Down-regulation of MALAT1 inhibits cervical cancer cell invasion and metastasis by inhibition of epithelial-mesenchymal transition
Down-regulation of MALAT1 inhibits cervical cancer cell invasion and metastasis by inhibition of epithelial-mesenchymal transition
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DOI：
10.1039/c5mb00685f
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Li, Guancheng
中科院分区：
文献类型：
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作者：
Sun, Ruili;Qin, Changfei;Li, Guancheng
转移相关肺腺癌转录本1（MALAT 1）是长链非编码RNA（lncRNA）家族的成员，在多种肿瘤中高度富集，是肿瘤转移标志物和预后因子。在这项研究中，我们发现MALAT 1的表达水平在宫颈癌（CC）细胞和组织中显着增加。在CC细胞中通过shRNA下调MALAT 1的表达，可抑制CC细胞的侵袭和转移。基因芯片分析显示，MALAT 1基因敲除后，上皮细胞标志物E-cadherin和ZO-1表达上调，间充质细胞标志物beta-catenin和Vimentin表达下调。随后的RT-PCR、免疫印迹和免疫荧光结果进一步证实了这种调控。同时，转录因子snail，其功能是调节上皮间质转化（EMT），也下调了转录和蛋白水平的MALAT 1下调。此外，我们通过基因芯片分析发现，MALAT 1表达水平与宫颈上皮组织中HPV感染呈正相关。这些结果提示MALAT 1通过诱导EMT促进宫颈癌的侵袭和转移，可能成为宫颈癌预防和治疗的靶点。
The metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a member of the long non-coding RNA (lncRNA) family, has been reported to be highly enriched in many kinds of cancers and to be a metastasis marker and a prognostic factor. In this study, we found that MALAT1 expression levels were significantly increased in cervical cancer (CC) cells and tissues. The down-regulation of MALAT1 by shRNA in CC cells inhibited the invasion and metastasis in vitro and in vivo. Microarray analysis showed that the knockdown of MALAT1 up-regulated the epithelial markers E-cadherin and ZO-1, and down-regulated the mesenchymal markers beta-catenin and Vimentin. This regulation was further confirmed by subsequent observation from RT-PCR, western blot, and immunofluorescence results. Meanwhile, the transcription factor snail, which functions to modulate epithelial-mesenchymal transition (EMT), was also down-regulated at both transcript and protein levels by MALAT1 down-regulation. In addition, we found that MALAT1 expression levels were positively related to HPV infection in cervical epithelial tissues by microarray analysis. Taken together, these results suggest that MALAT1 functions to promote cervical cancer invasion and metastasis via induction of EMT, and it may be a target for the prevention and therapy of cervical cancers.