Journal
ONCOLOGY REPORTS
Volume 33, Issue 3, Pages 1215-1220Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.3713
Keywords
miRNA-542-3p; trastuzumab; drug resistance; AKT
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Funding
- National Science and Technology Support Program [2013BAI09B08]
- Tianjin Municipal Major Scientific and Technological Special Project for Significant Anticancer Development [12ZCDZSY15700]
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Trastuzumab (Herceptin) has been widely used in breast cancer treatment. However, the majority of cancers that initially respond to trastuzumab begin to progress again within 1 year. Despite the high resistance rate, the molecular mechanisms underlying this desease are not well understood. In the present study, microRNA (miRNA-542-3p modulated trastuzumab resistance in SKBR3 and MCF7/Her2 breast cancer cell lines. Trastuzumab induced miRNA-542-3p expression in SKBR3 and MCF7/Her2 cells. Furthermore, knockdown of miRNA-542-3p in the two cell lines resulted in decreased drug sensitivity to trastuzumab and cell apoptosis. The blockage of G1/S checkpoint by trastuzumab was rescued as well. miRNA-542-3p knockdown also activated the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, while LY294002 reversed the effect of miRNA-542-3p knockdown. In summary, the results suggested that miRNA-542-3p downregulation may contribute to the trastuzumab resistance in breast cancer via, at least in part, the PI3K-akt pathway. Our findings provide new molecular mechanisms in trastuzumab resistance.
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