Publication: Hsa-miR-221-3p promotes proliferation and migration in HER2-positive breast cancer cells by targeting LASS2 and MBD2
Authors
Shao, Xiying ; Zheng, Yabing ; Huang, Yuan ; Li, Guangliang ; Zou, Weibin ; Shi, Lei
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-483
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info:eu-repo/semantics/article
Description
Abstract
. Background. Human epidermal growth factor
receptor (HER2)-positive breast cancers account for
nearly 20% of all breast cancer cases and microRNAs
(miRNAs) play crucial roles in disease progression. The
study was aimed to explore the role of miR-221-3p in
HER2-positive breast cancer.
Methods. Differentially expressed miRNAs were
identified by high-throughput sequencing. Quantitative
real-time PCR was used to evaluate mRNA levels of
corresponding genes. CKK8 and transwell assays were
performed to evaluate cell viability and migration. The
translation binding was assessed by luciferase assay.
Results. Hsa-miR-221-3p was highly upregulated in
HER2-positive breast cancer samples, particularly in
patients with advanced or metastatic disease, as
compared to healthy controls. miR-221-3p upregulation
using mimics promoted cell proliferation and migration
in HER2-positive cell lines, whereas miR-221-3p
suppression had the opposite effect. Additionally, miR221-3p mimics reduced the expression levels of LASS2
and MBD2 in HER2-positive breast cancer cells;
conversely, miR-221-3p inhibition upregulated LASS2
and MBD2. miR-221-3p inhibited the translation of
LASS2 and MBD2 by directly binding to their 3′-
untranslated regions. Forced expression of LASS2 and
MBD2 significantly attenuated the ability of miR-221-3p
mimics to enhance cell growth and migration in HER2-
positive but not in HER2-negative breast cancer cells. In
HER-2-positive breast cancer patients, the levels of miR221-3p were negatively correlated with the mRNA levels
of LASS2 and MBD2.
Conclusions. Upregulation of hsa-miR-221-3 in
HER2-positive breast cancer contributes to cancer cell
proliferation and migration by directly targeting the
tumor suppressors LASS2 and MBD2. Therefore, the
hsa-miR-221-3 may serve as a promising and actionable
therapeutic target in HER2-positive breast cancer.
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Citation
Histology and Histopathology Vol. 37, nº11 (2022)
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