[1]周秦毅,陈隽,冯嘉麟,等.TM7SF4对人甲状腺乳头状癌细胞IHH-4 增殖、凋亡和侵袭的作用研究[J].国际内分泌代谢杂志,2016,36(04):241-246.[doi:10.3760/cma.j.issn.1673-4157.2016.04.08]
　Zhou Qinyi,Chen Jun,Feng Jialin,et al.Effects of TM7SF4 on proliferation, apoptosis and invasion of human papillary thyroid cancer IHH-4 cells[J].International Journal of Endocrinology and Metabolism,2016,36(04):241-246.[doi:10.3760/cma.j.issn.1673-4157.2016.04.08]
点击复制

TM7SF4对人甲状腺乳头状癌细胞IHH-4 增殖、凋亡和侵袭的作用研究()
分享到：

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
36
期数:
2016年04期
页码:
241-246
栏目:
论著
出版日期:
2016-07-20

文章信息/Info

Title:
Effects of TM7SF4 on proliferation, apoptosis and invasion of human papillary thyroid cancer IHH-4 cells
作者:
周秦毅; 陈隽; 冯嘉麟; 王家东
200001 上海交通大学医学院附属仁济医院头颈外科
Author(s):
Zhou Qinyi;  Chen Jun;  Feng Jialin;  Wang Jiadong
Department of Head and Neck Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200001, China
关键词:
甲状腺乳头状癌;  树突表达特异性7跨膜蛋白;  细胞增殖;  细胞凋亡;  细胞侵袭
Keywords:
Papillary thyroid cancer;  Dendrocyte expressed seven transmembrane protein;  Cell proliferation;  Cell apoptosis;  Cell invasion
DOI:
10.3760/cma.j.issn.1673-4157.2016.04.08
摘要:
目的 探讨树突表达特异性7跨膜蛋白(TM7SF4)的低表达对人甲状腺乳头状癌细胞IHH-4增殖、凋亡和侵袭的作用及其相关机制。方法 选取甲状腺乳头状癌患者的手术标本(癌组织及癌旁组织)及甲状腺乳头状癌细胞系IHH-4为对象。qRT-PCR法检测病理组织和细胞系IHH-4中TM7SF4的mRNA表达量。分别用MTT法、流式细胞分析和Transwell法检测TM7SF4表达量对IHH-4细胞增殖、凋亡和侵袭的影响。Western印迹检测IHH-4细胞中磷酸化与非磷酸化磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)、哺乳动物雷帕酶素靶蛋白(mTOR)的表达。结果 与癌旁组织相比,甲状腺癌组织中TM7SF4的mRNA表达水平显著升高(t=52.31,P<0.05)。与正常甲状腺细胞系Nthy-ori 3-1相比,IHH-4细胞系中TM7SF4的表达水平也显著上升(t=34.35,P<0.05)。与对照组细胞相比,沉默TM7SF4的表达后,可诱导IHH-4细胞凋亡,而细胞增殖和侵袭能力受到显著抑制(F=8.32,7.55,846.40; P均<0.05)。此外,沉默TM7SF4的表达后可显著降低磷酸化PI3K、磷酸化Akt、磷酸化mTORmRNA及蛋白的表达(F=1 014.88,1 121.29,985.22,720.14,854.63,4 563.12; P均<0.05)。结论 低表达的TM7SF4可能通过下调PI3K/Akt/mTOR通路而抑制IHH-4细胞增殖、诱导凋亡并抑制侵袭。
Abstract:
Objective To investigate the effects and mechanisms of dendrocyte expressed seven transmembrane protein(TM7SF4)on proliferation, apoptosis and invasion of human papillary thyroid cancer(PTC)cell IHH-4. Methods PTC tumor tissues and the adjacent normal tissues, as well as the human PTC IHH-4 cells were used in this study. TM7SF4 mRNA in tissues and in IHH-4 cells were analyzed using qRT-PCR analysis. The effects of TM7SF4 on proliferation, apoptosis and invasion of IHH-4 cells were analyzed using MTT assay, flow cytometry and Transwell assay, respectively. Furthermore, Western blotting was used to detect the expression of TM7SF4,phosphorylated and non-phosphorylated phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin(mTOR)protein. Results Compared with adjacent normal tissues, TM7SF4 mRNA and protein were significantly increased IHH-4 in PTC tissues(t=52.31, P<0.05). TM7SF4 was also significantly increased in cells compared with that in Nthy-ori 3-1 cells(t=34.35, P<0.05). Consequently, silencing TM7SF4 significantlyinduced IHH-4 cells apoptosis, inhibited proliferation and suppressed invasion compared with controls(F=8.32, 7.55, 846.40; all P<0.05). Moreover, the mRNA and protein levels of phosphorylated-PI3K, phosphorylated-Akt and phosphorylated-mTOR were significantly decreased by silencing TM7SF4(F=1 014.88,1 121.29,985.22,720.14,854.63,4 563.12, all P<0.05). Conclusion Down-regulated TM7SF4 may be an inhibitor of PTC development and metastasis through suppressing PI3K/Akt/mTOR pathway.

