MicroRNA-132-3p inhibits tumor malignant progression by regulating lysosomal-associated protein transmembrane 4 beta in breast cancer

被引:35
作者
Li, Sha [1 ]
Xu, Jian-Jun [1 ]
Zhang, Qing-Yun [1 ]
机构
[1] Peking Univ, Canc Hosp & Inst, Dept Clin Lab, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
breast cancer; LAPTM4B; metastasis; miR-132-3p; regulation; INDEPENDENT PROGNOSTIC MARKER; CELL-PROLIFERATION; TETRATRANSMEMBRANE PROTEIN; PROSTATE-CANCER; POOR-PROGNOSIS; LAPTM4B; OVEREXPRESSION; METASTASIS; EXPRESSION; RESISTANCE;
D O I
10.1111/cas.14164
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3098 / 3109
页数:12
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