摘要
目的:揭示肽P11对人分化型甲状腺癌细胞生长和转移的影响,以及肽P11与miRNA-126表达之间的关联。方法:采用qRT-PCR分别检测30份乳头状甲状腺癌和滤泡性甲状腺癌组织及配对癌旁组织中miR-126的表达。分别应用miR-126模拟物转染TPC-1和FTC-133细胞系。应用500μmol·L^(-1)的肽P11培养两种甲状腺癌细胞24 h。采用MTT法测定细胞活力,膜联蛋白V(Annexin V)-FITC/碘化丙啶(PI)测定法检测细胞凋亡,伤口愈合实验检测细胞迁移,Transwell小室侵袭实验检测细胞侵袭,Western blot检测脂蛋白受体相关蛋白6(LRP6)及Wnt/β-catenin信号通路下游基因MMP-7、c-Myc和cyclin D1的表达。结果:miR-126在分化型甲状腺癌组织和细胞系中表达下调(P<0.05),并且miR-126的异常表达与TNM分期和淋巴结转移相关(P<0.05)。肽P11处理显著上调了分化型甲状腺癌细胞中miR-126的表达(P<0.05)。肽P11处理和miR-126的过表达均抑制了分化型甲状腺癌细胞的增殖、迁移和侵袭,并诱导细胞凋亡(P<0.05)。肽P11处理和miR-126的过表达下调了细胞中LRP6、MMP-7、c-Myc和cyclin D1的表达(P<0.05)。结论:肽P11可通过上调分化型甲状腺癌细胞中miR-126的表达来发挥抗癌作用。miR-126可能是乳头状甲状腺癌治疗的潜在靶标,而肽P11可通过靶向miR-126来发挥抗癌作用。
Objective:To discuss the effect of peptide P11 on the growth and metastasis of human differentiated thyroid cancer cells,and the relationship between peptide P11 and miRNA-126 expression.Methods:qRT-PCR was used to detect the expression of miR-126 in 30 papillary thyroid carcinoma and follicular thyroid carcinoma tissues and matched paracancerous tissues.The TCR-1 and FTC-133 cell lines were transfected with miR-126 mimics,respectively.Two kinds of thyroid cancer cells were cultured for 24 h with 500μmol·L^(-1)peptide P11.Cell viability was determined by MTT assay,apoptosis was detected by Annexin V-FITC/propidium iodide(PI)assay,cell migration was detected by wound healing assay,cell invasion was detected by Transwell chamber invasion assay,and expression of lipoprotein receptor-associated protein 6(LRP6)and downstream genes of Wnt/β-catenin signaling pathways MMP-7,c-Myc and cyclin D1 was detected by Western blot.Results:The expression of miR-126 was down-regulated in differentiated thyroid carcinoma tissues and cell lines(P<0.05),and the abnormal expression of miR-126 was associated with TNM staging and lymph node metastasis(P<0.05).Peptide P11 treatment significantly up regulated the expression of miR-126 in differentiated thyroid cancer cells(P<0.05).Peptide P11 treatment and overexpression of miR-126 inhibited proliferation,migration and invasion and induced apoptosis of differentiated thyroid cancer cells(P<0.05).Peptide P11 treatment and overexpression of miR-126 down regulated the expression of LRP6,MMP-7,c-Myc and cyclin D1 in cells(P<0.05).Conclusion:Peptide P11 can exert anti-cancer effect by up-regulating the expression of miR-126 in differentiated thyroid cancer cells.miR-126 may be a potential target for PTC treatment,while peptide P11 can exert anticancer effects by targeting miR-126.
作者
边芳
李宁
李奇
BIAN Fang;LI Ning;LI Qi(Department of Endocrinology,Shaanxi Friendship Hospital,Xi'an 710068,China;Department of Oncology,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Department of Neurologic Sursery,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)
出处
《现代医学》
2021年第8期833-840,共8页
Modern Medical Journal
基金
陕西省重点研发计划项目(2019SF-152)
作者简介
边芳(1978),女,陕西西安人,副主任医师。E-mail:BianJess@163.com;通信作者:李奇,E-mail:26928959@qq.com
