Effects of knockdown of Stat5 on invasion and epithelial mesenchymal transition of thyroid carcinoma TT cells

doi:10.3760/cma.j.issn.1673-422X.2018.01.001

Abstract

Abstract: ObjectiveTo investigate the effects of knockdown of signal transducer and activator of transcription 5 (Stat5) on invasion and epithelial mesenchymal transition (EMT) of thyroid carcinoma TT cells. MethodsThyroid carcinoma TT cells were cultured and divided into Stat5small interfering RNA (siRNA) group and NCsiRNA group, transfected with Stat5 siRNA and negative control NCsiRNA respectively. After transfection, the numbers of invasive cells were determined by Transwell model and the expressions of matrix metalloproteinase (MMP) family genes, EMT marker genes, angiogenesis genes in the cells were determined by fluorescent quantitative PCR. ResultsThe numbers of invasive cells in Stat5siRNA group were significantly lower than those in NCsiRNA group (42.39±5.82 vs. 64.41±8.49, t＝-4.784, P=0.001; 51.23±6.38 vs. 78.54±9.52, t＝-5.329, P＜0.001; 60.35±8.35 vs. 98.42±11.25, t＝-6.076, P＜0.001) after the transfection of siRNA for 12 hours, 18 hours and 24 hours. Twentyfour hours after transfection of siRNA, the mRNA expressions of MMP1, MMP2, MMP9, MMP13, Ncadherin, Vimentin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin (Ang)1 and Ang2 in Stat5siRNA group were significantly lower than those in NCsiRNA group (0.42±0.07 vs. 1.03±0.15, t＝-8.240, P＜0.001; 0.35±0.06 vs. 1.01±0.13, t＝-10.307, P＜0.001; 0.29±0.05 vs. 1.05±0.18, t＝-9.097, P＜0.001; 0.54±0.08 vs. 0.98±0.12, t＝-6.822, P＜0.001; 0.38±0.06 vs. 1.04±0.18, t＝-7.778, P＜0.001; 0.29±0.04 vs. 1.06±0.12, t＝-12.612, P＜0.001; 0.36±0.07 vs. 1.06±0.14, t＝-10.000, P＜0.001; 0.43±0.08 vs. 0.97±0.12, t＝-8.372, P＜0.001; 0.25±0.03 vs. 1.03±0.12, t＝-14.100, P＜0.001; 0.19±0.03 vs. 0.99±0.13, t＝-13.408, P＜0.001). The mRNA expression of Ecadherin was significantly higher than that in NCsiRNA group (2.88±0.42 vs. 0.98±0.12, t＝9.726, P＜0.001). ConclusionKnockdown of Stat5 inhibits the invasion and EMT of thyroid carcinoma TT cells.

Key words: Thyroid neoplasms, Neoplasm invasiveness, Signal transducer and activator of transcription 5, Epithelial mesenchymal transition

Li Yan, Chen Qiongxia, Wang Xuming. Effects of knockdown of Stat5 on invasion and epithelial mesenchymal transition of thyroid carcinoma TT cells[J]. Journal of International Oncology, 2018, 45(1): 1-.

