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

• Published in: Cancer science 2019-10, Vol.110 (10), p.3098-3109
• Main Authors: Li, Sha, Xu, Jian‐Jun, Zhang, Qing‐Yun
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 3' Untranslated Regions; AKT protein; Binding sites; Breast cancer; Breast carcinoma; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Epithelial-Mesenchymal Transition; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Humans; LAPTM4B; MCF-7 Cells; Medical prognosis; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mesenchyme; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; miRNA; miR‐132‐3p; Neoplasm Invasiveness; Neoplasm Staging; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Original; Phosphorylation; Proteins; Regulation; ROC Curve; Signal Transduction; Studies; Survival Analysis; TOR protein; Tumorigenesis; Tumors
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14164

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. This study shows that miR‐132‐3p directly targets LAPTM4B, which may suppress the biological function of LAPTM4B through the PI3K‐AKT‐mTOR signaling pathway, highlighting the clinical potential of these factors as therapeutic targets and promising prognostic markers in breast cancer.