| 蒯 榕,徐 莹,褚以忞,周 璐,张海芹,李 吉.m6A RNA甲基转移酶METTL3对肠癌细胞上皮间质转化及侵袭能力的影响[J].,2021,(21):4019-4023 |
| m6A RNA甲基转移酶METTL3对肠癌细胞上皮间质转化及侵袭能力的影响 |
| The Role of METTL3 in the EMT and Invasion Ability in Colorectal Cancer Cells |
| 投稿时间：2021-02-24 修订日期：2021-03-21 |
| DOI：10.13241/j.cnki.pmb.2021.21.004 |
| 中文关键词: METTL3 上皮间质转化 转移 TGFβ |
| 英文关键词: METTL3 EMT Metastasis TGFβ |
| 基金项目:上海交通大学医工（理）交叉基金项目（ZH2018QNB24）；上海市长宁区科学技术委员会一般项目（CNKW2018Y02) |
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| 中文摘要: |
| 摘要 目的：探讨METTL3对肠癌细胞上皮间质转化及侵袭能力的影响。方法：TGFβ诱导肠癌细胞HCT116和SW480发生上皮间质转化；细胞划痕实验和Transwell-Matrigeal穿膜试验分别检测细胞转移侵袭能力；实时荧光定量PCR检测靶基因转录水平；siRNA干扰技术敲减肠癌细胞METTL3水平。结果：细胞划痕修复实验表明：TGFβ诱导组相对愈合面积与对照组相比显著增大（P<0.0001），而TGFβ+敲减METTL3联合组处理组相对愈合面积与TGFβ诱导组相比显著减少（P<0.0001）。Transwell-Matrigeal细胞穿膜试验表明：TGFβ诱导组穿膜细胞数较对照组细胞显著增多（P<0.0001），而TGFβ+敲减METTL3联合组处理组与TGFβ诱导组相比显著减少。TGFβ诱导组可显著诱导肠癌细胞发生上皮间充质转化，即增加核心转录因子Snail1和ZEB1水平，减低CDH1及上调Vimentin（VIM）水平，METTL3表达随TGFβ处理时间逐步上调。TGFβ+敲减METTL3联合组较TGFβ诱导组ZEB1和Snail1转录水平显著减低。结论：METTL3在TGFβ介导肠癌细胞EMT中起到关键作用，敲减METTL3可削弱肠癌细胞转移和侵袭能力，靶向抑制METTL3可能成为干预结直肠转移的重要分子靶点。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the impact of METTL3 on EMT and invasion ability in colorectal cancer cells. Methods: TGFβ was used to induce EMT in HCT116 and SW480 cells. Wound scratch assay and Transwell-matrigeal assay were used to evaluate the invasion ability of CRC cells. qPCR was used to measure the expression of target genes. SiRNAs were used to knockdown METTL3 in CRC cells. Results: The healing area in the TGFβ treated cells was larger than control cells（P<0.0001）, while TGFβ plus METTL3 knockdown groups cells showed smaller healing area than TGFβ treated cells（P<0.0001）. Transwell-Matrigeal showed the penetrated cells in the TGFβ treated cells was more than control cells（P<0.0001）, while TGFβ plus METTL3 knockdown groups cells showed less penetrated cells than TGFβ treated cells（P<0.0001）. TGFβ treatment induced EMT, while expression of snail1, ZEB1, VIM and METTL3 was up-regulated and CHD1 was down-regulated. TGFβ plus METTL3 knockdown groups cells showed less expression of snail1 and ZEB1 than TGFβ treated cells. Conclusion: METTL3 plays key role in the TGFβ induced EMT. Knockdown of METTL3 can impair TGFβ's effect, which provides novel target for blocking metastasis in CRC. |
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