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MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer.


ABSTRACT:

Background

Gallbladder cancer (GBC) is a malignant tumor highly resistant to chemotherapy. MicroRNAs (miRNAs) are found extensively involved in modulation of carcinogenesis and chemoresistance. This study aimed to investigate cisplatin (DDP)-susceptibility regulated by expression of the miRNAs and underlying pathways in GBC.

Results

The microRNA-31 (miR-31) was selected by microarray due to the biggest fold change between DDP-resistant and parental cells. Ectopic overexpression of miR-31 decreased cell proliferation, viability and invasion capacity, but promoted apoptosis in DDP-resistant cells and in xenograft tumor models. Cell apoptosis and DDP-chemosensitivity was remarkably increased by knockdown of Src proto-oncogene (Src) expression, which was subsequently reversed by rescue of Src expression in miR-31-expressing cells.

Methods

The microarray was used to select the candidate miRNA in two DDP-resistant GBC cell lines. The effect of regulated expression of the miRNA on cell migration, invasion, proliferation and apoptosis was examined by wound healing, transwell assays, CCK-8 assays, colony formation and flow cytometry assays, respectively. Xenograft tumor models were used to validate the function of the downstream target.

Conclusion

Our results demonstrated that miR-31reduced significantly in GBC cells rendering resistance to cisplatin, and upregulated expression of miR-31 augmented chemosensitivity, presenting a therapeutic potential to overcome drug resistance in GBC.

SUBMITTER: Li M 

PROVIDER: S-EPMC5347753 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer.

Li Maolan M   Chen Wei W   Zhang Hongchen H   Zhang Yong Y   Ke Fayong F   Wu Xiangsong X   Zhang Yijian Y   Weng Mingzhe M   Liu Yingbin Y   Gong Wei W  

Oncotarget 20161201 50


<h4>Background</h4>Gallbladder cancer (GBC) is a malignant tumor highly resistant to chemotherapy. MicroRNAs (miRNAs) are found extensively involved in modulation of carcinogenesis and chemoresistance. This study aimed to investigate cisplatin (DDP)-susceptibility regulated by expression of the miRNAs and underlying pathways in GBC.<h4>Results</h4>The microRNA-31 (miR-31) was selected by microarray due to the biggest fold change between DDP-resistant and parental cells. Ectopic overexpression of  ...[more]

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