Osteoglycin regulates proliferation and invasion of papillary thyroid carcinoma cells via NF2/Hippo signaling pathway
Objective To explore the role and its regulatory mechanism of osteoglycin(OGN)in papillary thyroid carcinoma(PTC).Methods The expression of OGN and the disease-free survival time in thyroid cancer patients were analyzed using gene expression profile interactive analysis(GEPIA)database.OGN expression in 52 cases of PTC tissues and adjacent normal tissues from our hospital was detected by real-time quantitative PCR and Western blotting.OGN expression in PTC cell lines(K1,TPC-1,IHH-4,KTC-1 and BCPAP)and normal thyroid cell line(Nthy-ori3-1)was also analyzed by real-time quantitative PCR and Western blotting.TPC-1 and KTC-1 cells were divided into control group,pc-NC group(transfected with pcDNA3.1 empty plasmid)and pc-OGN group(transfected with pcDNA3.1-OGN plasmid).Then,TPC-1 cells were co-transfected with pcDNA3.1-OGN plasmid and si-RNA-NF2 or pcDNA3.1-OGN plasmid and si-RNA-LATS1,respectively,namely pc-NC group,pc-OGN group,pc-OGN+si-NF2 group and pc-OGN+si-LATS1 group.Cell proliferation,apoptosis,invasion and migration were detected by CCK-8,flow cytometry,Transwell and wound healing assays,respectively.The protein expressions of epithelial mesenchymal transition related proteins(E-cadherin,N-cadherin,Vimentin),NF2 and key proteins in Hippo signaling[Yes associated protein 1(YAP1),mammalian STE20-like protein kinase(MST1)and large tumor suppressor 1(LATS1)]were detected by Western blotting.Results GEPIA database analysis showed that OGN expression in tumor tissues was significantly lower than that in normal tissues(P＜0.01),and low OGN expression level was closely correlated with shorter disease-free survival time.OGN expression in tumor tissues was significantly lower than that in adjacent normal tissues(P＜0.01).Compared with Nthy-ori3-1 cells,OGN mRNA and protein expression levels in PTC cell lines were decreased to varying degrees(P＜0.01).Compared with pc-NC group,cell proliferation,invasion and migration ability of TPC-1 and KTC-1 cells were significantly inhibited in pc-OGN group(P＜0.01),and N-cadherin and Vimentin protein expressions were decreased(P＜0.01),while the apoptosis rate and E-cadherin expression were significantly increased(P＜0.01).Compared with pc-NC group,NF2 expression level and MST1 and LAST1 phosphorylation levels were increased,while YAP1 phosphorylation level was decreased in pc-OGN group(P＜0.01).Compared with pc-OGN group,the apoptosis rate was significantly inhibited in pc-OGN+si-NF2 group and pc-OGN+si-LATS1 group(P＜0.01),while the cell invasion and migration abilities were significantly promoted(P＜0.01).Conclusion OGN can inhibit the cell proliferation,and the invasion and migration abilities,and promote the cell apoptosis via NF2/Hippo signaling pathway.OGN is expected to be a targeted intervention site for PTC.
万方数据
维普
