MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro.
Breast Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Female
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Lapatinib
/ pharmacology
MicroRNAs
/ genetics
Prognosis
Survival Analysis
Trastuzumab
/ pharmacology
Up-Regulation
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 05 2021
25 05 2021
Historique:
received:
22
01
2021
accepted:
30
04
2021
entrez:
26
5
2021
pubmed:
27
5
2021
medline:
4
11
2021
Statut:
epublish
Résumé
HER2-positive (HER2 +) breast cancer patients that do not respond to targeted treatment have a poor prognosis. The effects of targeted treatment on endogenous microRNA (miRNA) expression levels are unclear. We report that responsive HER2 + breast cancer cell lines had a higher number of miRNAs with altered expression after treatment with trastuzumab and lapatinib compared to poorly responsive cell lines. To evaluate whether miRNAs can sensitize HER2 + cells to treatment, we performed a high-throughput screen of 1626 miRNA mimics and inhibitors in combination with trastuzumab and lapatinib in HER2 + breast cancer cells. We identified eight miRNA mimics sensitizing cells to targeted treatment, miR-101-5p, mir-518a-5p, miR-19b-2-5p, miR-1237-3p, miR-29a-3p, miR-29c-3p, miR-106a-5p, and miR-744-3p. A higher expression of miR-101-5p predicted better prognosis in patients with HER2 + breast cancer (OS: p = 0.039; BCSS: p = 0.012), supporting the tumor-suppressing role of this miRNA. In conclusion, we have identified miRNAs that sensitize HER2 + breast cancer cells to targeted therapy. This indicates the potential of combining targeted drugs with miRNAs to improve current treatments for HER2 + breast cancers.
Identifiants
pubmed: 34035375
doi: 10.1038/s41598-021-90385-2
pii: 10.1038/s41598-021-90385-2
pmc: PMC8149698
doi:
Substances chimiques
MIRN101 microRNA, human
0
MicroRNAs
0
Lapatinib
0VUA21238F
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10893Références
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