OBJECTIVES: To explore the expression of hexokinase 2 (HK2) in colorectal cancer (CRC) and its possible mechanisms for regulating tumor cell behaviors and tumor immune microenvironment. METHODS: We analyzed HK2 expression in CRC and its impact on patient prognosis and tumor immune microenvironment using public databases. HK2 expression was also examined in 8 CRC and paired adjacent tissues using immunohistochemistry, Western blotting and RT-qPCR. In cultured CRC cell lines CT26 and HCT116 with low HK2 expression, the effects of lentivirus-mediated HK2 overexpression and JAK/STAT3 inhibitors on cell proliferation, migration, and invasion were assessed using CCK-8 assay, colony formation assay and Transwell assay and in a subcutaneous tumor-bearing mouse model; the changes were also observed in MC38 and CACO2 cells with high HK2 expressions following treatment with HK2 inhibitor 3-BP. Western blotting was performed to verify the relationship between HK2 and JAK/STAT signaling pathway protein expressions. RESULTS: Informatics analyses suggested that HK2 expression was significantly higher in CRC tissues than in adjacent tissues (P<0.001), and patients with high HK2 expressions had worse prognosis (P=0.09). In the 8 clinical CRC tissues, HK2 expressions were significantly higher in the tumor tissues than in the adjacent tissues (P<0.01). In CT26 and HCT116 cells, HK2 overexpression significantly enhanced cell proliferation, migration and invasion, while in HK2-overexpressing MC38 and CACO2 cells, inhibiting HK2 with 3-BP strongly suppressed these changes. HK2 overexpression promoted STAT3 phosphorylation, and JAK/STAT3 inhibitors effectively suppressed tumor cell proliferation, migration and invasion. TIMER and MCPcounter analyses indicated correlations between HK2 and immune cells, and TCGA and GEO analyses suggested significant positive correlations between HK2 and the immune checkpoints including PDCD1. CONCLUSIONS HK2 is upregulated in CRC to promote tumor cell proliferation, migration and invasion possibly by activating the JAK-STAT signaling pathway and modulating tumor immune microenvironment.
Humans ; Colorectal Neoplasms/metabolism* ; Cell Proliferation ; Hexokinase/genetics* ; Tumor Microenvironment ; Cell Movement ; Signal Transduction ; Animals ; STAT3 Transcription Factor/metabolism* ; Mice ; Neoplasm Invasiveness ; Cell Line, Tumor ; Janus Kinases/metabolism* ; HCT116 Cells ; Caco-2 Cells

Objective:To investigate the current status and problems of the development of dental technology specialty in higher vocational colleges in China, and to provide a reference for the establishment of national standards for vocational education on dental technology and the development of high-quality higher vocational education.Methods:We selected 54 higher vocational colleges in eastern, central, and western China offering dental technology programs by stratified random sampling to survey the specialty development situation using a questionnaire. Data were analyzed using the independent samples t test, one-way analysis of variance, or chi-square test with the use of SPSS 18.0. Results:Among the surveyed colleges, the average annual enrollment scale in recent three years was 6 415 students, with the largest enrollment in western regions, accounting for 47.39%. In terms of teaching faculty, there were differences in educational attainment, professional title structure, vocational qualification, and professional background between different regions ( P<0.05). Regarding training conditions, only 26.42% and 3.77% of colleges were equipped with virtual simulation training rooms and dental materials training rooms, respectively; and 18.52% and 22.22% of colleges were equipped with chairside repair systems and virtual simulation software, respectively. Conclusions:Regional imbalances exist in the development of dental technology specialty in higher vocational colleges in China. The overall level of teaching staff, practical training conditions, and curriculum construction need to be improved.