肽P11通过上调miR-126表达抑制分化型甲状腺癌细胞增殖和侵袭-现代医学

肽P11通过上调miR-126表达抑制分化型甲状腺癌细胞增殖和侵袭

单位：1. 陕西省友谊医院内分泌科, 陕西西安 710068;
2. 西安交通大学第一附属医院肿瘤内科, 陕西西安 710061;
3. 西安交通大学第一附属医院神经外科, 陕西西安 710061

关键词：分化型甲状腺癌肽P11 miRNA-126 脂蛋白受体相关蛋白6 Wnt/β-catenin信号通路

分类号：R736.1

出版年·卷·期（页码）：2021·49·第八期（833-840）

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500 μmol·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 500 μmol·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.

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