The Role And Molecular Mechanism Of CHIA In The Initiation And Development Of Thyroid Cancer

Objective: The incidence of thyroid cancer(Thyroid cancer,TC)is increasing year by year,and the incidence tends to be younger,but its specific pathogenesis is still unclear.Mammalian acid chitinase(CHIA)—a member of the 18 glycosylation hydrolase family,expressed in stomach,lung,and thyroid tissues,can degrade chitin-containing pathogens and participate in parasite host defense responses.In the thyroid,studies have shown that the upregulation of chitinase-3-like protein 1(CHI3L1)can promote the progression of thyroid cancer.In addition,the role of chitinase-like protein in tumors has become a research hotspot in the field of medicine recently.However,the expression and function of its family homologue CHIA in thyroid cancer are still unclear.Therefore,this study focused on exploring the expression of CHIA in thyroid cancer tissues and cells,analyzing its correlation with clinicopathological features,and preliminarily clarifying the molecular mechanism of CHIA up-regulation in the pathogenesis of thyroid cancer combined with cell function experiments.In order to find a new theoretical and scientific basis for diagnosis and treatment of thyroid cancer.Methods: 1.Detection of CHIA expression in thyroid cancer and adjacent tissues by immunohistochemistry;the expression of CHIA in human normal thyroid cells Nthori-3-1 and human thyroid cancer cells(BCPAP;TPC-1;KTC-1;FTC133 and8305C)was detected by WB technique;2.Analyze the correlation between the expression of CHIA and the clinicopathological information of patients(Including:gender,age,tumor size,TNM stage and pathological stage,etc.);3.Stable transfection of thyroid cancer cells with silencing and overexpression of CHIA lentivirus were constructed respectively,and the transfection efficiency was verified by WB;4.Cell function experiments to explore the effect of CHIA silencing or overexpression on the apoptosis,proliferation,invasion and migration of thyroid cancer cells;5.The effects of silencing or overexpression of CHIA on EMT,proliferation,apoptosis and other related proteins of thyroid cancer cells were detected by WB;6.To explore whether CHIA plays a role in the happening and developmenting of thyroid cancer through the STAT3 pathway.Results: 1.The expression of CHIA was significantly up-regulated in thyroid cancer tissues(the difference was statistically significant);2.Silencing of CHIA in thyroid cancer cells TPC-1 could induce apoptosis and inhibit the proliferation and migration of thyroid cancer cells;Consistent results were obtained by reverse verification of overexpression of CHIA in KTC-1;3.Silencing of CHIA inhibited the expression of proliferation markers(C-myc,Cyclin D1)and EMT markers(mesenchymal-associated proteins Vim,Snail)in thyroid cancer cells,and promote the expression of epithelium-associated proteins(E-cadherin,ZO-1et.);However,after overexpression of CHIA in KTC-1 cells,C-myc,Cyclin D1,Vim,Snail were up-regulated,while ZO-1and E-cadherin were down-regulated;4.In TPC-1 cells,the expression of JAK2,STAT3 and P-STAT3 was down-regulated after down-regulation of CHIA;But when overexpression of CHIA in KTC-1 cells,STAT3 and P-STAT3 are up-regulated.Conclusion: 1.This study showed that the expression of CHIA gene was significantly up-regulated in thyroid cancer and correlated with gender and tumor size.The expression of CHIA was higher in female patients and patients with tumor size greater than 2 cm.2.Further mechanism research and analysis showed that CHIA can promote the proliferation and migration of TPC-1 cells and KTC-1 cells through the JAK2/STAT3 pathway,and inhibit their apoptosis,suggesting that the acidic mammalian chitinase CHIA may provide new insights for the diagnosis and treatment of TC.