Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2016.57.457
MicroRNA-124 enhances response to radiotherapy in human epidermal growth factor receptor 2-positive breast cancer cells by targeting signal transducer and activator of transcription 3
Ying Fu
; Department of General Surgery the First Affiliated Hospital ofNanchang University, Nanchang, China
Jianping Xiong
; Department of Oncology, the First Affiliated Hospital of NanchangUniversity, Nanchang, China
Sažetak
Aim To determine whether microRNA (miR)-124 enhances
the response to radiotherapy in human epidermal growth
factor receptor 2 (HER2)-positive breast cancer cells by targeting
signal transducer and activator of transcription 3
(Stat3).
Methods miR-29b expression was measured in 80 pairs of
breast tumor samples and adjacent normal tissues collected
between January 2013 and July 2014. Activity changes
of 50 canonical signaling pathways upon miR-124 overexpression
were determined using Cignal Signal Transduction
Reporter Array. Target gene of miR-124 was determined
using Targetscan and validated by Western blotting
and dual-luciferase assay. Cell death rate was assessed by
propidium iodide (PI)/Annexin V staining followed by flow
cytometry analysis. Stat3 and miR-124 expression was further
measured in 10 relapsed (non-responder) and 10 recurrence-
free HER2-positive breast cancer patients.
Results MiR-124 expression was down-regulated in HER2
positive breast cancers compared with normal tissues, and
was negatively associated with tumor size. MiR-124 overexpression
in HER2 positive breast cancer cell line SKBR3
significantly reduced the activity of Stat3 signaling pathway
compared with control transfection (P < 0.001). Bioinformatic
prediction and function assay suggested that
miR-124 directly targeted Stat3, which is a key regulator of
HER2 expression. MiR-124 overexpression down-regulated
Stat3 and potently enhanced cell death upon irradiation.
Consistently, chemical inhibitor of Stat3 also sensitized
HER2-positive breast cancer cells to irradiation. Moreover,
increased Stat3 expression and reduced miR-124 expression
were associated with a poor response to radiotherapy
in HER2-positive breast cancers.
Conclusions Weak miR-124 expression might enhance
Stat3 expression and radiotherapy resistance in HER2-positive
breast cancer cells.
Ključne riječi
Hrčak ID:
170462
URI
Datum izdavanja:
15.10.2016.
Posjeta: 883 *