参考文献/References:

[1] Cho BY, Choi HS, Park YJ, et al. Changes in the clinicopathological characteristics and outcomes of thyroid cancer in Korea over the past four decades[J].Thyroid,2013,23(7):797-804. DOI: 10.1089/thy.2012.0329.
[2] McLeod DS, Cooper DS, Ladenson PW,et al. Prognosis of differentiated thyroid cancer in relation to serum thyrotropin and thyroglobulin antibody status at time of diagnosis[J].Thyroid,2014,24(1):35-42. DOI: 10.1089/thy.2013.0062.
[3] Sacks W, Braunstein GD. Papillary thyroid carcinoma∥Braunstein GD, eds. Thyroid Cancer[M]. Springer, 2012: 133-153.
[4] Wójcicka A, Czetwertyńska M, wierniak M,et al. Variants in the ATM-CHEK2-BRCA1 axis determine genetic predisposition and clinical presentation of papillary thyroid carcinoma[J].Genes Chromosomes Cancer,2014,53(6):516-523. DOI: 10.1002/gcc.22162.
[5] Hay ID, Lee RA, Davidge-Pitts C,et al. Long-term outcome of ultrasound-guided percutaneous ethanol ablation of selected "recurrent" neck nodalmetastases in 25 patients with TNM stages Ⅲ or ⅣA papillary thyroid carcinoma previously treated by surgeryand 131I therapy[J].Surgery,2013,154(6):1448-1454; discussion 1454-1455. DOI: 10.1016/j.surg.2013.07.007.
[6] Beauregard M, Gagnon E, Guay-Bélanger S,et al. Identification of rare genetic variants in novel loci associated with Paget's disease of bone[J].Hum Genet,2014,133(6):755-768.DOI: 10.1007/s00439-013-1409-x.
[7] Chiu YH, Mensah KA, Schwarz EM,et al. Regulation of human osteoclast development by dendritic cell-specific transmembrane protein(DC-STAMP)[J].J Bone Miner Res,2012,27(1):79-92. DOI: 10.1002/jbmr.531.
[8] Zeng Z, Zhang C, Chen J. Lentivirus-mediated RNA interference of DC-STAMP expression inhibits the fusion and resorptive activity of human osteoclasts[J].J Bone Miner Metab,2013,31(4):409-416. DOI: 10.1007/s00774-013-0434-0.
[9] Kim HS, Kim DH, Kim JY, et al. Microarray analysis of papillary thyroid cancers in Korean[J].Korean J Intern Med,2010,25(4):399-407. DOI: 10.3904/kjim.2010.25.4.399.
[10] Nikolova DN, Zembutsu H, Sechanov T,et al. Genome-wide gene expression profiles of thyroid carcinoma: Identification of molecular targets for treatment of thyroid carcinoma[J].Oncol Rep,2008,20(1):105-121.
[11] Lan X, Zhang H, Wang Z, et al. Genome-wide analysis of long noncoding RNA expression profile in papillary thyroid carcinoma[J].Gene,2015,569(1):109-117. DOI: 10.1016/j.gene.2015.05.046.
[12] Hoelting T, Siperstein AE, Clark OH,et al. Epidermal growth factor enhances proliferation, migration, and invasion of follicular and papillary thyroid cancer in vitro and in vivo[J].J Clin Endocrinol Metab,1994,79(2):401-408.
[13] Basolo F, Pollina L, Fontanini G,et al. Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression[J].Br J Cancer,1997,75(4):537-541.
[14] Rivera M, Ricarte-Filho J, Knauf J, et al. Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes(encapsulated vs infiltrative)reveals distinct BRAF and RAS mutation patterns[J].Mod Pathol,2010,23(9):1191-1200. DOI: 10.1038/modpathol.2010.112.
[15] Matsubara R, Kukita T, Ichigi Y,et al. Characterization and identification of subpopulations of mononuclear preosteoclasts induced by TNF-α in combination with TGF-β in rats[J].PLoS One,2012,7(10):e47930. DOI: 10.1371/journal.pone.0047930.
[16] Herbert BA, Valerio MS, Gaestel M, et al. Sexual dimorphism in MAPK-activated protein kinase-2(MK2)regulation of RANKL-induced osteoclastogenesis in osteoclast progenitor subpopulations[J].PLoS One,2015,10(5):e0125387. DOI: 10.1371/journal.pone.0125387.
[17] Tu SM, Som A, Tu B,et al. Effect of Paget's disease of bone(osteitis deformans)on the progression of prostate cancer bone metastasis[J].Br J Cancer,2012,107(4):646-651.DOI: 10.1038/bjc.2012.315.
[18] Janku F, Tsimberidou AM, Garrido-Laguna I,et al. PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors[J].Mol Cancer Ther,2011,10(3):558-565. DOI: 10.1158/1535-7163.MCT-10-0994.
[19] Yap TA, Garrett MD, Walton MI,et al. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises[J].Curr Opin Pharmacol,2008,8(4):393-412. DOI: 10.1016/j.coph.2008.08.004.
[20] Slomovitz BM, Coleman RL. The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer[J].Clin Cancer Res,2012,18(21):5856-5864. DOI: 10.1158/1078-0432.CCR-12-0662.
[21] Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations[J].Nat Rev Cancer,2009,9(8):550-562. DOI: 10.1038/nrc2664.
[22] Wan X, Helman LJ. The biology behind mTOR inhibition in sarcoma[J].Oncologist,2007,12(8):1007-1018.
[23] Santarpia L, El-Naggar AK, Cote GJ,et al. Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer[J].J Clin Endocrinol Metab,2008,93(1):278-284.
[24] Miyakawa M, Tsushima T, Murakami H,et al. Increased expression of phosphorylated p70S6 kinase and Akt in papillary thyroid cancer tissues[J].Endocr J,2003,50(1):77-83.

