High expression of RAB38 promotes malignant progression of pancreatic cancer

RAB38高表达促进胰腺癌恶性进展

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作者:Bao-Yu Li ,Li-Jie He ,Xiang-Lian Zhang ,Hui Liu ,Bin Liu

Abstract

Ras‑Related Protein Rab‑38 (RAB38), which belongs to the RAB family, is involved in the biogenesis of lysosome‑related organelles and defense against certain microbial infections. However, the clinical significance and potential function of RAB38 in pancreatic adenocarcinoma remain unclear. In the present study, an immunohistochemical assay was performed to analyze the expression of RAB38 in pancreatic adenocarcinoma tumor specimens from 82 patients, and the clinicopathological characteristics and survival rate of these patients were further examined. To validate the role of RAB38 in tumors, the effect of RAB38 on tumor cell proliferation, migration and invasion was assessed by establishing RAB38 knockdown cell lines. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to examine the expression levels of proteins associated with the cancer cell behavior. In addition, the inhibitory effect of RAB38 silencing on pancreatic cancer was examined in mice. The immunohistochemistry results revealed that RAB38 was upregulated and positively correlated with the grade of progression in pancreatic adenocarcinoma patients. Further investigation indicated that RAB38 downregulation significantly suppressed the proliferation, migration and invasive capacity of pancreatic cancer cells, as well as decreased the expression levels of Ki67, proliferating cell nuclear antigen, and matrix metalloproteinases 2 and 9. RAB38 silencing also inhibited the development of pancreatic cancer in vivo. Taken together, a high level of RAB38 was significantly associated with the malignant phenotypes of pancreatic cancer, suggesting that RAB38 may serve as a novel biomarker and a potential therapeutic target for pancreatic cancer. Keywords: RAB38; clinicopathological characteristics; pancreatic cancer; RNA interference; in vitro; in vivo.

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