MicroRNA-24 upregulation inhibits proliferation, metastasis and induces apoptosis in bladder cancer cells by targeting CARMA3
MicroRNA-24 upregulation inhibits proliferation, metastasis and induces apoptosis in bladder cancer cells by targeting CARMA3
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DOI：
10.3892/ijo.2023.5515
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发表时间：
2015-10
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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越来越多的证据表明，microRNAs（miRNAs）的异常调控与人类肿瘤的进展和转移有关。先前的研究已经显示了miR-24在多种肿瘤中的失调。然而，miR-24在人类膀胱癌中的作用尚未得到很好的阐明。因此，我们研究miR-24在人膀胱癌细胞系中的生物学功能和分子机制，探讨其是否可能成为膀胱癌治疗的生物标志物。在我们的研究中，我们发现miR-24在人膀胱癌细胞系中下调。此外，低水平的miR-24与膀胱癌细胞中CARMA 3表达的增加相关。上调miR-24可显著抑制膀胱癌细胞的增殖、阻滞细胞周期并诱导细胞凋亡。此外，过表达miR-24抑制膀胱癌细胞的侵袭和上皮间质转化（EMT）。生物信息学分析预测CARMA 3是miR-24的潜在靶基因。通过荧光素酶报告基因检测进一步证实miR-24可以直接靶向CARMA 3。在用miR-24模拟物转染的膀胱癌细胞中过表达CARMA 3部分逆转了miR-24的抑制作用。总之，miR-24通过下调CARMA 3抑制膀胱癌细胞的增殖、侵袭和EMT，而CARMA 3的下调是miR-24抑制膀胱癌细胞增殖、侵袭和EMT的关键。
Increasing evidence has confirmed that dysregulation of microRNAs (miRNAs) can contribute to the progression and metastasis of human tumors. Previous studied have shown dysregulation of miR-24 in a variety of tumors. However, the roles of miR-24 in human bladder cancer have not been well clarified. Therefore, we investigated the biological functions and molecular mechanisms of miR-24 in human bladder cancer cell lines, evaluating whether it could be a therapeutic biomarker of bladder cancer in the future. In our study, we found that miR-24 is downregulated in human bladder cancer cell lines. Moreover, the low level of miR-24 was associated with increased expression of CARMA3 in bladder cancer cells. Upregulation of miR-24 significantly inhibited proliferation, arrested cell cycle and induced apoptosis in bladder cancer cells. In addition, invasion and epithelial to mesenchymal transition (EMT) of bladder cancer cells was suppressed by overexpressing miR-24. Bioinformatics analysis predicted that the CARMA3 was a potential target gene of miR-24. Further study by luciferase reporter assay demonstrated that miR-24 could directly target CARMA3. Overexpression of CARMA3 in bladder cancer cells transfected with miR-24 mimic partially reversed the inhibitory effect of miR-24. In conclusion, miR-24 inhibited cell proliferation, invasion and EMT in bladder cancer cells by downregulation of CARMA3, and that downregulation of CARMA3 was essential for the miR-24-inhibited cell proliferation, invasion and EMT in bladder cancer cells.