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29.09.2018 | Original Article | Ausgabe 1/2019

Virchows Archiv 1/2019

Rab14 overexpression regulates gemcitabine sensitivity through regulation of Bcl-2 and mitochondrial function in pancreatic cancer

Zeitschrift:
Virchows Archiv > Ausgabe 1/2019
Autoren:
Jinnian Ge, Chunlin Ge
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00428-018-2455-5) contains supplementary material, which is available to authorized users.

Abstract

Rab family protein Rab14 has been implicated in the development of human cancers. To date, its expression pattern, biological function, and potential mechanism in pancreatic cancer have not been explored. In this study, we analyzed Rab14 expression in 103 cases of pancreatic cancer tissues using immunohistochemistry (IHC) and found that Rab14 was overexpressed in 41/103 cases (39.8%). Rab14 overexpression correlated with the advanced stage. Moreover, elevated Rab14 levels indicated poor prognosis of patients with pancreatic cancers. We used BxPC-3 and Capan-2 respectively for plasmid and siRNA transfection. MTT and colony formation assays showed that Rab14 transfection increased cell proliferation and colony formation in BxPC-3 cells. Rab14 siRNA knockdown inhibits proliferation and colony formation ability in Capan-2 cell line. Cell cycle analysis showed that Rab14 facilitated cell cycle progression. Matrigel invasion assay showed that Rab14 promoted BxPC-3 cell invasion while its depletion inhibited Capan-2 cell invasion. In addition, MTT and AnnexinV/PI analysis demonstrated that overexpression of Rab14 reduced gemcitabine sensitivity which conversely was increased by Rab14 knockdown. We also demonstrated that Rab14 upregulated mitochondrial membrane potential (MMP) while its depletion downregulated MMP during gemcitabine treatment. In addition, western blotting revealed that Rab14 overexpression upregulated cyclin D1, cyclin A, cyclin E, p-Rb, and Bcl-2 and downregulated p21. Rab14 also downregulated caspase3, PARP cleavage, and cytochrome c release. In conclusion, our data indicated that Rab14 was overexpressed in pancreatic cancer and promotes growth and gemcitabine resistance, possibly through regulation of mitochondrial function and Bcl-2.

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ESM 1 (DOC 53 kb)
428_2018_2455_MOESM1_ESM.doc
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