Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin 300070, China.
J Biol Chem. 2012 Apr 20;287(17):14301-9. doi: 10.1074/jbc.M111.337642. Epub 2012 Mar 7.
MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. In this study, we demonstrate that miR-214 is frequently down-regulated in cervical cancer, and its expression reduces the proliferation, migration, and invasiveness of cervical cancer cells, whereas inhibiting its expression results in enhanced proliferation, migration, and invasion. miR-214 binds to the 3'-UTR of UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7), thereby repressing GALNT7 expression. Furthermore, we are the first to show, using quantitative real-time PCR, that GALNT7 is frequently up-regulated in cervical cancer. The knockdown of GALNT7 markedly inhibits cervical cancer cell proliferation, migration, and invasion, whereas ectopic expression of GALNT7 significantly enhances these properties, indicating that GALNT7 might function as an oncogene in cervical cancer. The restoration of GALNT7 expression can counteract the effect of miR-214 on cell proliferation, migration, and invasiveness of cervical cancer cells. Together, these results indicate that miR-214 is a new regulator of GALNT7, and both miR-214 and GALNT7 play important roles in the pathogenesis of cervical cancer.
微小 RNA 是一类小的非编码 RNA,作为基因表达的关键调节剂,在转录后水平发挥作用。在这项研究中,我们证明 miR-214 在宫颈癌中经常下调,其表达降低了宫颈癌细胞的增殖、迁移和侵袭能力,而抑制其表达则导致增殖、迁移和侵袭能力增强。miR-214 与 UDP-N-乙酰-α-D-半乳糖胺:多肽 N-乙酰半乳糖胺基转移酶 7(GALNT7)的 3'UTR 结合,从而抑制 GALNT7 的表达。此外,我们首次通过定量实时 PCR 显示,GALNT7 在宫颈癌中经常上调。GALNT7 的敲低显著抑制宫颈癌细胞的增殖、迁移和侵袭,而 GALNT7 的异位表达则显著增强这些特性,表明 GALNT7 可能在宫颈癌中作为癌基因发挥作用。GALNT7 表达的恢复可以抵消 miR-214 对宫颈癌细胞增殖、迁移和侵袭的影响。综上所述,这些结果表明 miR-214 是 GALNT7 的一个新调节因子,miR-214 和 GALNT7 都在宫颈癌的发病机制中发挥重要作用。