MicroRNA-136-5p regulates gemcitabine resistance in pancreatic cancer via down-regulating ZNF32

Y. Xu, Y. Qin, J.-X. Cui, J. Xu

Department of Gastroenterology, Linyi Central Hospital, Linyi, China. 2973962097@qq.com

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• Oncology

OBJECTIVE: We explored the regulation of microRNA-136-5p on gemcitabine resistance of pancreatic cancer (PCa) and further highlighted the crosstalk between microRNA-136-5p and ZNF32, so as to provide an effective theoretical basis for target treatment of PCa.

PATIENTS AND METHODS: MicroRNA-136-5p and ZNF32 levels in tumor specimens of 48 patients with PCa were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) method, and the interplay between microRNA-136-5p and clinicopathological parameters, as well as prognosis of those patients was also analyzed. Meanwhile, in gemcitabine-resistant PCa cell lines PANC-1 and CFPAC-1, microRNA-136-5p overexpression model was constructed, and cell counting kit-8 (CCK-8), transwell, as well as cell wound healing assays were carried out to assess the impact of microRNA-136-5p on PCa cell functions. Finally, Luciferase assay and recovery experiments were conducted to specify the precise underlying mechanism.

RESULTS: qRT-PCR results revealed a significant low expression of microRNA-136-5p both in tumor tissues of PCa patients and in PCa cell lines compared to the normal control groups. In addition, microRNA-136-5p mimics markedly attenuated the proliferation and migration abilities of the gemcitabine-resistant PCa cell lines. The Luciferase assay verified certain binding sites between microRNA-136-5p and ZNF32, while qPCR results indicated a negative correlation between the two in PCa tissues. Moreover, recovery experiments demonstrated that ZNF32 overexpression reversed the inhibitory effect on the malignant progression of gemcitabine-resistant PCa cells induced by microRNA-136-5p.

CONCLUSIONS: MicroRNA-136-5p can reduce the proliferation rate and metastasis ability of PCa cells via regulating ZNF32, and thus alleviates gemcitabine resistance in PCa cells.

 

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