跳到主要內容

臺灣博碩士論文加值系統

(3.231.230.177) 您好!臺灣時間:2021/07/28 15:08
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:曹秀萍
研究生(外文):TSAO,HSIU-PING
論文名稱:探討Nucleobindin-2對人類肝癌細胞的影響
論文名稱(外文):To investigate the effect of Nucleobindin-2 on human hepatocellular carcinoma cells
指導教授:洪瑞祥
指導教授(外文):HONG,HUI-HSIANG
口試委員:陳品晟鄧燕妮洪瑞祥
口試委員(外文):CHEN,PIN-SHERNTENG,YEN-NIHONG,HUI-HSIANG
口試日期:2020-07-21
學位類別:碩士
校院名稱:嘉南藥理大學
系所名稱:生物科技系
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:81
中文關鍵詞:肝癌內質網壓力NUCB-2GRP78NUCB-2 shRNA生物資訊
外文關鍵詞:HCCER StressNUCB-2GRP78NUCB-2 shRNABioinformatics
相關次數:
  • 被引用被引用:0
  • 點閱點閱:30
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
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.
摘要……………………………………………………………………………..I
Abstract……………………………………………………………………………III
目錄…………………………………………………………………………...IV
圖目錄……………………………………………………………………....VIII
英文縮寫對照表………………………………………………………………XI
第一章 緒論…………………………………………………………………...1
1.1肝癌 (Hepatocellular carcinoma,HCC)…………………...…………….1
1.1.1肝癌細胞之危險因子............................................................................2
1.2內質網……………………………………………………………….…...7
1.2.1葡萄糖調節蛋白 (78-kDa Glucose Regulated Protein,GRP78)…….8
1.3內質網壓力誘導相關蛋白反應機制..........................................................9
1.4未摺疊蛋白質反應 (Unfold Protein Response)………...………………10
1.5 內質網壓力與肝癌之關聯性..................................................................11
1.6 NUCB-2 (Nucleobindin-2)........................................................................12
1.7生物資訊 (Bioinformatics)……………………………………………...13
1.8研究動機....................................................................................................14
第二章 材料與方法...........................................................................................15
2.1 生物資訊網站..........................................................................................15
2.1.1 Oncomine Comprehensive Panel..........................................................15
2.1.2 Kaplan Meier plotter.............................................................................15
2.1.3 STRING................................................................................................15
2.1.4 The Human Protein Atlas......................................................................15
2.1.5 GEPIA..................................................................................................16
2.2材料............................................................................................................16
2.2.1藥品......................................................................................................16
2.2.2儀器......................................................................................................19
2.3細胞培養....................................................................................................19
2.3.1解凍細胞..............................................................................................19
2.3.2細胞繼代培養......................................................................................20
2.3.3計數細胞..............................................................................................19
2.3.4冷凍細胞..............................................................................................21
2.4西方墨點法 (Western blot).......................................................................21
2.4.1細胞內蛋白質萃取..............................................................................21
2.4.2蛋白質定量..........................................................................................21
2.4.3配置膠體..............................................................................................22
2.4.4蛋白質電泳..........................................................................................23
2.4.5蛋白質轉漬..........................................................................................24
2.4.6免疫墨點法..........................................................................................25
2.5細菌培養..………………………………………………..………………26
2.5.1液態培養條件…..…………………………………………………....26
2.6菌液定量………………………………………………………………...26
2.6.1菌液定量之過程……….…………………………………………...26
2.7質體DNA純化 (Purification of plasmid DNA)………………………...27
2.7.1質體DNA純化之過程…………………………………………….....27
2.7.2 DNA濃度與純度測定…………………………………………….....28
2.8 細胞轉染……………………………………………………..…………28
2.8.1 293T 人類腎上皮細胞系轉染………………………………….....28
2.9病毒轉染………..………………………………………………………29
2.9.1 Huh-7 病毒轉染…………………………………………..…………29
2.10抽取細胞培養 total RNA (Isolate total RNA)........................................30
2.11反轉錄聚合酶連鎖反應 (RT-PCR)........................................................30
2.12即時聚合酶連鎖反應 (Real-Time PCR)................................................31
2.13 Reverse transcription 120組人體臨床肝癌檢體………………..……..32
2.13.1 Reverse transcription 120組人體臨床肝癌檢體……………..…….32
2.13.2即時聚合酶連鎖反應 (Real-time PCR)……………………………33
2.13.3患者與組織樣本…..…………………………………….………….34
2.13.4 Graphpad prism 5之統計分析……………………………………...34
第三章 結果.......................................................................................................35
3.1生物資訊分析 NUCB-2 基因在肝癌的表現情形.................................35
3.2內質網壓力對NUCB-2的影響................................................................36
3.3抑制 NUCB-2 對 UPR 路徑的影響.....................................................36
3.4抑制 XBP-1 基因對 NUCB-2 表達的影響..........................................36
3.5分析NUCB-1與NUCB-2對肝癌患者存活率影響.................................37
3.6利用 Kaplan Meier plotter 資料庫分析NUCB-2表現對肝癌患者之存活率影響.............................................................................................................37
3.7利用 cBioPortal 搜尋 NUCB-2 在肝癌及乳癌之 Co-expression….38
3.8探討 120 組人體臨床肝癌檢體的 GRP78 及 NUCB-2之表現量….38
3.9根據肝癌臨床患者臨床病理特徵進行GRP78與NUCB-分析與探討..39
3.9.1 針對性別分析NUCB-2在肝癌中之影響…………………………..39
3.9.2 針對病毒感染分析 NUCB-2 在肝癌中之影響………………...…39
3.9.3 針對肝硬化分析 NUCB-2 在肝癌中之影響……………………...39
3.9.4針對腫瘤大小分析 NUCB-2 在肝癌中之影響…………………...40
3.9.5 分析人類肝癌檢體 NUCB-2 存活率表現………………………...40
第四章 討論.......................................................................................................41
第五章 結論.......................................................................................................45
第六章 參考文獻...............................................................................................47
圖表……………………………………..……………………………………...54

