MicroRNA-132-3p inhibits tumor malignant progression by regulating lysosomal-associated protein transmembrane 4 beta in breast cancer
MicroRNA-132-3p inhibits tumor malignant progression by regulating lysosomal-associated protein transmembrane 4 beta in breast cancer
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MicroRNA-132-3p通过调节乳腺癌中溶酶体相关蛋白跨膜4β抑制肿瘤恶性进展
DOI：
10.1111/cas.14164
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发表时间：
2019-08-19
期刊：
影响因子：
5.7
通讯作者：
Zhang, Qing-Yun
中科院分区：
文献类型：
--
作者：
Li, Sha;Xu, Jian-Jun;Zhang, Qing-Yun
溶酶体相关蛋白跨膜4 β（LAPTM 4 B）是一种原癌基因，已被证明是癌症进展中的正调控因子。然而，LAPTM 4 B调控的机制尚未完全阐明。异常microRNAs（miRNAs）可以通过干扰靶转录物和/或翻译来调节基因表达，从而在乳腺癌中发挥肿瘤抑制或致癌作用。本研究通过荧光素酶报告基因和蛋白质印迹实验证实了miR-132- 3 p与LAPTM 4 B的3 '非翻译区（3 ' UTR）直接结合，负调控LAPTM 4 B的表达。随后，我们验证了miR-132- 3 p在乳腺癌组织中下调。受试者工作特征曲线分析表明miR-132- 3 p具有准确的诊断价值，Kaplan-Meier和考克斯回归模型显示miR-132- 3 p是潜在的复发预后标志物，在乳腺癌患者中显示低水平。此外，我们发现miR-132- 3 p与上述样品中的LAPTM 4 B表达呈负相关。在功能上，miR-132- 3 p通过介导上皮-间质转化信号抑制乳腺癌细胞通过LAPTM 4 B的迁移和侵袭，并通过抑制PI 3 K-AKT-mTOR信号通路部分逆转LAPTM 4 B的致癌作用。综上所述，这些发现首次全面分析了miR-132- 3 p作为直接靶向LAPTM 4 B的miRNA，并阐明了miR-132- 3 p/LAPTM 4 B作为参与乳腺癌发生和转移的重要功能轴。
Lysosomal-associated protein transmembrane 4 beta (LAPTM4B), a proto-oncogene, has been shown to be a positive modulator in cancer progression. However, the mechanism of LAPTM4B regulation is not fully elucidated. Aberrant microRNAs (miRNAs) can regulate gene expression by interfering with target transcripts and/or translation to exert tumor-suppressive or oncogenic effects in breast cancer. In the present study, miR-132-3p, which was predicted by relevant software, was confirmed to directly bind to the 3 ' untranslated region (3 ' UTR) of LAPTM4B and negatively regulate its expression in luciferase reporter and western blot assays. Subsequently, we validated that miR-132-3p was downregulated in breast cancer tissues. Receiver-operating characteristic curve analysis indicated that miR-132-3p had accurate diagnostic value, and a Kaplan-Meier and Cox regression model showed that miR-132-3p was a potential prognostic marker for recurrence, showing low levels in breast cancer patients. In addition, we showed that miR-132-3p was inversely correlated with LAPTM4B expression in the above samples. Functionally, miR-132-3p suppressed the migration and invasion of breast carcinoma cells through LAPTM4B by mediating epithelial-mesenchymal transition signals, and partially reversed the carcinogenic effects of LAPTM4B by inhibiting the PI3K-AKT-mTOR signaling pathway. Taken together, these findings provide the first comprehensive analysis of miR-132-3p as a direct LAPTM4B-targeted miRNA, and shed light on miR-132-3p/LAPTM4B as a significant functional axis involved in the oncogenesis and metastasis of breast cancer.