Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer

Riccardo Panella; Cody A. Cotton; Valerie A. Maymi; Sachem Best; Kelsey E. Berry; Samuel Lee; Felipe Batalini; Ioannis S. Vlachos; John G. Clohessy; Sakari Kauppinen; Pier Paolo Pandolfi

doi:10.3390/biomedicines11051470

Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer

Riccardo Panella^*, Cody A. Cotton, Valerie A. Maymi, Sachem Best, Kelsey E. Berry, Samuel Lee, Felipe Batalini, Ioannis S. Vlachos, John G. Clohessy, Sakari Kauppinen, Pier Paolo Pandolfi

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Abstract

microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and 3D cell models and a mouse xenograft model of human TNBC, respectively. Furthermore, we report that miR-22 inhibition using an LNA-modified antimiR-22 compound is effective in reducing EMT both in vitro and in vivo. Importantly, pharmacologic inhibition of miR-22 suppressed metastatic spread and markedly prolonged survival in mouse xenograft models of metastatic TNBC highlighting the potential of miR-22 silencing as a new therapeutic strategy for the treatment of TNBC.

Originalsprog	Engelsk
Artikelnummer	1470
Tidsskrift	Biomedicines
Vol/bind	11
Udgave nummer	5
ISSN	2227-9059
DOI	https://doi.org/10.3390/biomedicines11051470
Status	Udgivet - 18 maj 2023

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10.3390/biomedicines11051470Licens: CC BY 4.0

Panella et al. (2023). Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast CancerForlagets udgivne version, 3,11 MBLicens: CC BY 4.0

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title = "Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer",

abstract = "microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and 3D cell models and a mouse xenograft model of human TNBC, respectively. Furthermore, we report that miR-22 inhibition using an LNA-modified antimiR-22 compound is effective in reducing EMT both in vitro and in vivo. Importantly, pharmacologic inhibition of miR-22 suppressed metastatic spread and markedly prolonged survival in mouse xenograft models of metastatic TNBC highlighting the potential of miR-22 silencing as a new therapeutic strategy for the treatment of TNBC.",

keywords = "RNA medicine, breast cancer, microRNA",

author = "Riccardo Panella and Cotton, {Cody A.} and Maymi, {Valerie A.} and Sachem Best and Berry, {Kelsey E.} and Samuel Lee and Felipe Batalini and Vlachos, {Ioannis S.} and Clohessy, {John G.} and Sakari Kauppinen and {Paolo Pandolfi}, Pier",

year = "2023",

month = may,

day = "18",

doi = "10.3390/biomedicines11051470",

language = "English",

volume = "11",

journal = "Biomedicines",

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TY - JOUR

T1 - Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer

AU - Panella, Riccardo

AU - Cotton, Cody A.

AU - Maymi, Valerie A.

AU - Best, Sachem

AU - Berry, Kelsey E.

AU - Lee, Samuel

AU - Batalini, Felipe

AU - Vlachos, Ioannis S.

AU - Clohessy, John G.

AU - Kauppinen, Sakari

AU - Paolo Pandolfi, Pier

PY - 2023/5/18

Y1 - 2023/5/18

N2 - microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and 3D cell models and a mouse xenograft model of human TNBC, respectively. Furthermore, we report that miR-22 inhibition using an LNA-modified antimiR-22 compound is effective in reducing EMT both in vitro and in vivo. Importantly, pharmacologic inhibition of miR-22 suppressed metastatic spread and markedly prolonged survival in mouse xenograft models of metastatic TNBC highlighting the potential of miR-22 silencing as a new therapeutic strategy for the treatment of TNBC.

AB - microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and 3D cell models and a mouse xenograft model of human TNBC, respectively. Furthermore, we report that miR-22 inhibition using an LNA-modified antimiR-22 compound is effective in reducing EMT both in vitro and in vivo. Importantly, pharmacologic inhibition of miR-22 suppressed metastatic spread and markedly prolonged survival in mouse xenograft models of metastatic TNBC highlighting the potential of miR-22 silencing as a new therapeutic strategy for the treatment of TNBC.

KW - RNA medicine

KW - breast cancer

KW - microRNA

U2 - 10.3390/biomedicines11051470

DO - 10.3390/biomedicines11051470

M3 - Journal article

C2 - 37239141

SN - 2227-9059

VL - 11

JO - Biomedicines

JF - Biomedicines

IS - 5

M1 - 1470

ER -

Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer

Abstract

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