6 gene expression on EGFR pathway in non small cell lung cancers. Methods:A549, H1650 cell lines were divided into negative control group(si-NC group)and the positive experimental group(si-Mig-6 group). The si-Mig-6 group was interfered by siRNA, while the Si-NC group was transfected with empty vector.After transfection, the cell proliferation and invasion ability and the expression of EGFR, ERK, AKT mRNA and protein were determined by MTT assay. Results:After 72 h of siRNA transfection, the expression of Mig-6 mRNA and protein in si-Mig-6 group was significantly lower than that in si-NC group(P<0.05). The cell proliferation and invasion ability in si-Mig-6 group were significantly higher than those in si-NC group(P<0.05). Mig-6 was negatively correlated with EGFR signaling pathway.When interfering Mig-6 expression,the expression of EGFR, ERK, AKT protein and mRNA in si-Mig-6 group were significantly higher than that in group si-NC group(P<0.05). Conclusion:Interference of Mig-6 expression can enhance proliferation and invasion ability in non small cell lung cancers,which may be related to negative regulation of EGFR pathway. Mig-6 is expected to become a potential gene therapy target for non-small cell lung cancers.

参考文献：

[1] 陈万青,张思维,邹小农,等.中国肺癌发病死亡的估计和流行趋势研究[J].中国肺癌杂志,2010,13(5):488-493.
[2] RYU J H,SHIN M,KIM S A,et al.In vivo fluorescence imaging for cancer diagnosis using receptor-targeted epidermal growth factor-based nanoprobe[J].Biomaterials,2013,34(36):9149-9159.
[3] SRIDHARAN V,SHARMA S K,MOROS E G,et al.Effects of radiation on the epidermal growth factor receptor pathway in the heart[J].Int J Radiat Biol,2013,89(7):539-547.
[4] MARUYAMA K,TAKEYAMA H,MORI T,et al.Detection of epidermal growth factor receptor(EGFR)mutations in non-small cell lung cancer(NSCLC)using a fully automated system with a nano-scale engineered biomagnetite[J].Biosens Bioelectron,2007,22(9-10):2282-2288.
[5] KIM T H,LEE D K,CHO S N,et al.Critical tumor suppressor function mediated by epithelial mig-6 in endometrial cancer[J].Cancer Res,2013,73(16):5090-5099.
[6] LI Z,DONG Q,WANG Y,et al.Downregulation of Mig-6 in nonsmall-cell lung cancer is associated with EGFR signaling[J].Mol Carcinog,2012,51(7):522-534.
[7] LI Z,QU L,ZHONG H,et al.Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2[J].Oncol Rep,2014,31(4):1707-1714.
[8] KIM T H,YOO J Y,KIM H I,et al.Mig-6 Suppresses endometrial cancer associated with pten deficiency and ERK activation[J].Cancer Res,2014,74(24):7371-7382.
[9] RESCHKE M,FERBY I,STEPNIAK E,et al.Mitogen-inducible gene-6 is a negative regulator of epidermal growth factor receptor signaling in hepatocytes and humanhepatocellular carcinoma[J].Hepatology,2010,51(4):1383-1390.
[10] LIN C I,BARLETTA J A,NEHS M A,et al.Thyroid-specific knockout of the tumor suppressor mitogen-inducible gene 6 activates epidermal growth factor receptor signaling pathways and suppresses nuclear factor-κB activity[J].Surgery,2011,150(6):1295-1302.
[11] 李紫璇,钟红珊,徐克,等.Mig-6通过负向调控EGFR通路抑制肺癌细胞增殖[J].现代肿瘤医学,2014,22(10):2259-2262.
[12] 李紫璇,翟欢,钟红珊,等.Mig-6基因表达对肝癌细胞增殖和凋亡的影响[J].现代肿瘤医学,2016,24(12):1857-1861.
[13] YOON Y K,KIM H P,SONG S H,et al.Down-regulation of mitogen-inducible gene 6,a negative regulator of EGFR,enhances resistance to MEK inhibition in KRAS mutant cancer cells[J].Cancer Lett,2012,316(1):77-84.
[14] RESCHKE M,FERBY I,STEPNIAK E,et al.Mitogen-inducible gene-6 is a negative regulator of epidermal growth factor receptor signaling in hepatocytes and human hepatocellular carcinoma[J].Hepatology,2010,51(4):1383-1390.
[15] RUAN D T,WARREN R S,MOALEM J,et al.Mitogen-inducible gene-6 expression correlates with survival and is an independent predictor of recurrence in BRAF(V600E)positive papillary thyroid cancers[J].Surgery,2008,144(6):908-913.
[16] WALSH A M,LAZZARA M J.Differential parsing of EGFR endocytic flux among parallel internalization pathways in lung cancer cells with EGFR-activating mutations[J].Integr Biol(Camb),2014,6(3):312-323.
[17] PARK S Y,CHOI H K,SEO J S,et al.DNAJB1 negatively regulates MIG6 to promote epidermal growth factor receptor signaling[J].Biochim Biophys Acta,2015,1853(10 Pt A):2722-2730.
[18] ZHANG Y W,STAAL B,SU Y,et al.Evidence that MIG-6 is a tumor-suppressor gene[J].Oncogene,2007,26(2):269-276.
[19] YING H,ZHENG H,SCOTT K,et al.Mig-6 controls EGFR trafficking and suppresses gliomagenesis[J].Proc Natl Acad Sci U S A,2010,107(15):6912-6917.
[20] LOMBARDI A,CANTINI G,MELLO T,et al.Molecular mechanisms underlying the pro-inflammatory synergistic effect of tumor necrosis factor alpha and interferon gamma in human microvascular endothelium[J].Eur J Cell Biol,2009,88(12):731-742.
[21] 朱静,陈小飞.食管癌分子靶向治疗研究进展[J].现代医学,2011,39(5):623-626.

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