Pim-1 is an oncogene and has been proved to play pivotal role in proliferation, apoptosis and angiogenesis. Thyroid cancer represents the most common malignancy in the endocrine system and displays a marked increase in the incidence in recent years. Papillary thyroid cancer (PTC) is among the most frequent thyroid malignancies and accounts for more than 85%. Therefore, it is worthwhile to discuss the function of Pim-1 in the development and progression of PTC.
Gene set enrichment analysis (GSEA) of Pim-1 in the PTC was performed on the TCGA databases. 177 PTC paraffin blocks were selected to make the tissue microarrays and the levels of Pim-1 protein was investigated by immunohistochemistry. Meanwhile, one of the Pim-1 kinase inhibitor, SGI-1776, was used to evaluate the function of Pim-1 on the PTC cell BCPAP and TPC-1. CCK-8 and colony formation assay was carried out to measure the cell proliferation. Apoptosis rate and migration capacity were determined by flow cytometry and wound-healing methods respectively.
GSEA results revealed that Pim-1 expression was significantly associated with the immune system of PTC. IHC result showed that Pim-1 was overexpressed in the PTC tissues compared with normal adjacent tissues. Meanwhile, Pim-1 had a significant relationship with the T-stage, lymph node involvement, capsule invasion and gender. Female patients and patients with higher T-stage, positive lymph node involvement, positive capsule invasion have a higher Pim-1 level. After SGI-1776 treatment, Pim-1 expressions were obviously downregulated in both BCPAP and TPC-1. Decreased Pim-1 led to the proliferation depression, apoptosis rate elevation and the migration capacity reduction in both cell lines.
Taken together, our current data showed the important role of Pim-1 in the tumorigenesis of PTC. High Pim-1 level linked to immune status and aggressive malignant behavior of PTC. It was also suggested that PIM-1 kinase might be a novel molecular biomarker of PTC.
Clinical trial identification
Legal entity responsible for the study
Zhejiang Province Natural Science Foundation of China.
All authors have declared no conflicts of interest.