干扰MT1-MMP表达对口腔鳞癌细胞增殖、侵袭的影响

口腔生物医学 ›› 2022, Vol. 13 ›› Issue (3): 160-164.

干扰MT1-MMP表达对口腔鳞癌细胞增殖、侵袭的影响

肖涛¹,郝峰瑶²,郑政³,谢狄亚³,王志勇¹

1. 南京大学医学院附属口腔医院（南京市口腔医院）
2. 南京大学医学院附属口腔医院南京市口腔医院口腔颌面外科
3. 南京大学医学院附属口腔医院

收稿日期:2022-07-14 修回日期:2022-08-16 出版日期:2022-09-25 发布日期:2022-09-29
通讯作者: 王志勇 E-mail:wangzhiyong67@163.com
基金资助:
江苏省重点研发计划专项资金项目

Effects of MT1-MMP interference on the proliferation and invasive ability of oral squamous cell carcinoma

Received:2022-07-14 Revised:2022-08-16 Online:2022-09-25 Published:2022-09-29

摘要/Abstract

摘要： 目的：检测膜型基质金属蛋白酶-1（MT1-MMP）在口腔鳞癌（OSCC）中的表达，探讨其对OSCC细胞增殖、侵袭的影响。方法：选取40例OSCC及癌旁组织样本，实时荧光定量PCR检测样本中MT1-MMP及上皮细胞钙黏蛋白（E-cadherin）mRNA表达。采用小干扰RNA（siRNA）靶向干扰HSC3细胞MT1-MMP基因，实验分为siControl、siMT1-MMP、siControl+转化生长因子-β1（TGF-β1）及siMT1-MMP+TGF-β1组。采用CCK-8法检测细胞增殖，Transwell实验检测细胞侵袭能力，Western blot检测MT1-MMP、E-cadherin、TGF-β信号通路相关蛋白CUTL1及Wnt5a的表达。结果：相对于癌旁组织，OSCC组织中MT1-MMP mRNA水平为高表达，E-cadherin为低表达（P<0.05）；在干扰MT1-MMP表达后，HSC3细胞的增殖能力无明显变化（P＞0.05）；与siControl和siMT1-MMP组比较，siControl＋TGF-β1组和siMT1-MMP＋TGF-β1组细胞侵袭能力增强（P<0.01）；与siControl＋TGF-β1组比较，siMT1-MMP＋TGF-β1组细胞侵袭能力减弱（P<0.01）；与siControl组相比，siControl+TGF-β1组中MT1-MMP表达及TGF-β信号通路相关蛋白CUTL1及Wnt5a表达显著升高，E-cadherin表达下降（P<0.01）；与siControl+TGF-β1组相比，siMT1-MMP+TGF-β1组中MT1-MMP、CUTL1及Wnt5a的蛋白表达水平有所下调，且E-cadherin蛋白表达水平升高（P<0.05）。结论：干扰MT1-MMP可能通过调节TGF-β1诱导的EMT进程抑制OSCC细胞侵袭。

关键词: 口腔鳞癌, 膜型基质金属蛋白酶-1, 上皮细胞钙黏蛋白, 上皮间充质转化

Abstract: Objective: To detect the expression of membrane type 1 matrix metalloproteinase (MT1-MMP) in oral squamous cell carcinoma (OSCC) and its role on the proliferation and invasive ability of OSCC. Methods: RT-PCR was used to detect the expression of MT1-MMP and E-cadherin in OSCC and adjacent tissues; Small interfering RNA (siRNA) was used in targeted interference MT1-MMP gene in HSC3 cells. The experiment was divided into four groups: siControl group, siMT1-MMP group, siControl+transforming growth factor β1 (TGF-β1) group, siMT1-MMP+TGF-β1 group. CCK-8 method was used to detect cell proliferation of HSC3. Transwell assay was used to detect the invasive ability of cells. The expression of MT1-MMP, E-cadherin, TGF-β signaling pathway related proteins (CUTL1 and Wnt5a) was detected by Western blot. Results: Compared with the adjacent tissues, higher expression of MT1-MMP and lower expression of E-cadherin was exhibited in OSCC（P<0.05）; the cell proliferation of HSC3 cells did not change significantly after MT1-MMP interference（P＞0.05）; compared with siControl group and siMT1-MMP group, the HSC3 cell invasion number in siControl+TGF-β1 group and siMT1-MMP+TGF-β1 group was increased significantly; compared with siControl+TGF-β1 group, the HSC3 cell invasion number in siMT1-MMP+TGF-β1 group was decreased significantly（P<0.01）; compared with siControl group, protein expression of MT1-MMP, CUTL1 and Wnt5a increased significantly in siControl+TGF-β1 group, while the expression of E-cadherin decreased（P<0.01）; compared with siControl+TGF-β1 group, protein expression of MT1-MMP, CUTL1 and Wnt5a decreased partially in siMT1-MMP+TGF-β1 group, while the expression of E-cadherin increased significantly（P<0.05）. Conclusions: MT1-MMP interference may inhibit the invasion of OSCC through regulating the EMT process induced by TGF-β1.

Key words: oral squamous cell carcinoma, membrane type 1 matrix metalloproteinase, E-cadherin, epithelial-mesenchymal transition

肖涛郝峰瑶郑政谢狄亚王志勇. 干扰MT1-MMP表达对口腔鳞癌细胞增殖、侵袭的影响[J]. 口腔生物医学, 2022, 13(3): 160-164.

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