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

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 tr...

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Detalles Bibliográficos
Autores principales: Li, Sha, Xu, Jian‐Jun, Zhang, Qing‐Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778625/
https://www.ncbi.nlm.nih.gov/pubmed/31389121
http://dx.doi.org/10.1111/cas.14164
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author Li, Sha
Xu, Jian‐Jun
Zhang, Qing‐Yun
author_facet Li, Sha
Xu, Jian‐Jun
Zhang, Qing‐Yun
author_sort Li, Sha
collection PubMed
description 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.
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spelling pubmed-67786252019-10-11 MicroRNA‐132‐3p inhibits tumor malignant progression by regulating lysosomal‐associated protein transmembrane 4 beta in breast cancer Li, Sha Xu, Jian‐Jun Zhang, Qing‐Yun Cancer Sci Original Articles 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. John Wiley and Sons Inc. 2019-08-19 2019-10 /pmc/articles/PMC6778625/ /pubmed/31389121 http://dx.doi.org/10.1111/cas.14164 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Li, Sha
Xu, Jian‐Jun
Zhang, Qing‐Yun
MicroRNA‐132‐3p inhibits tumor malignant progression by regulating lysosomal‐associated protein transmembrane 4 beta in breast cancer
title MicroRNA‐132‐3p inhibits tumor malignant progression by regulating lysosomal‐associated protein transmembrane 4 beta in breast cancer
title_full MicroRNA‐132‐3p inhibits tumor malignant progression by regulating lysosomal‐associated protein transmembrane 4 beta in breast cancer
title_fullStr MicroRNA‐132‐3p inhibits tumor malignant progression by regulating lysosomal‐associated protein transmembrane 4 beta in breast cancer
title_full_unstemmed MicroRNA‐132‐3p inhibits tumor malignant progression by regulating lysosomal‐associated protein transmembrane 4 beta in breast cancer
title_short MicroRNA‐132‐3p inhibits tumor malignant progression by regulating lysosomal‐associated protein transmembrane 4 beta in breast cancer
title_sort microrna‐132‐3p inhibits tumor malignant progression by regulating lysosomal‐associated protein transmembrane 4 beta in breast cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778625/
https://www.ncbi.nlm.nih.gov/pubmed/31389121
http://dx.doi.org/10.1111/cas.14164
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