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 (TSP50), an oncogene overexpressed in breast cancer, can promote proliferation, migration, and invasion of breast cancer cells. Mechanistic studies have revealed that TSP50 promoted tumorigenesis mainly by activating NF-kappa B (NF-κB) and inhibiting activin signaling pathway, indicating that TSP50 played a critical role in the occurrence and development of breast cancer. However, there are few reports on the regulation of TSP50 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 TSP50 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 TSP50 mRNA 3′UTR and significantly inhibit the expression of TSP50 protein. Moreover, the effects of miR-4709-3p on the proliferation of breast cancer cells and mammary epithelial cells were detected in vitro. 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 in vivo 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 TSP50. 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.

中文翻译：

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miR-4709-3p 通过下调乳腺癌细胞中 TSP50 的表达来抑制细胞增殖

乳腺癌是全球女性身心健康的严重威胁。我们之前的研究结果表明，丝氨酸蛋白酶 50 ( TSP50 ) 是一种在乳腺癌中过表达的癌基因，可以促进乳腺癌细胞的增殖、迁移和侵袭。机制研究表明，TSP50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TSP50在乳腺癌的发生发展中起关键作用。然而，关于TSP50的规定的报道很少在乳腺癌中的表达。MicroRNAs (miRNAs) 已成为基因表达中必不可少的转录后调节因子，它们在乳腺癌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 预测和分析可以靶向TSP50 mRNA 3'UTR 的 miRNA，并发现了 6 个 miRNA。定量实时 PCR (qRT-PCR) 和蛋白质印迹的结果表明 miR-4709-3p 可以与TSP50 mRNA 3'UTR结合并显着抑制TSP50蛋白的表达。此外，体外检测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 抑制剂的过表达显着促进了乳腺上皮细胞的增殖。此外，还测试了miR-4709-3p对体内乳腺癌细胞致瘤性的影响，结果表明miR-4709-3p显着降低了裸鼠体内肿瘤的体积和重量。所有这些结果表明 miR-4709-3p 可以通过靶向TSP50抑制乳腺癌细胞的肿瘤发生。最后，研究了潜在的分子机制，我们发现 NF-κB 和激活素信号都参与了 miR-4709-3p 相关的肿瘤抑制作用。