Correlation between long non-coding RNAs (lncRNAs) H19 expression and trastuzumab resistance in breast cancer
J Cancer Res Ther
;
2019 Aug; 15(4): 933-940
Article
| IMSEAR
| ID: sea-213457
ABSTRACT
Introduction:
Trastuzumab resistance is a major obstacle encountered in human epidermal growth factor receptor 2 (HER2)-positive breast cancer therapy. Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in both tumorigenesis and tumor development. However, whether lncRNAs are associated with trastuzumab resistance is not yet clear. Subjects andMethods:
We evaluated trastuzumab sensitivity in breast cancer cell lines, SKBR3, HCC1954, and MDA-MB-231. We also evaluated H19 expression in these cell lines after treatment with different trastuzumab concentrations. Besides, H19 was downregulated to investigate its role in cell viability and trastuzumab sensitivity and a trastuzumab resistance cell line was cultured to verify the effect of H19 in trastuzumab resistance. Forty-eight HER2-positive breast cancer patients treated with trastuzumab in the first-line setting were selected retrospectively to explore the relationship between H19 expression and tumor-node-metastasis (TNM) stage as well as trastuzumab resistance.Results:
H19 is a trastuzumab-responsive lncRNA and its expression was upregulated in a trastuzumab-resistant breast cancer cell. Downregulation of H19 restored the sensitivity of trastuzumab-resistant cells to this drug. The expression of H19 significantly correlated with TNM stage. Patients with higher expression of H19 showed an evidently shorter progression-free survival than those with low H19 expression. H19 overexpression was negatively correlated to the trastuzumab-therapy response.Conclusions:
Our results provide evidence for the H19-mediated regulation of trastuzumab resistance in HER2-positive breast cancer cells. H19 could act as a potential predictive biomarker for HER2-positive breast cancer patients, and downregulation of H19 could reverse trastuzumab resistance and enhance the inhibitory function of this drug
Full text:
Available
Index:
IMSEAR (South-East Asia)
Type of study:
Prognostic study
Journal:
J Cancer Res Ther
Journal subject:
Neoplasms
/
Therapeutics
Year:
2019
Type:
Article
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