干擾素誘導四肽重複蛋白5 (IFIT5) 在神經膠質母細胞瘤的細胞增殖與移動所扮演的角色

Abstract

多型性神經膠質母細胞瘤 (Glioblastoma multiforme，GBM) 是成人最常見且最為惡性的原發性腦癌，以高復發率和低5年生存率著稱，目前還沒有發現有效的治療方法。現在主要的治療方式是以手術切除合併化療和放射治療。之前研究表明，神經膠質母細胞瘤之癌幹細胞 (Glioblastoma stem cells, GSCs) ，與腫瘤之增生、轉移、抗藥性及預後復發有關。若能針對調控神經膠質母細胞瘤之癌幹細胞(GSCs)的生長維持機制，找出抑制腫瘤生長的方法，將會是治療多型性神經膠質母細胞瘤(GBM)的新方法。IFIT5 (Interferon-induced protein with tetratricopeptide repeats 5)是IFIT protein家族的一員，為細胞在病毒防禦上的重要蛋白質。IFIT5在細胞表面肌動蛋白絲(actin)豐富處表現。實驗室之前的研究使用OncoLnc分析TCGA資料庫發現不論在神經膠質母細胞瘤或其他低程度神經膠質瘤中，高表現IFIT5的患者有較低的整體存活率。為研究IFIT5在神經膠質母細胞瘤的功能，本實驗利用U87-MG此種多型性神經膠質母細胞瘤及其過度表現IFIT5的細胞株發現，過度表現IFIT5會抑制多型性神經膠質母細胞瘤及其癌幹細胞的增殖和移動能力。

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults, known for its high recurrence and low 5-year survival rate. At present, the main treatment of GBM is surgical resection combined with chemotherapy and radiation therapy, however, no treatment has yet been shown to be effective. Studies have pointed out that one type of cancer cells, glioblastoma cancer stem cells (GSCs), are related to tumor proliferation, metastasis, drug resistance and prognostic recurrence. If the growth and maintenance mechanism of GSCs in glioblastoma can be regulated and the method to inhibit tumor growth can be found, it will be a new method for the treatment of GBM. Interferon-induced protein with tetratricopeptide repeats 5 (IFIT5) is a member of the IFIT protein family and is an important protein for cell defense against viruses. IFIT5 has been known to concentrated in actin-rich protrusions from the apical cell surface. Our previous study used OncoLnc database analyzing engine and found that patients with higher expression of IFIT5 have better overall survival in both GBM and lower grade glioma. In order to study the function of IFIT5 in GBM, we used U87-MG to establish IFIT5 stably expressing cell line and found that overexpression of IFIT5 downregulates cell proliferation and migration in GBM and GSCs.