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. 2017 Sep 1;7(9):1863-1873.
eCollection 2017.

MiRNA-107 enhances chemosensitivity to paclitaxel by targeting antiapoptotic factor Bcl-w in non small cell lung cancer

Chaojing Lu  1 , Zhibing Xie  2 , Qingzhen Peng  2
Affiliations

MiRNA-107 enhances chemosensitivity to paclitaxel by targeting antiapoptotic factor Bcl-w in non small cell lung cancer

Chaojing Lu et al. Am J Cancer Res. .

Abstract

The aim of this study is to elucidate whether and how miR-107 participates in the modulation of paclitaxel sensitivity in non small cell lung cancer (NSCLC). By qRT-PCR, we found that miR-107 is significantly down-regulated in paclitaxel-resistant A549/Taxol cells compared with corresponding paclitaxel-sensitive counterparts. Overexpression of miR-107 suppresses paclitaxel resistance of A549/Taxol cells through directly inhibiting Bcl-w. Overexpression of miR-107 promotes apoptosis and inhibits proliferation and mobility of A549/Taxol cells under treatment with paclitaxel in vitro. Moreover, miR-107 inhibits in vivo paclitaxel resistance in xenograft model. MiR-107/Bcl-w axis regulates paclitaxel chemoresistance through PI3K-Akt pathway. Our results suggest that up-regulation of miR-107 resensitizes paclitaxel-resistant NSCLC cells by targeting Bcl-w, which reveals a potential mechanism of miR-107 in reversing drug resistance.

Keywords: Bcl-w; Non small cell lung cancer; PI3K-Akt pathway; chemoresistance; microRNA-107.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
MiR-107 is down-regulated in paclitaxel-resistant NSCLC cells. Analysis of miR-107 expression levels was performed by qRT-PCR. U6 was used as the endogenous control. Data are presented as means ± SDs, and *P<0.05 was considered to be statistically significant.
Figure 2
Figure 2
Bcl-w is a target of miR-107. (A) The miR-107 binding sites in the Bcl-w 3’UTR predicted by bioinformatics analysis. (B) Luciferase activities in HEK293T cells were measured by Dual-luciferase reporter assay. qRT-PCR (C) and western blot (D) showing Bcl-w mRNA and protein expression levels in A549/Taxol cells with miR-107 overexpression. GAPDH was used as the endogenous control. Data are presented as means ± SDs, and *P<0.05 was considered to be statistically significant.
Figure 3
Figure 3
MiR-107 overexpression promotes paclitaxel sensitivity of A549/Taxol cells. The cell viability (A) was determined by MTT assay at 0, 2, 4, 8, 16, 32, 64 nM paclitaxel, and IC50 values (B) were subsequently calculated. Data are presented as means ± SDs, and *P<0.05 was considered to be statistically significant.
Figure 4
Figure 4
MiR-107 overexpression promotes apoptosis and inhibits mobility of A549/Taxol cells in treatment with paclitaxel in vitro. A. The percentages of apoptotic cells analyzed by flow cytometry. B. Cell apoptosis was determined by caspase-3 activity assay. C. Wound-healing assay was performed to determine cell mobility. Data are presented as means ± SDs, and *P<0.05 was considered to be statistically significant.
Figure 5
Figure 5
MiR-107 overexpression inhibits paclitaxel resistance in vivo. A. Tumor volume was measured and calculated every three days. B. Tumor weight was measured after four weeks of implantation. C. Representative pictures of xenograft tumors in four groups. Data are presented as means ± SDs, and *P<0.05 was considered to be statistically significant.
Figure 6
Figure 6
MiR-107/Bcl-w axis regulates paclitaxel chemoresistance through PI3K-Akt pathway. Levels of p-Akt and p-GSK3β in cell lysates were analyzed by western blotting using GAPDH as a loading control. Data are presented as means ± SDs, and *P<0.05 was considered to be statistically significant.
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