Abstract
BackgroundPim-1 (Provirus integration site for Moloney murine leukemia virus 1) belongs to the Ser/Thr kinase family and plays a pivotal role in occurrence and development of oncogenesis. Recent studies have demonstrated that Pim-1 phosphorylates RUNX3 and alters its subcellular localization. However, few studies have concerned the implications of Pim-1 in the salivary gland adenoid cystic carcinoma (ACC). In this study, we aimed to clarify the function of Pim-1 in ACC in vitro. Meanwhile, we measured the levels of Pim-1 and RUNX3 in the ACC tissues. The correlations between Pim-1/RUNX3 levels and clinical parameters were also analyzed.MethodsSACC-83 and SACC-LM cells were transfected with the Pim-1 siRNA. Pim-1 mRNA and protein expression were measured using real-time PCR and immnuoblot, respectively. Cell proliferation was analyzed by CCK-8 assay. Cell cycle, apoptosis, and mitochondrial membrane potential were detected by flow cytometry. Effects of Pim-1 on cells’ invasion were evaluated by transwell migration assay. Pim-1 and RUNX3 levels in ACC tissues were examined by immunohistochemistry.ResultsPim-1 siRNA reduces cell proliferation, induces apoptosis, causes cell cycle arrest through cell cycle related proteins (Cyclin D1 and CDK4), mitochondrial depolarization, and decreases invasive ability in SACC-83 and SACC-LM cells. Pim-1 and RUNX3 levels are significantly relevant and associated with T-stage and nerve invasion in the ACC tissues.ConclusionsThis study demonstrates the oncogenic role of Pim-1 in ACC. The findings also suggest that Pim-1 may serve as a neoteric therapeutic target and potential prognostic marker for ACC cancer.
Highlights
Pim-1 (Provirus integration site for Moloney murine leukemia virus 1) belongs to the Ser/Thr kinase family and plays a pivotal role in occurrence and development of oncogenesis
Tissue specimens Fifty-four patients with histopathologically proven salivary gland adenoid cystic carcinoma (ACC) in Zhejiang Cancer Hospital between July 2006 and July 2010 were included for this study
Effect of the Pim-1 small interfering RNAs (siRNAs) on the Pim-1 level SACC-83 and SACC-LM cells were divided into three groups including blank, control siRNA, and Pim-1 siRNA groups
Summary
Pim-1 (Provirus integration site for Moloney murine leukemia virus 1) belongs to the Ser/Thr kinase family and plays a pivotal role in occurrence and development of oncogenesis. Recent studies have demonstrated that Pim-1 phosphorylates RUNX3 and alters its subcellular localization. Few studies have concerned the implications of Pim-1 in the salivary gland adenoid cystic carcinoma (ACC). We aimed to clarify the function of Pim-1 in ACC in vitro. We measured the levels of Pim-1 and RUNX3 in the ACC tissues. The correlations between Pim-1/RUNX3 levels and clinical parameters were analyzed. Salivary gland adenoid cystic carcinoma (ACC) accounts for approximately 10% of all epithelial salivary tumors. Clinical characteristics of ACC include high aggressive to nerve and vessel, high rate of recurrence, and frequent metastasis to lung. The 5-year survival rate of patients with highly metastatic ACC is less than 20%. The interaction of oncogenes and tumor suppressor genes is involved in the development of ACC.
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