探討Nucleobindin-2對人類肝癌細胞的影響

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標題:	探討Nucleobindin-2對人類肝癌細胞的影響 To investigate the effect of Nucleobindin-2 on human hepatocellular carcinoma cells 癌症在十大死因之中長年位居第1，根據 2018 年統計肝癌在全世界癌症死亡率排行第4，並且在台灣位於癌症死亡率高居第2位。然而肝癌在各種治療上，經常發生抗藥性、復發率高及預後治療不佳的結果，因此開發肝癌新治療目標是目前迫切需要被研究的主題。近年來在許多癌症組織都觀察到有內質網壓力 (Endoplasmic Reticulum Stress,ER Stress) 及內質網壓力所誘導的相關基因有過量表現的情形。先前我們的研究發現內質網壓力可以誘導肝癌細胞過量表現 Nucleobindin-2 (NUCB-2)，當使用NUCB-2 shRNA時可以明顯在內質網壓力下降低NUCB-2 mRNA的表現。此外先前分析發現NUCB-2 promoter具有XBP-1蛋白結合位置，進一步以IRE-1 抑制劑抑制下游基因 XBP-1 時，結果顯示IRE-1 抑制劑在內質網壓力下，會降低Huh-7細胞中 NUCB-2 mRNA表現量。另外，我們利用生物資訊資料庫分析發現肝癌組織有 NUCB-2 過量表現的情況，進一步的以UALCAN及cBioPortal 資料庫分析，結果顯示NUCB-2的表現與內質網壓力相關基因有共同表現的情形。此外以Venny 2.0及DAVID生物資訊分析，結果顯示NUCB-2可能參與細胞週期相關的訊息傳遞路徑。進一步，我們也分析了 120 組臨床肝癌檢體，結果顯示肝癌檢體有內質網壓力及NUCB-2過量表現情形，在 B 型肝炎病毒的肝癌組織中NUCB-2 呈現較高的表現量情形。未來我們會繼續探討在ER Stress下誘導 NUCB-2 表現的機制與其在肝癌細胞所扮演的角色，我們期望NUCB-2位來能當作新藥開發的目標或生物標記的功能。 Cancer ranks first among the top ten causes of death for many years. According to 2018 statistics, liver cancer ranks fourth in the world for cancer mortality, and ranks second in Taiwan for cancer mortality. However, liver cancer often has drug resistance, high recurrence rate, and poor prognosis in various treatments. Therefore, the development of new treatment strategies for liver cancer is an urgently issue. Previous study indicated that induction of endoplasmic reticulum stress (ER stress) and ER stress-associated genes were observed in many cancer tissues. Our previous study found that overexpression of nucleobindin-2 (NUCB-2) was induced by ER stress in Huh-7 and HepG2 cell lines. Furthermore, downregulation of NUCB-2 expression was used by NUCB-2 shRNA in response to ER stress. Previous analysis indicated that NUCB-2 promoter has a binding site for XBP-1 protein. NUCB-2 expression was significantly decreased by using XBP-1 upstream regulator inhibitor (4u8c). In addition, the relationship between ER stress and NUCB-2 expreesion in liver caner tissues was determined by using Bioinformatics databases. ER stress and NUCB-2 overexpression were observed in hepatocellular carcinoma (HCC) through Bioinformatics analysis. Further analysis by UALCAN and cBioPortal database showed that the co-expression of NUCB-2 and ER stress-related genes was observed in HCC. In addition, HCC clinical specimens of 120 pairs patients was analyzed by real-time PCR for NUCB-2 and GRP78 expression. The result indicated that NUCB-2 overexpression and ER stresss induction were found in HCC clinical specimens. NUCB-2 presents a higher level of expression in hepatitis B virus liver cancer tissues. In the future, we will continue to investigate the mechanism of NUCB-2 expression by ER stress and its role in liver cancer cells. We hope the NUCB-2 can be used as a target for new drug development or as a biomarker in the future.
作者:	曹秀萍
貢獻者:	生物科技系洪瑞祥
關鍵字:	肝癌內質網壓力 NUCB-2 GRP78 NUCB-2 shRNA 生物資訊 HCC ER Stress NUCB-2 GRP78 NUCB-2 shRNA Bioinformatics
日期:	2020
上傳時間:	2022-10-21 10:32:48 (UTC+8)
關聯:	電子全文公開日期：2025-08-27 學年度：108， 81頁
顯示於類別:	[生物科技系(所)] 博碩士論文

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