WW domain binding protein 5 induces multidrug resistance of small cell lung cancer under the regulation of miR-335 through the Hippo pathway.

ABSTRACT:

Background

Our previous study indicated that WW domain binding protein 5 (WBP5) expression was elevated significantly in a drug-resistant cell compared with its parental cell. Nevertheless, its functional role and underlying mechanisms remain unknown.

Methods

In this study, WBP5 was examined in 62 small cell lung cancer (SCLC) patient samples by immunohistochemical technique. Stable WBP5-overexpressed and WBP5-underexpressed cells were further established to assess the role of WBP5 in drug resistance, apoptosis and tumour growth. We also conducted western blot to detect the expression of MST2 and YAP1 and their phosphorylated protein.

Results

The results revealed that WBP5 expression was significantly associated with the shorter survival time in SCLC patients. Upregulation of WBP5 induced multidrug resistance (MDR) and decreased apoptosis, whereas downregulation of WBP5 enhanced drug sensitivity and increased apoptosis. We also found that miR-335 negatively regulated the MDR of WBP5 by targeting its 3'UTR. Furthermore, WBP5 can lower YAP1 phosphorylation at Serine 127 and induce nuclear accumulation of YAP1. Inhibition of YAP1 by Verteporfin could blunt the MDR phenotype of WBP5.

Conclusions

WW domain binding protein 5 can modulate MDR through the Hippo pathway under the regulation of miR-335. WW domain binding protein 5 may be a prognostic predictor and a potential target for interfering with MDR in SCLC.

SUBMITTER: Tang R 

PROVIDER: S-EPMC4947702 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature