TGF-β1信号通路相关的microRNA在唾液腺腺样囊性癌侵袭转移中的作用

中国口腔颌面外科杂志 ›› 2014, Vol. 12 ›› Issue (4): 301-306.

TGF-β1信号通路相关的microRNA在唾液腺腺样囊性癌侵袭转移中的作用

梁衍灿¹, 宇文婷¹, 梁启祥¹, 谢宏亮², 徐志英³, 万荻¹, 张彬¹

1.中山大学孙逸仙纪念医院口腔颌面外科,广东广州 510120;
2.深圳市第一人民医院口腔科,广东深圳 518000;
3.北京大学深圳医院口腔科,广东深圳 518000

收稿日期:2013-12-26 出版日期:2014-07-10 发布日期:2014-08-20
通讯作者: 张彬,Tel：020-81332429,E-mail：13682263011@126.com
作者简介:梁衍灿(1984- ),男,硕士,住院医师,E-mail：yancan214@163.com
基金资助:
广东省自然科学基金( 9151008901000041); 广东省科技计划国际合作项目 (2010B050700005); 广东省科技计划项目(2012B031800029)

TGF-β1 signaling pathway related microRNA regulates metastasis of salivary adenoid cystic carcinoma

LIANG Yan-can¹, YU Wen-ting¹, LIANG Qi-Xiang¹, XIE Hong-liang², XU Zhi-ying³, WAN Di¹, ZHANG Bin

1.Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University. Guangzhou 510120;
2. Department of Stomatology, People’s Hospital of Shenzhen. Shenzhen 518000;
3.Department of Stomatology, Shenzhen Hospital of Peking University. Shenzhen 518000, Guangdong Province, China

Received:2013-12-26 Online:2014-07-10 Published:2014-08-20
Supported by:
Supported by Natural Science Foundation of Guangdong Province (9151008901000041), International Cooperation Project of Science and Technology Research Program of Guangdong Province (2010B050700005) and Science and Technology Planning Project of Guangdong Province (2012B031800029)

摘要/Abstract

摘要： 目的探讨TGF-β1/MAPKs/MMPs信号通路相关的microRNA (miRNA)在唾液腺腺样囊性癌(salivary adenoid cystic carcinoma, SACC)侵袭、转移中的作用。方法：采用 miRNA 芯片检测TGF-β1 刺激腺样囊性癌细胞（SACC-83、SACC-LM）前、后的miRNA表达谱;对 miRNA 表达谱进行差异分析;然后挑选几个显著差异表达的miRNA,采用实时荧光定量PCR（qRT-PCR）进一步加以验证,同时运用miRNA 靶基因预测软件预测其可能调控的靶基因。结果：芯片结果显示,与低转移株SACC-83相比,高转移株SACC-LM中的miRNA上调表达40个,下调表达 101个;经TGF-β1处理后,进一步显著上调的miRNA 1个,下调12个;qRT-PCR 验证结果与 miRNAs 芯片相符。对显著差异表达的miRNAs进行靶基因预测,共筛选出与 TGF-β1/MAPKs/MMPs信号通路相关的5个miRNAs（miR-125a-5p、miR-181d、mir-145-3p、mir-126-3p和mir-320d）,其对应的靶基因有P38(MAPK14)、MMP2、ERK1/2和SMADs。结论：不同转移能力的SACC存在差异表达的 miRNAs;TGF-β1能够影响SACC细胞miRNAs 的表达;miR-125a-5p、miR-34a、mir-145-3p、mir-126-3p和mir-195可能在SACC转移相关信号调节通路TGF-β1/MAPKs/MMPs中起着重要的调控作用。

关键词: 唾液腺, 腺样囊性癌, microRNA, TGF-β, 1, 侵袭, 转移

Abstract: PURPOSE: To illustrate the relationship between TGF-β1/MAPKs/MMPs signaling pathway and microRNA (miRNA) expression, and to explore the potential role of miRNA in the metastasis of salivary adenoid cystic carcinoma (SACC). METHODS: MiRNA array was performed to analyse the changes of miRNA expression inSACC cells before or after TGF-β1 stimulation, and then several significant different microRNAs were selected to be verified by qRT-PCR assay. Meanwhile, their target genes were predicted by miRNA target gene prediction programs. RESULTS: MicroRNA microassay showed that SACC_LM_neg/SACC_83_neg: up 40, down 101.One of them was up-regulated and twelve miRNAs of them were down- regulated after treated by TGF- β1 which were accordant with the results of qRT-PCR assay. MiR-125a-5p, miR-181d , mir-145-3p, mir-126-3p and mir-320d were chosen and several genes were predicted as targets of these differently regulated miRNAs related to TGF-β1/MAPKs/MMPs signaling pathway. CONCLUSION: There are differentially expressed microRNAs between SACC-LM and SACC-83. TGF-β1 can affect miRNAs profiling of SACC. MiR-125a-5p, miR-181d, mir-145-3p, mir-126-3p and mir-320d may be regulated by TGF-β1/MAPKs/MMPs signaling pathway.

Key words: Salivary gland, Adenoid cystic carcinoma, microRNA, TGF-β1, Invasion, Migration

中图分类号:

R739.8

梁衍灿, 宇文婷, 梁启祥, 谢宏亮, 徐志英, 万荻, 张彬. TGF-β1信号通路相关的microRNA在唾液腺腺样囊性癌侵袭转移中的作用[J]. 中国口腔颌面外科杂志, 2014, 12(4): 301-306.

LIANG Yan-can, YU Wen-ting, LIANG Qi-Xiang, XIE Hong-liang, XU Zhi-ying, WAN Di, ZHANG Bin. TGF-β1 signaling pathway related microRNA regulates metastasis of salivary adenoid cystic carcinoma[J]. China J Oral Maxillofac Surg, 2014, 12(4): 301-306.

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