Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation

Abstract MicroRNAs (miRNAs) regulate cancer cell proliferation by binding directly to the untranslated regions of messenger RNA (mRNA). MicroRNA-148a (miR-148a) is expressed at low levels in breast cancer (BC). However, little attention has been paid to the sequestration of miR-148a. Here, we perfor...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sho Okumura, Yu Hirano, Yasuo Komatsu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19107099610c4480810bbddc1e67884e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:19107099610c4480810bbddc1e67884e
record_format	dspace
spelling	oai:doaj.org-article:19107099610c4480810bbddc1e67884e2021-12-02T15:56:56ZStable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation10.1038/s41598-021-90972-32045-2322https://doaj.org/article/19107099610c4480810bbddc1e67884e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90972-3https://doaj.org/toc/2045-2322Abstract MicroRNAs (miRNAs) regulate cancer cell proliferation by binding directly to the untranslated regions of messenger RNA (mRNA). MicroRNA-148a (miR-148a) is expressed at low levels in breast cancer (BC). However, little attention has been paid to the sequestration of miR-148a. Here, we performed a knockdown of miR-148a using anti-miRNA oligonucleotides (AMOs) and investigated the effect on BC cell proliferation. BC cell proliferation was significantly suppressed by AMO flanked by interstrand cross-linked duplexes (CL-AMO), whereas single-stranded and commercially available AMOs had no effect. The suppression was caused by sequestering specifically miR-148a. Indeed, miR-148b, another member of the miR-148 family, was not affected. Importantly, the downregulation of miR-148a induced a greater and longer-lasting inhibition of BC cell proliferation than the targeting of oncogenic microRNA-21 (miR-21) did. We identified thioredoxin-interacting protein (TXNIP), a tumor suppressor gene, as a target of miR-148a and showed that CL-AMO provoked an increase in TXNIP mRNA expression. This study provide evidence that lowly expressed miRNAs such as miR-148a have an oncogenic function and might be a promising target for cancer treatment.Sho OkumuraYu HiranoYasuo KomatsuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sho Okumura Yu Hirano Yasuo Komatsu Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation
description	Abstract MicroRNAs (miRNAs) regulate cancer cell proliferation by binding directly to the untranslated regions of messenger RNA (mRNA). MicroRNA-148a (miR-148a) is expressed at low levels in breast cancer (BC). However, little attention has been paid to the sequestration of miR-148a. Here, we performed a knockdown of miR-148a using anti-miRNA oligonucleotides (AMOs) and investigated the effect on BC cell proliferation. BC cell proliferation was significantly suppressed by AMO flanked by interstrand cross-linked duplexes (CL-AMO), whereas single-stranded and commercially available AMOs had no effect. The suppression was caused by sequestering specifically miR-148a. Indeed, miR-148b, another member of the miR-148 family, was not affected. Importantly, the downregulation of miR-148a induced a greater and longer-lasting inhibition of BC cell proliferation than the targeting of oncogenic microRNA-21 (miR-21) did. We identified thioredoxin-interacting protein (TXNIP), a tumor suppressor gene, as a target of miR-148a and showed that CL-AMO provoked an increase in TXNIP mRNA expression. This study provide evidence that lowly expressed miRNAs such as miR-148a have an oncogenic function and might be a promising target for cancer treatment.
format	article
author	Sho Okumura Yu Hirano Yasuo Komatsu
author_facet	Sho Okumura Yu Hirano Yasuo Komatsu
author_sort	Sho Okumura
title	Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation
title_short	Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation
title_full	Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation
title_fullStr	Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation
title_full_unstemmed	Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation
title_sort	stable duplex-linked antisense targeting mir-148a inhibits breast cancer cell proliferation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/19107099610c4480810bbddc1e67884e
work_keys_str_mv	AT shookumura stableduplexlinkedantisensetargetingmir148ainhibitsbreastcancercellproliferation AT yuhirano stableduplexlinkedantisensetargetingmir148ainhibitsbreastcancercellproliferation AT yasuokomatsu stableduplexlinkedantisensetargetingmir148ainhibitsbreastcancercellproliferation
_version_	1718385375373688832

Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation

Ejemplares similares