IL-6通过诱导lncTCF7表达促进甲状腺乳头状癌TPC-1细胞上皮-间充质转化、迁移和侵袭
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摘要
目的:探讨白细胞介素6(IL-6)通过诱导长链非编码RNA lnc TCF7表达对人甲状腺乳头状癌TPC-1细胞上皮-间充质转化(EMT)、迁移和侵袭能力的影响。方法:以0、5、10、20和50μg/L的IL-6作用于TPC-1细胞24 h或以50μg/L的IL-6作用于TPC-1细胞0、6、12和24 h后,RT-qPCR检测IL-6对TPC-1细胞中lnc TCF7表达的影响。以50μg/L的IL-6处理TPC-1细胞24 h后,Western blot检测IL-6对TPC-1细胞中E-cadherin和vim-entin蛋白表达的影响。建立lnc TCF7过表达的TPC-1细胞株,Western blot和Transwell小室实验检测过表达lnc TCF7对TPC-1细胞EMT、迁移和侵袭能力的影响。敲减lnc TCF7的表达并给予50μg/L的IL-6处理后,观察lnc TCF7对IL-6处理后的TPC-1细胞EMT、迁移和侵袭能力的影响。结果:IL-6可呈剂量和时间依赖性地诱导TPC-1细胞中lnc TCF7的表达(P <0.05)。过表达lnc TCF7可下调TPC-1细胞中E-cadherin表达,上调vimentin表达,增强细胞的迁移和侵袭能力(P <0.05)。IL-6可使TPC-1细胞中E-cadherin表达降低,vimentin、Snail和Slug表达升高,同时,增强细胞的迁移和侵袭能力,增大细胞间隙;敲减lnc TCF7表达能够明显抑制IL-6引起的上述变化。结论:IL-6可通过诱导lnc TCF7表达促进甲状腺乳头状癌TPC-1细胞的EMT、迁移和侵袭。
AIM:To investigate the effect of interleukin-6(IL-6)on epithelial-mesenchymal transition(EMT),migration and invasion of papillary thyroid carcinoma TPC-1 cells by inducing the expression of long noncoding RNA lnc TCF7.METHODS:The effects of IL-6 on the expression of lnc TCF7 in the TPC-1 cells were detected by RT-q PCR after the TPC-1 cells were treated with IL-6 at 0,5,10,20 and 50μg/L for 24 h or with IL-6 at 50μg/L for 0,6,12 and 24 h.After the TPC-1 cells were treated with IL-6 at 50μg/L for 24 h,the effect of IL-6 on the protein expression of E-cadherin and vimentin in the TPC-1 cells was detected by Western blot.The TPC-1 cell line with lnc TCF7 over-expression was established,and the effects of lnc TCF7 over-expression on EMT,migration and invasion of the TPC-1 cells were measured by Western blot and Transwell assay.After knockdown of lnc TCF7 expression and exposure to IL-6 at 50μg/L,the effects of lnc TCF7 on EMT,migration and invasion of TPC-1 cells treated with IL-6 were observed.RESULTS:The expression of lnc TCF7 in the TPC-1 cells was induced by IL-6 in a dose-and time-dependent manner.The expression of E-cadherin was down-regulated,the expression of vimentin was up-regulated,and the migration and invasion abilities of the TPC-1 cells were enhanced by lnc TCF7 over-expression(P<0.05).The expression of E-cadherin was decreased,the expression of vimentin,Snail and Slug was increased,and the migration and invasion abilities of the TPC-1 cells and intercellular space were enhanced by IL-6.The above changes induced by IL-6 were significantly inhibited by knockdown of lnc TCF7expression.CONCLUSION:IL-6 promotes the EMT,migration and invasion of papillary thyroid carcinoma TPC-1 cells by inducing the expression of lnc TCF7.
