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ID: 419 (Conflict of Interest: K)

Die potentielle onkogene Rolle von Interferon-induziertem Protein mit Tetratricopeptid-Repeats 3 (IFIT3) in PDAC

Z.Wang, J.Qin, J.Zhao, J.Li, M.Popp, F.Popp, C. J.Bruns, Y.Zhao
Uniklinik Köln, Köln

Einleitung

Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is one of  interferon stimulated genes, which shows various antiviral and pro-inflammatory functions. Recently, IFIT3 was also reported to be involved in tumor progression. Our previous studies showed that IFIT3 was upregulated in high-metastatic pancreatic ductal adenocarcinoma (PDAC) cell line L3.6pl as compared to its origin FG cell line. We found that high expression of IFIT3 was related with poor survival in those PDAC patients who received chemotherapy. Further studies on oncogenic role of IFIT3 in PDAC are investigated.

Material und Methoden

IFIT3-overexpression (IFIT3-OE) cells were established with 3rd generation lentiviral system and IFIT3-knockout (IFIT3-KO) cells were established with CRISPR/Cas9 nickase system. Cell apoptosis, chemotherapy-resistance and proliferation capacity of IFIT3 in modified cells were investigated. In addition, recombinant IFIT3 protein (re-IFIT3) was applied for rescue experiments. 

Ergebnisse

IFIT3 positive cells were enriched after gemcitabine treatment on PDAC cell lines. Further in vitro experiments showed that IFIT3-OE cells were more resistant to chemotherapy and re-IFIT3 protein decreased apoptosis of IFIT3-KO cells induced by gemcitabine treatment. Immunoprecipitation showed interaction between IFIT3 and IFIT2, while IFIT2 has been reported to induce mitochondrial associated apoptosis. Furthermore, the addition of re-IFIT3 protein in IFIT3-KO cells showed increased mitotic rate and higher proliferation. 

Schlussfolgerung

These data demonstrated that IFIT3 can reduce cell apoptosis and contribute to chemotherapy resistance. Besides, IFIT3 showed an increased capacity on tumor cell proliferation. The detailed mechanism of the oncogenic role of IFIT3 in PDAC willbe explored.