在先前計畫我們利用大數據分析方法來探討具有治療或生物標記的基因，分析結果顯示Nucleobindin-2 (NUCB-2)在肝癌有過量表現的情形，而高NUCB-2表現的肝癌病人呈現較差的預後率，在生物資訊分析結果也顯示NUCB-2過量表現對於亞洲男性病毒型肝癌患者其存活率最低。在計畫中我們發現內質網壓力透過XBP-1訊息傳遞路徑來調控NUCB-2的表現，然而NUCB-2在腫瘤細胞過量表的機制和所扮演的角色尚未釐清。我們進一步分析發現鈣離子及KLF-4可能參與調控內質網壓力誘導NUCB-2表現的機制。此外也觀察到在內質網壓力下NUCB-2有入核的情形及降低NUCB-2表現時會改變細胞膜組成比例。因此在本計畫中我們想要進一步的探討NUCB-2的角色。在本計畫中我們將完成分析內下列三主題(1)探討鈣離子及KLF-4對內質網壓力誘導NUCB-2表現的關係。(2)探討NUCB-2入核對基因表現的影響及利用coexpression及MetaCore來分析NUCB-2可能參與的訊息傳遞路徑。(3)分析NUCB-2在細胞膜組成比例恆定機制所扮演的角色。計畫的結果我們希望這樣的結果可以提供一個重要的資訊來應用在腫瘤治療、內質網壓力相關疾病及疾病檢驗方面，最後希望能給這一群高NUCB-2表現的病人提供一個精準醫療的治療策略。 In our previous project, we try to develop a novel biomarker or therapeutic target gene in HCC by using big data analysis. The result indicated that overexpression of NUCB-2 was observed in HCC by using bioinformatics analysis. The HCC patients with NUCB-2 overexpression are associated with poor prognosis. The results of bioinformatics analysis also indicated that overexpression of NUCB-2 showed the lowest survival rate for HCC patients of Asian male with viral infection. Our results also indicated that induction of NUCB-2 overexpression was through XBP-1 signaling pathway during endoplasmic reticulum stress (ER stress). However, the role and mechanism of NUCB-2 overexpression in HCC and ER stress is still unclear. We further analyzed the mechanism that calcium and KLF-4 may be involved in regulation of NUCB-2 expression in response to ER stress. In addition, nuclear translocation of NUCB-2 and modification of cell membrane composition were observed during ER stress. Therefore, we try to investigate a novel of NUCB-2 in HCC in this project. In this project, we will focus on three aims: (1) To investigate the relationship between calcium ion and KLF-4 on NUCB-2 expression during ER stress. (2) To determine the effect of nuclear translocation of NUCB-2 on gene expression, and used coexpression and MetaCore system to analyze the relationship between NUCB-2 and intracellular signaling pathways. (3) To analyze the role of NUCB-2 in maintaining a constant ratio of cell membrane composition. In the results of this project, we hope that it can provide important information for application in cancer treatment, ER stress-related diseases and disease diagnosis. Finally, we hope to provide a precise medical treatment strategy for this group of patients with high NUCB-2 expression.
