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The role of miR-26a and miR-30b in HER2+ breast cancer trastuzumab resistance and regulation of the CCNE2 gene.
- Source :
-
Scientific reports [Sci Rep] 2017 Jan 25; Vol. 7, pp. 41309. Date of Electronic Publication: 2017 Jan 25. - Publication Year :
- 2017
-
Abstract
- A subset of HER2+ breast cancer patients manifest clinical resistance to trastuzumab. Recently, miR-26a and miR-30b have been identified as trastuzumab response regulators, and their target gene CCNE2 seems to play an important role in resistance to trastuzumab therapy. Cell viability was evaluated in trastuzumab treated HER2+ BT474 wt (sensitive), BT474r (acquired resistance), HCC1954 (innate resistance), and MDA-MB-231 (HER2-) cell lines, and the expression of miR-26a, miR-30b, and their target genes was measured. BT474 wt cell viability decreased by 60% and miR-26a and miR-30b were significantly overexpressed (~3-fold, p = 0.003 and p = 0.002, respectively) after trastuzumab treatment, but no differences were observed in resistant and control cell lines. Overexpression of miR-30b sensitized BT474r cells to trastuzumab (p = 0.01) and CCNE2, was significantly overexpressed after trastuzumab treatment in BT474r cells (p = 0.032), but no significant changes were observed in sensitive cell line. When CCNE2 was silenced BT474r cell sensitivity to trastuzumab increased (p = 0.03). Thus, the molecular mechanism of trastuzumab action in BT474 cell line may be regulated by miR-26a and miR-30b and CCNE2 overexpression might play an important role in acquired trastuzumab resistance in HER2+ breast cancer given that resistance was diminished when CCNE2 was silenced.
- Subjects :
- Cell Cycle drug effects
Cell Cycle genetics
Cell Line, Tumor
Cell Survival drug effects
Cell Survival genetics
Cyclins metabolism
Down-Regulation drug effects
Down-Regulation genetics
Drug Resistance, Neoplasm genetics
Female
Gene Silencing
Humans
MicroRNAs genetics
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
Trastuzumab pharmacology
Breast Neoplasms drug therapy
Breast Neoplasms genetics
Cyclins genetics
Gene Expression Regulation, Neoplastic drug effects
MicroRNAs metabolism
Receptor, ErbB-2 metabolism
Trastuzumab therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28120942
- Full Text :
- https://doi.org/10.1038/srep41309