相似文献/References:

[1]于亚静,杨彩哲,刘明,等.BRAFV600E在甲状腺乳头状癌与桥本甲状腺炎相关性中的研究[J].国际内分泌代谢杂志,2014,(06):375.[doi:10.3760/cma.j.issn.1673-4157.2014.06.004]
　Yu Yajing,Yang Caizhe,Liu ming,et al.Study of BRAFV600E in the correlation between papillary thyroid carcinoma and Hashimoto’s thyroiditis[J].International Journal of Endocrinology and Metabolism,2014,(04):375.[doi:10.3760/cma.j.issn.1673-4157.2014.06.004]
[2]党红转,徐书杭,王建华,等.颈部淋巴结转移与甲状腺乳头状癌的治疗及预后[J].国际内分泌代谢杂志,2016,36(04):277.[doi:10.3760/cma.j.issn.1673-4157.2016.04.16]
　Dang Hongzhuan*,Xu Shuhang,Wang Jianhua,et al.Treatment and prognosis of papillary thyroid cancer with cervical lymph node metastasis[J].International Journal of Endocrinology and Metabolism,2016,36(04):277.[doi:10.3760/cma.j.issn.1673-4157.2016.04.16]
[3]徐婷,吴丹,胡翠宁,等.甲状腺乳头状癌的淋巴结转移预测模型建立[J].国际内分泌代谢杂志,2021,41(06):596.[doi:10.3760/cma.j.cn121383-20200826-08042]
　Xu Ting,Wu Dan,Hu Cuining,et al.Construction of a risk-scoring model to predict lymph node metastasis in papillary thyroid carcinoma[J].International Journal of Endocrinology and Metabolism,2021,41(04):596.[doi:10.3760/cma.j.cn121383-20200826-08042]
[4]周美岑,兰玲,邓微,等.MCPIP4诱导甲状腺乳头状癌细胞系TPC-1周期停滞的机制[J].国际内分泌代谢杂志,2023,43(02):86.[doi:10.3760/cma.j.cn121383-20210605-06008]
　Zhou Meicen,Lan Ling,Deng Wei,et al.The mechanism of RNA binding protein MCPIP4 induces cell cycle arrest in papillary thyroid cancer[J].International Journal of Endocrinology and Metabolism,2023,43(04):86.[doi:10.3760/cma.j.cn121383-20210605-06008]

备注/Memo

备注/Memo:
通信作者:王家东,Email: drjiadongw@aliyun.com
更新日期/Last Update: 2016-09-20