MiR-363-3p induces tamoxifen resistance in breast cancer cells through PTEN modulation

Abstract Nowadays, the investigation for overcoming tamoxifen (TAM) resistance is confronting a considerable challenge. Therefore, immediate attention is required to elucidate the mechanism underlying TAM resistance in breast cancer. This research primarily aimed to define how miRNA-363-3p facilitat...

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Main Authors: Yaning Liang, Cuiyu Shi, Yu Wang, Bingjie Fan, Wei Song, Rong Shen
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-83938-8
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author Yaning Liang
Cuiyu Shi
Yu Wang
Bingjie Fan
Wei Song
Rong Shen
author_facet Yaning Liang
Cuiyu Shi
Yu Wang
Bingjie Fan
Wei Song
Rong Shen
author_sort Yaning Liang
collection DOAJ
description Abstract Nowadays, the investigation for overcoming tamoxifen (TAM) resistance is confronting a considerable challenge. Therefore, immediate attention is required to elucidate the mechanism underlying TAM resistance in breast cancer. This research primarily aimed to define how miRNA-363-3p facilitates resistance to TAM in breast cancer. High-throughput miRNA sequencing was performed using RNAs prepared from breast cancer MCF-7 cells and TAM-resistant MCF-7 cells (MCF-7-TAM). An increase in miRNA-363-3p levels was observed in MCF-7-TAM cells. In MCF-7 cells, miRNA-363-3p directly targeted and negatively regulated phosphatase and tensin homolog (PTEN). Reduction of miRNA-363-3p retarded cell growth and accelerated cell apoptosis, thereby enhancing the sensitivity of TAM. Moreover, analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed significant enrichment of target genes within the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Ultimately, miR-363-3p decreased the responsiveness of breast cancer cells to TAM by targeting and suppressing PTEN through a mechanism associated with the PI3K-Akt pathway. Therefore, these results suggest that miR-363-3p-dependent PTEN expression contributes to the mechanisms underlying breast cancer endocrine resistance.
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spelling doaj-art-7f027abbd19043e8a03242e5ec3bc9e82025-08-20T02:53:58ZengNature PortfolioScientific Reports2045-23222024-12-0114111410.1038/s41598-024-83938-8MiR-363-3p induces tamoxifen resistance in breast cancer cells through PTEN modulationYaning Liang0Cuiyu Shi1Yu Wang2Bingjie Fan3Wei Song4Rong Shen5Department of Minimally Invasive Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Minimally Invasive Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityTumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityCancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Minimally Invasive Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Minimally Invasive Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityAbstract Nowadays, the investigation for overcoming tamoxifen (TAM) resistance is confronting a considerable challenge. Therefore, immediate attention is required to elucidate the mechanism underlying TAM resistance in breast cancer. This research primarily aimed to define how miRNA-363-3p facilitates resistance to TAM in breast cancer. High-throughput miRNA sequencing was performed using RNAs prepared from breast cancer MCF-7 cells and TAM-resistant MCF-7 cells (MCF-7-TAM). An increase in miRNA-363-3p levels was observed in MCF-7-TAM cells. In MCF-7 cells, miRNA-363-3p directly targeted and negatively regulated phosphatase and tensin homolog (PTEN). Reduction of miRNA-363-3p retarded cell growth and accelerated cell apoptosis, thereby enhancing the sensitivity of TAM. Moreover, analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed significant enrichment of target genes within the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Ultimately, miR-363-3p decreased the responsiveness of breast cancer cells to TAM by targeting and suppressing PTEN through a mechanism associated with the PI3K-Akt pathway. Therefore, these results suggest that miR-363-3p-dependent PTEN expression contributes to the mechanisms underlying breast cancer endocrine resistance.https://doi.org/10.1038/s41598-024-83938-8Hsa-miR-363-3pBreast cancerPTENTAM resistancePI3K/AKT signaling pathway
spellingShingle Yaning Liang
Cuiyu Shi
Yu Wang
Bingjie Fan
Wei Song
Rong Shen
MiR-363-3p induces tamoxifen resistance in breast cancer cells through PTEN modulation
Scientific Reports
Hsa-miR-363-3p
Breast cancer
PTEN
TAM resistance
PI3K/AKT signaling pathway
title MiR-363-3p induces tamoxifen resistance in breast cancer cells through PTEN modulation
title_full MiR-363-3p induces tamoxifen resistance in breast cancer cells through PTEN modulation
title_fullStr MiR-363-3p induces tamoxifen resistance in breast cancer cells through PTEN modulation
title_full_unstemmed MiR-363-3p induces tamoxifen resistance in breast cancer cells through PTEN modulation
title_short MiR-363-3p induces tamoxifen resistance in breast cancer cells through PTEN modulation
title_sort mir 363 3p induces tamoxifen resistance in breast cancer cells through pten modulation
topic Hsa-miR-363-3p
Breast cancer
PTEN
TAM resistance
PI3K/AKT signaling pathway
url https://doi.org/10.1038/s41598-024-83938-8
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AT bingjiefan mir3633pinducestamoxifenresistanceinbreastcancercellsthroughptenmodulation
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