Cripto-1 is highly expressed in many cancers, and downregulating its expression may become a promising approach for cancer treatment. However, the regulation of Cripto-1 expression is not well characterized. In this study, we focused on the post-transcriptional regulation of Cripto-1 expression and analyzed the potential miRNAs that bind to the 3′UTR of Cripto-1 mRNA. miR-3929 was found to be able to bind to the 3′UTR and downregulate the expression of Cripto-1 in cervical cancer cells. Then, we analyzed the effect of miR-3929 on the biological behavior of cervical cancer cells, finding that miR-3929 could reduce cell viability, DNA synthesis, and Ki67 expression and induce cell cycle arrest in the G2/M phase; overexpression of Cripto-1 reversed the inhibitory effect of miR-3929 on proliferation. Moreover, DAPI staining and flow cytometry revealed that miR-3929-induced cell apoptosis is dependent on the mitochondrial pathway; the overexpression of Cripto-1 reversed the proapoptotic effect of miR-3929. Finally, the in vivo results showed that miR-3929 significantly inhibits the growth of HeLa xenograft tumors in nude mice. Therefore, our findings suggest that miR-3929 inhibits the proliferation and induces the apoptosis of cervical cancer cells by downregulating Cripto-1 via specifically targeting the 3′UTR of its mRNA.
Cytogenet Genome Res

中文翻译：

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miR-3929 通过下调宫颈癌细胞中 Cripto-1 的表达来抑制增殖并促进细胞凋亡

Cripto-1 在许多癌症中高度表达，下调其表达可能成为一种很有前途的癌症治疗方法。然而，Cripto-1 表达的调节并没有得到很好的表征。在这项研究中，我们专注于 Cripto-1 表达的转录后调控，并分析了与 Cripto-1 mRNA 的 3'UTR 结合的潜在 miRNA。发现 miR-3929 能够与 3'UTR 结合并下调 Cripto-1 在宫颈癌细胞中的表达。然后，我们分析了 miR-3929 对宫颈癌细胞生物学行为的影响，发现 miR-3929 可以降低细胞活力、DNA 合成和 Ki67 表达，并诱导细胞周期停滞在 G2/M 期；Cripto-1 的过表达逆转了 miR-3929 对增殖的抑制作用。而且，DAPI 染色和流式细胞术显示 miR-3929 诱导的细胞凋亡依赖于线粒体途径；Cripto-1 的过表达逆转了 miR-3929 的促凋亡作用。最后，体内结果显示miR-3929显着抑制裸鼠HeLa异种移植瘤的生长。因此，我们的研究结果表明，miR-3929 通过特异性靶向其 mRNA 的 3'UTR 下调 Cripto-1，从而抑制宫颈癌细胞的增殖并诱导其凋亡。
细胞基因组研究