As a oncogene, Pim-1 has been proved to play key role in proliferation, apoptosis and angiogenesis. Thyroid cancer represents the most common malignancy in the endocrine system, and a marked increase in the incidence has occurred in recent years. Among them, papillary thyroid carcinoma (PTC) is the most common form. So it is worthwhile to discuss the function of Pim-1 in the development and progression of PTC.
34 PTC patients were selected to investigate the levels of Pim-1, HIF-1α and GAB1 protein by IHC. After hypoxia treatment for 24h, Westernblot was carried out to detect the Pim-1, HIF-1α and GAB1 in the PTC cell BCPAP and TPC-1. BCPAB was trasfected with GAB1 shRNA and Full-length vector to achieve GAB1 knockdown and overexpression. CCK-8 assay was used to measure the ell proliferation. The migration and invasion capacity were tested by wound-healing and transwell methods respectively.
Both Pim-1 and HIF-1α were overexpressed in the PTC tissues and Pim-1 levels were significant correlated with HIF-1α. Meanwhile, Pim-1 had a significant relationship with the tumor number - patients with multiple tumor have a higher Pim-1 level than that have solitary tumor and HIF-1α showed a significant correlation with patients’ age. After bioinformatics screen, we found that there were 4 hypoxia response elements (HRE) in the Pim-1 promoter area, which suggested HIF-1α could transcriptional regulate Pim-1 directly. Moreover, hypoxia could signifcantly drive HIF-1α and Pim-1 elevation in both BCPAP and TPC-1. GAB1 was found to express higher in PTC tissues than that in the adjacent normal tissues and GAB1 level was significant associated with the tumor size. Morover, Pim-1 expression was significantly decrease and increase after GBA1 knockdown and overexpression in BCPAP. Meanwhile, GAB1 did not affect the cell viability but exerted a strong effect on the migration and invasion capacity of BCPAP. However, there was no change in GAB1 expression after hypoxia treatment in both BCPAP and TPC-1.
Taken together, our current data showed the important role of Pim-1 in the PTC. It also can be deduced that both HIF-1α and GAB1 are involved in the upstream regulation of Pim-1, but the detailed mechanism are different, which depended on the different tumor microenvironment.
Clinical trial identification
Legal entity responsible for the study
Zhejiang Cancer Hospital.
National Natural Science Foundation of China.
All authors have declared no conflicts of interest.