Xu Jiajie, Zhu Xin, Li Qingling, Chen Chao, Guo Zhenying, Tan Zhuo, Zheng Chuanming, Ge Minghua
1Department of Head and Neck Surgery, Zhejiang Cancer Hospital, No. 38 Guangji Road, Hangzhou, 310022 Zhejiang China.
2Zhejiang Cancer Research Institute, Hangzhou, 310022 China.
Cancer Cell Int. 2018 Feb 20;18:22. doi: 10.1186/s12935-018-0518-y. eCollection 2018.
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.
A 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.
After 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.
PIM1 is multifunctional in ACC-M cells and it serves as a neoteric therapeutic target and potential prognostic marker for SACC patients.
越来越多的证据表明，PIM1是一种潜在的预后标志物和癌症治疗靶点，但其在涎腺腺样囊性癌（SACC）中的精确作用机制仍有待确定。本研究旨在阐明PIM1在SACC细胞和肿瘤组织进展中的预后及作用机制。
用靶向PIM1基因的shRNA质粒转染SACC细胞系（ACC-M）。通过定量实时PCR和蛋白质印迹法检测PIM1、RUNX3和p21的表达水平。使用免疫荧光评估RUNX3和p21蛋白的亚细胞转位，并使用流式细胞术对细胞周期阶段进行定量分析。对97例SACC患者的临床病理特征和生存结果进行回顾性分析。
ACC-M细胞中PIM1下调后，RUNX3和p21蛋白从细胞质转位至细胞核，p21表达降低，G0/G1期细胞增加。PIM1和RUNX3水平呈现明显的协方差。PIM1与SACC组织中的T分期、淋巴结受累、神经侵犯和远处转移相关。PIM1水平低的患者比PIM1水平高的患者预后更好。
PIM1在ACC-M细胞中具有多种功能，它是SACC患者的新型治疗靶点和潜在的预后标志物。