References

［1］ Glomski K, Nose V, Faquin WC, et al. Metastatic follicular thyroid carcinoma and the primary thyroid gross examination: institutional review of cases from 1990 to 2015［J］. Endocr Pathol, 2017, 28(2): 177185. DOI: 10.1007/s1202201794836. ［2］ Lee SE, Hwang TS, Choi YL, et al. Molecular profiling of papillary thyroid carcinoma in Korea with a high prevalence of BRAFV600E mutation［J］. Thyroid, 2017, 27(6): 802810. DOI: 10.1089/thy.2016.0547. ［3］薛翔, 刘红梅, 邵旦兵, 等. JAK/STAT信号通路调节机制的研究进展［J］. 现代生物医学进展, 2015, 15(11): 21612165. DOI: 10.13241/j.cnki.pmb.2015.11.045. ［4］ Kim C, Baek SH, Um JY, et al. Resveratrol attenuates constitutive STAT3 and STAT5 activation through induction of PTP epsilon and SHP2 tyrosine phosphatases and potentiates sorafenibinduced apoptosis in renal cell carcinoma［J］. BMC Nephrol, 2016, 17(17): 19. DOI: 10.1186/s1288201602337. ［5］ Li HX, Zhao W, Shi Y, et al. Retinoic acid amide inhibits JAK/STAT pathway in lung cancer which leads to apoptosis［J］. Tumour Biol, 2015, 36(11): 86718678. DOI: 10.1007/s1327701535348. ［6］ elemetjev S, Doric I, Paunovic I, et al. Coexpressed high levels of VEGFC and active MMP9 are associated with lymphatic spreading and local invasiveness of papillary thyroid carcinoma［J］. Am J Clin Pathol, 2016, 146(5): 594602. DOI: 10.1093/ajcp/aqw184. ［7］ Kalhori V, Trnquist K. MMP2 and MMP9 participate in S1Pinduced invasion of follicular ML1 thyroid cancer cells［J］. Mol Cell Endocrinol, 2015, 404: 113122. DOI: 10.1016/j.mce.2015.01.037. ［8］ Ding X, Yang DR, Xia L, et al. Targeting TR4 nuclear receptor suppresses prostate cancer invasion via reduction of infiltrating macrophages with alteration of the TIMP1/MMP2/MMP9 signals［J］. Mol Cancer, 2015, 14: 16. DOI: 10.1186/s1294301402811. ［9］ Wang JR, Li XH, Gao XJ, et al. Expression of MMP13 is associated with invasion and metastasis of papillary thyroid carcinoma［J］. Eur Rev Med Pharmacol Sci, 2013, 17(4): 427435. ［10］ Mitchell B, Dhingra JK, Mahalingam M. BRAF and epithelialmesenchymal transition: lessons from papillary thyroid carcinoma and primary cutaneous melanoma［J］. Adv Anat Pathol, 2016, 23(4): 244271. DOI: 10.1097/PAP.0000000000000113. ［11］ Baquero P, JimenezMora E, Santos A, et al. TGFβ induces epithelialmesenchymal transition of thyroid cancer cells by both the BRAF/MEK/ERK and Src/FAK pathways［J］. Mol Carcinog, 2016, 55(11): 16391654. DOI: 10.1002/mc.22415. ［12］ Ivanova K, Ananiev J, Aleksandrova E, et al. Expression of Ecadherin/betacatenin in epithelial carcinomas of the thyroid gland［J］. Open Access Maced J Med Sci, 2017, 5(2): 155159. DOI: 10.3889/oamjms.2017.043. ［13］ Da CX, Wu KX, Yue C, et al. Ncadherin promotes thyroid tumorigenesis through modulating major signaling pathways［J］. Oncotarget, 2017, 8(5): 81318142. DOI: 10.18632/oncotarget.14101. ［14］ Calangiu CM, Simionescu CE, Stepan AE, et al. The expression of CK19, vimentin and Ecadherin in differentiated thyroid carcinomas［J］. Rom J Morphol Embryol, 2014, 55(3): 919925. ［15］ Gulubova M, Ivanova K, Ananiev J, et al. VEGF expression, microvessel density and dendritic cell decrease in thyroid cancer［J］. Biotechnol Biotechnol Equip, 2014, 28(3): 508517. DOI: 10.1080/13102818.2014.909151. ［16］ Chen ZY. Establishing the relationship between FGF/MV and FI/FD, and determining the saturation state of sevoflurane anaesthesia during the induction phase and factors affecting nonrespiratory tract ejection volum［J］. J Int Med Res, 2013, 41(3): 785794. DOI: 10.1177/0300060513477575. ［17］ Davis PJ, Sudha T, Lin HY, et al. Thyroid hormone, hormone analogs, and angiogenesis［J］. Compr Physiol, 2016, 6(1): 353362. DOI: 10.1002/cphy.c150011.

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