| Thyroid cancer is the most common endocrine tumor.The differentiated thyroid carcinoma has a high survival rate,but undifferentiated thyroid cancer has a very poor prognosis.And the undifferentiated cancer is derived from highly differentiated cancer,but the mechanism of dedifferentiation of highly differentiated cancer is still unclear.PDLIM7,a cytoskeleton binding protein,is involved in the development and maintenance of a variety of tissues,and generally plays a pro-cancer factor in the occurrence and development of tumors.PDLIM7 can promote the development of thyroid papillary carcinoma,but its role and mechanism in the dedifferentiation process of thyroid highly differentiated carcinoma remain to be further investigated.ObjectiveTo clarify the expression difference of PDLIM7 in thyroid cancer and non-cancer thyroid tissue,to analyze the effect of PDLIM7 on the biological behavior of thyroid cancer cells,and to explore the role of PDLIM7 in the process of thyroid cancer dedifferentiation and its possible mechanism.Methods1.The expression of PDLIM7 protein in thyroid cancer and paracancerous non-cancerous thyroid tissues was detected by immunohistochemistry and Western Blot.The correlation between the expression of PDLIM7 protein and the clinicopathological features of thyroid cancer was analyzed.2.The expression of PDLIM7 protein in different thyroid cancer cell lines and immortalized thyroid epithelial cell lines was measured by Western Blot and q RT PCR.3.The expression of PDLIM7 in K1,KTC-1 and TPC-1 cells was down-regulated by lentivirus.4.The effects of knockdown of PDLIM7 on proliferation,colony formation,migration and invasion of thyroid cells were investigated by CCK-8,plate cloning,scratching,and Transwell migration and invasion experiments.5.The effect of knockdown of PDLIM7 on proliferation and invasion of thyroid cells in vivo was investigated by subcutaneous and caudal vein tumor-formation experiments in nude mice.6.The effect of downregulating PDLIM7 on transcription of thyroid cancer cells was analyzed by the next generation sequencingResults1.The expression of PDLIM7 was up-regulated in papillary thyroid carcinoma tissues compared with paracancerous non-cancerous thyroid tissues,and its up-regulated expression was correlated with tumor size,lymph node metastasis,distant metastasis and other pathological features.However,compared with papillary thyroid carcinoma,PDLIM7 expression was down-regulated in poorly differentiated thyroid carcinoma.2.PDLIM7 was high-expressed in thyroid immortified epithelial cell line Nthy-ori-3-1 and thyroid papillary carcinoma cell line K1 and KTC-1,and the expression in K1 and KTC-1 was higher than that in Nthy-ori I-3-1 cells.PDLIM7 was low-expressed in thyroid papillary carcinoma cell line TPC-1 and B-CPAP and the expression which was lower than that in Nthy-ori-3-1 cell line.The expression was absent in poorly differentiated thyroid cancer cell line WRO.3.In vitro cell experiments showed that knockdown of PDLIM7 promoted the proliferation,migration and invasion of K1 cells,but inhibits the proliferation,migration and invasion of KTC-1 and TPC-1 cells.4.In nude mouse xenograft,knockdown of PDLIM7 promoted the growth of xenograft of K1 cells,but inhabited the growth of xenograft of TPC-1 cells.5.Transcriptome analysis showed that down-regulation of PDLIM7 inhibited the enrichment of PI3K-Akt and JAK-STAT signaling pathways in KTC-1 and TPC-1 cells,and down-regulation of PDLIM7 promoted the enrichment of focal adhesion and cell adhesion molecules in K1 cells.Conclusion1.The expression of PDLIM7 was up-regulated in papillary thyroid carcinoma tissues and some papillary thyroid cancer cells(K1 and KTC-1),while down-regulated in poorly differentiated thyroid carcinoma tissues and poorly differentiated thyroid cancer cells(WRO).It is suggested that PDLIM7 may have a bidirectional effect of promoting and inhibiting cancer.2.In different papillary thyroid cancer cells,PDLIM7 exerts two completely different biological behavior effects of tumor promotion and tumor inhibition,and regulates different signaling pathways,which may be dependent on the different genetic backgrounds of the above-mentioned thyroid cancer cells.3.Combined with the expression data of clinical tissue specimens,cells and functional experiments in vitro,it is suggested that PDLIM7 has a two-way effect in papillary thyroid carcinoma: it may play a pro-cancer role in the process of occurrence,while it may play a anti-cancer role in the process of malignant progression,and the relevant mechanism needs to be further clarified. |
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