National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.
Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, China.
DNA Cell Biol. 2021 Jul;40(7):969-978. doi: 10.1089/dna.2020.6260. Epub 2021 May 5.
Breast cancer is a serious threat to the physical and mental health of women all over the world. Our previous results have shown that Serine protease 50 (), an oncogene overexpressed in breast cancer, can promote proliferation, migration, and invasion of breast cancer cells. Mechanistic studies have revealed that promoted tumorigenesis mainly by activating NF-kappa B (NF-κB) and inhibiting activin signaling pathway, indicating that played a critical role in the occurrence and development of breast cancer. However, there are few reports on the regulation of expression in breast cancer. MicroRNAs (miRNAs) have emerged as an essential posttranscriptional regulator in gene expression and they played a significant role in breast cancer regulation. In the present study, bioinformatics software miRBase and TargetScan were first used to predict and analyze miRNAs that could target mRNA 3'UTR and six miRNAs were found. Results from quantitative real-time PCR (qRT-PCR) and western blot suggested that miR-4709-3p could bind to mRNA 3'UTR and significantly inhibit the expression of protein. Moreover, the effects of miR-4709-3p on the proliferation of breast cancer cells and mammary epithelial cells were detected . Our data suggested that overexpression of miR-4709-3p mimic greatly inhibited the proliferation of breast cancer cells, whereas overexpression of miR-4709-3p inhibitors significantly promoted the proliferation of breast epithelial cells. Furthermore, the effect of miR-4709-3p on the tumorigenicity of breast cancer cells was tested, and the results showed that miR-4709-3p significantly reduced the volume and weight of tumor in nude mice. All these results suggested that miR-4709-3p could inhibit the tumorigenesis of breast cancer cells by targeting . Finally, the underlying molecular mechanisms were investigated and we found that both NF-κB and activin signaling were involved in miR-4709-3p-related tumor inhibitory effect.
乳腺癌是全世界女性身心健康的严重威胁。我们之前的研究结果表明，在乳腺癌中过表达的丝氨酸蛋白酶 50 () 是一种致癌基因，它可以促进乳腺癌细胞的增殖、迁移和侵袭。机制研究表明，主要通过激活 NF-κB (NF-κB) 和抑制激活素信号通路促进肿瘤发生，表明在乳腺癌的发生和发展中发挥着关键作用。然而，关于乳腺癌中 表达的调控报道较少。microRNAs (miRNAs) 已成为基因表达的重要转录后调节因子，它们在乳腺癌的调控中发挥着重要作用。在本研究中，首先使用生物信息学软件 miRBase 和 TargetScan 预测和分析可能靶向 mRNA 3'UTR 的 miRNAs，发现了 6 个 miRNAs。实时定量 PCR (qRT-PCR) 和 Western blot 结果表明，miR-4709-3p 可以与 mRNA 3'UTR 结合并显著抑制 蛋白的表达。此外，还检测了 miR-4709-3p 对乳腺癌细胞和乳腺上皮细胞增殖的影响。我们的数据表明，miR-4709-3p 模拟物的过表达极大地抑制了乳腺癌细胞的增殖，而 miR-4709-3p 抑制剂的过表达则显著促进了乳腺上皮细胞的增殖。此外，还检测了 miR-4709-3p 对乳腺癌细胞致瘤性的影响，结果表明 miR-4709-3p 显著降低了裸鼠肿瘤的体积和重量。所有这些结果表明，miR-4709-3p 可以通过靶向 抑制乳腺癌细胞的肿瘤发生。最后，还研究了潜在的分子机制，发现 NF-κB 和激活素信号通路均参与了 miR-4709-3p 相关的肿瘤抑制作用。