AIM:To investigate the effect of interleukin-6(IL-6)on epithelial-mesenchymal transition(EMT),migration and invasion of papillary thyroid carcinoma TPC-1 cells by inducing the expression of long noncoding RNA lnc TCF7.METHODS:The effects of IL-6 on the expression of lnc TCF7 in the TPC-1 cells were detected by RT-q PCR after the TPC-1 cells were treated with IL-6 at 0,5,10,20 and 50μg/L for 24 h or with IL-6 at 50μg/L for 0,6,12 and 24 h.After the TPC-1 cells were treated with IL-6 at 50μg/L for 24 h,the effect of IL-6 on the protein expression of E-cadherin and vimentin in the TPC-1 cells was detected by Western blot.The TPC-1 cell line with lnc TCF7 over-expression was established,and the effects of lnc TCF7 over-expression on EMT,migration and invasion of the TPC-1 cells were measured by Western blot and Transwell assay.After knockdown of lnc TCF7 expression and exposure to IL-6 at 50μg/L,the effects of lnc TCF7 on EMT,migration and invasion of TPC-1 cells treated with IL-6 were observed.RESULTS:The expression of lnc TCF7 in the TPC-1 cells was induced by IL-6 in a dose-and time-dependent manner.The expression of E-cadherin was down-regulated,the expression of vimentin was up-regulated,and the migration and invasion abilities of the TPC-1 cells were enhanced by lnc TCF7 over-expression(P<0.05).The expression of E-cadherin was decreased,the expression of vimentin,Snail and Slug was increased,and the migration and invasion abilities of the TPC-1 cells and intercellular space were enhanced by IL-6.The above changes induced by IL-6 were significantly inhibited by knockdown of lnc TCF7expression.CONCLUSION:IL-6 promotes the EMT,migration and invasion of papillary thyroid carcinoma TPC-1 cells by inducing the expression of lnc TCF7.
引文
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[9]郑仁东,张会峰,曹琳,等.白细胞介素6对未分化型甲状腺癌肿瘤干细胞增殖的影响[J].中华内分泌代谢杂志,2016,32(10):851-856.
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[12]车祺,刘素英,董曦.白细胞介素6与子宫内膜癌侵袭和转移的相关性分析[J].中国临床医学,2018,25(1):52-55.
[13]Chen W,Xia T,Wang D,et al.Human astrocytes secrete IL-6 to promote glioma migration and invasion through upregulation of cytomembrane MMP14[J].Oncotarget,2016,7(38):62425-62438.
[14]Wu X,Pan T,Quan Z,et al.IL-6 secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and metastasis of gastric cancer via JAK2/STAT3signaling pathway[J].Oncotarget,2017,8(13):20741-20750.
[15]Zou M,Zhang X,Xu C.IL6-induced metastasis modulators p-STAT3,MMP-2 and MMP-9 are targets of 3,3’-diindolylmethane in ovarian cancer cells[J].Cell Oncol(Dordr),2015,39(1):47-57.
[16]Wang Y,He L,Du Y,et al.The long noncoding RNAlnc TCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling[J].Cell Stem Cell,2015,16(4):413-425.
[17]Gao X,Guo X,Xue H,et al.lnc TCF7 is a negative prognostic factor,and knockdown of lnc TCF7 inhibits migration,proliferation and tumorigenicity in glioma[J].Sci Reports,2017,7(1):17456-17466.
[18]孙振华,赵志泓,蒋华平,等.肿瘤微环境相关因子IL-6、IL-10、CXCR7在甲状腺乳头状癌中的表达及临床意义[J].中国普通外科杂志,2017,26(5):578-582.
[19]Beksac K,Sonmez C,Cetin B,et al.Evaluation of proinflammatory cytokine and neopterin levels in women with papillary thyroid carcinoma[J].Int J Biol Markers,2016,31(4):e446-e450.
[20]Tang ZN,Wang YC,Liu XX,et al.An immunohistochemical study of CTHRC1,vimentin,E-cadherin expression in papillary thyroid carcinoma[J].J Clin Otorhinolaryngol Head Neck Surg,2018,32(8):595-598.
[21]Lei H,Gao Y,Xu X.LncRNA TUG1 influences papillary thyroid cancer cell proliferation,migration and EMT formation through targeting miR-145[J].Acta Biochim Biophys Sin(Shanghai),2017,49(7):588-597.
[2]曾俊,董丹丹,李芳华.白细胞介素6在结直肠癌中的表达及其与增殖细胞核抗原表达的相关性[J].中华病理学杂志,2017,46(2):112-113.
