Abstract
BackgroundIncreasing evidence indicates that PIM1 is a potential prognostic marker and target for cancer treatment but its precise mechanisms of action remain to be determined in salivary adenoid cystic carcinoma (SACC). This study aims to decipher the prognostic and mechanistic role of PIM1 in progression of SACC cells and tumor tissues.MethodsA SACC cell line (ACC-M) was transfected with shRNA plasmids targeting the PIM1 gene. The expression levels of PIM1, RUNX3 and p21 were measured by quantitative real-time PCR and western blot. Subcellular translocalization of RUNX3 and p21 proteins was assessed using immunofluorescence, and cell cycle phase was quantified using flow cytometry. A total of 97 SACC patients were retrospectively analyzed by clinicopathologic characteristics and survival outcomes.ResultsAfter down-regulation of PIM1 in ACC-M cells, RUNX3 and p21 proteins were translocated from cytoplasm to nucleus, with a decrease of p21 expression and increase of G0/G1 phase cells. PIM1 and RUNX3 levels show a distinct covariance. PIM1 is associated with T-status, lymph node involvement, nerve invasion, and distant metastasis in SACC tissues. Patients with low PIM1 level had a better outcome than those with higher PIM1 level.ConclusionsPIM1 is multifunctional in ACC-M cells and it serves as a neoteric therapeutic target and potential prognostic marker for SACC patients.
Highlights
Increasing evidence indicates that PIM1 is a potential prognostic marker and target for cancer treatment but its precise mechanisms of action remain to be determined in salivary adenoid cystic carcinoma (SACC)
Downregulation of PIM1 in Adenoid cystic carcinoma (ACC)‐M cells treated with pGPU6/green fluorescent protein (GFP)/Neo‐short hairpin RNA (shRNA) In this study, we used LipofectamineTM 2000 reagent to optimize the transfection condition
We found that the total transfection rate was more than 70% after transfected for 48 h. Both PIM1 mRNA and protein levels were significantly decreased in ACC-M cells after shRNA transfection
Summary
Increasing evidence indicates that PIM1 is a potential prognostic marker and target for cancer treatment but its precise mechanisms of action remain to be determined in salivary adenoid cystic carcinoma (SACC). This study aims to decipher the prognostic and mechanistic role of PIM1 in progression of SACC cells and tumor tissues. Salivary adenoid cystic carcinoma (SACC) is characterized by highly aggressive nerve and vessel infiltration, high rate of recurrence, and frequent metastasis to lung [2]. In several human cancer types, including T-and B-cell leukemia and lymphomas, the overexpression of PIM1 inhibits apoptosis, promotes proliferation, and prevents differentiation and maturation [6]. PIM1 kinase promotes cell cycle progression and proliferation
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