Details

Autor(en) / Beteiligte

• Jin, Juan
• Sun, Zijia
• Yang, Fang
• Tang, Lin
• Chen, Weiwei
• Guan, Xiaoxiang

Titel

miR-19b-3p inhibits breast cancer cell proliferation and reverses saracatinib-resistance by regulating PI3K/Akt pathway

Ist Teil von

• Archives of biochemistry and biophysics, 2018-05, Vol.645, p.54-60

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Breast cancer arises as the most frequent malignancy, and causes the majority of cancer death among females worldwide. Src is a tyrosine kinase identified as the product of the proto-oncogene and is supposed to promote cancer development and metastasis. Src inhibitors are recently developed and have shown efficacy in breast cancer. Increasing evidences suggest that aberrant expression of miRNAs is involved in cancer development and drug resistance. Identifying miRNAs associated with drug resistance may enhance the sensitivity of targeted therapies, including Src inhibitors. In this study, we established a Src inhibitor saracatinib-resistant breast cancer cell line (SK-BR-3/SI) for the first time. Microarray data and qRT-PCR results showed that miR-19b-3p expression was downregulated in saracatinib-resistant cells compared with saracatinib-sensitive cells. Downregulation of miR-19b-3p remarkably increased the IC50 value of saracatinib, and promoted cell migration. Further studies found that miR-19b-3p reduced PIK3CA expression by directly targeting PIK3CA gene and the resistance of Src inhibitor might be associated with activation of PI3K/Akt pathway after downregulation of miR-19b-3p. Moreover, we demonstrated that PI3K inhibitor LY294002 could reverse saracatinib resistance in saracatinib-resistant cells, which deserved further preclinical and clinical evaluation of dual inhibition of Src and PI3K in breast cancer. •Src inhibitor saracatinib-resistant breast cancer cell line (SK-BR-3/SI) was first established.•Microarray data found that miR-19b-3p expression was downregulated in SK-BR-3/SI compared to SK-BR-3.•Downregulation of miR-19b-3p might induce resistance of Src inhibitor by activating PI3K/Akt pathway.•PI3K inhibitor LY294002 could reverse saracatinib resistance in saracatinib-resistant cells.