[3]Shang GS,Liu L,Qin YW.IL-6 and TNF-αpromote metastasis of lung cancer by inducing epithelial-mesenchymal transition[J].Oncol Lett,2017,13(6):4657-4660.
[4]胡金华,张耀晴,艾瑞华,等.分化型甲状腺癌患者血清TNF-α、IL-6和VEGF表达与侵袭转移的相关性分析[J].现代肿瘤医学,2015,23(6):771-774.
[5]何雨歆,周雨秋,李超,等.甲状腺乳头状癌淋巴管特性及转移机制研究进展[J].肿瘤预防与治疗,2016,29(2):81-85.
[6]Li T,Li T,Zhu J,et al.Long non-coding RNA lnc TCF7activates the Wnt/β-catenin pathway to promote metastasis and invasion in colorectal cancer[J].Oncol Lett,2017,14(6):7384-7390.
[7]Wu J,Wang D.Long noncoding RNA TCF7 promotes invasiveness and self-renewal of human non-small cell lung cancer cells[J].Hum Cell,2017,30(1):23-29.
[8]Wu J,Zhang J,Shen B,et al.Long noncoding RNAlnc TCF7,induced by IL-6/STAT3 transactivation,promotes hepatocellular carcinoma aggressiveness through epithelial-mesenchymal transition[J].J Exp Clin Cancer Res,2015,34(1):116-125.
[9]郑仁东,张会峰,曹琳,等.白细胞介素6对未分化型甲状腺癌肿瘤干细胞增殖的影响[J].中华内分泌代谢杂志,2016,32(10):851-856.
[10]Ataie-Kachoie P,Pourgholami MH,Morris DL.Inhibition of the IL-6 signaling pathway:a strategy to combat chronic inflammatory diseases and cancer[J].Cytokine Growth Factor Rev,2013,24(2):163-173.
[11]唐甜,安东建,曹建国.癌症中IL-6信号通路研究进展[J].现代肿瘤医学,2016,24(9):1470-1472.
[12]车祺,刘素英,董曦.白细胞介素6与子宫内膜癌侵袭和转移的相关性分析[J].中国临床医学,2018,25(1):52-55.
[13]Chen W,Xia T,Wang D,et al.Human astrocytes secrete IL-6 to promote glioma migration and invasion through upregulation of cytomembrane MMP14[J].Oncotarget,2016,7(38):62425-62438.
[14]Wu X,Pan T,Quan Z,et al.IL-6 secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and metastasis of gastric cancer via JAK2/STAT3signaling pathway[J].Oncotarget,2017,8(13):20741-20750.
[15]Zou M,Zhang X,Xu C.IL6-induced metastasis modulators p-STAT3,MMP-2 and MMP-9 are targets of 3,3’-diindolylmethane in ovarian cancer cells[J].Cell Oncol(Dordr),2015,39(1):47-57.
[16]Wang Y,He L,Du Y,et al.The long noncoding RNAlnc TCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling[J].Cell Stem Cell,2015,16(4):413-425.
[17]Gao X,Guo X,Xue H,et al.lnc TCF7 is a negative prognostic factor,and knockdown of lnc TCF7 inhibits migration,proliferation and tumorigenicity in glioma[J].Sci Reports,2017,7(1):17456-17466.
[18]孙振华,赵志泓,蒋华平,等.肿瘤微环境相关因子IL-6、IL-10、CXCR7在甲状腺乳头状癌中的表达及临床意义[J].中国普通外科杂志,2017,26(5):578-582.
[19]Beksac K,Sonmez C,Cetin B,et al.Evaluation of proinflammatory cytokine and neopterin levels in women with papillary thyroid carcinoma[J].Int J Biol Markers,2016,31(4):e446-e450.
[20]Tang ZN,Wang YC,Liu XX,et al.An immunohistochemical study of CTHRC1,vimentin,E-cadherin expression in papillary thyroid carcinoma[J].J Clin Otorhinolaryngol Head Neck Surg,2018,32(8):595-598.
[21]Lei H,Gao Y,Xu X.LncRNA TUG1 influences papillary thyroid cancer cell proliferation,migration and EMT formation through targeting miR-145[J].Acta Biochim Biophys Sin(Shanghai),2017,49(7):588-597.