1.Schraml C, Kaufmann S, Rempp H,et al. Imaging of HCC-Current State of the Art. Diagnostics. 2015;5(4):513-45.
2.El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264-1273.
3.Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329-338.
4.Sukowati CH, Rosso N, Crocè LS, Tiribelli C. Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma. World J Hepatol. 2010;2(3):114-126.
5.Chen CJ, Yu MW, Liaw YF. Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997;12(9-10):S294-308.
6.Su IJ, Hsieh WC, Tsai HW, Wu HC. Chemoprevention and novel therapy for hepatocellular carcinoma associated with chronic hepatitis B virus infection. Hepatobiliary Surg Nutr. 2013;2(1):37-9.
7.Zhang X, Hou J, Lu M. Regulation of hepatitis B virus replication by epigenetic mechanisms and microRNAs. Front Genet. 2013;4:202.
8.Tropberger P, Mercier A, Robinson M, Zhong W, Ganem DE, Holdorf M. Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation. Proc Natl Acad Sci U S A. 2015;112(42) :6995-7023.
9.Rodriguez-Frias F, Buti M, Tabernero D, Homs M. Quasispecies structure, cornerstone of hepatitis B virus infection: mass sequencing approach. World J Gastroenterol. 2013;19(41).
10.DiMattia MA, Watts NR, Stahl SJ,et al. Antigenic switching of hepatitis B virus by alternative dimerization of the capsid protein. Structure. 2013;21(1) :133-142.
11.Chen M, Sällberg M, Hughes J,et al. Immune tolerance split between hepatitis B virus precore and core proteins. J Virol. 2005;79(5):3016-27.
12.Milich DR. Influence of T-helper cell subsets and crossregulation in hepatitis B virus infection. J Viral Hepat. 1997;4 Suppl 2:48-59.
13.Zemel R, Issachar A, Tur-Kaspa R. The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma. Clin Liver Dis. 2011;15(2):261-79.
14.Slagle BL, Lee TH, Medina D, Finegold MJ, Butel JS. Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene. Mol Carcinog. 1996;15(4):261-9.
15.Takada S, Tsuchida N, Kobayashi M, Koike K. Disruption of the function of tumor-suppressor gene p53 by the hepatitis B virus X protein and hepatocarcinogenesis. J Cancer Res Clin Oncol. 1995;121(9-10):593-601.
16.Li G, De Clercq E. Current therapy for chronic hepatitis C: The role of direct-acting antivirals. Antiviral Res. 2017;142:83-122.
17.Moradpour D, Penin F. Hepatitis C virus proteins: from structure to function. Curr Top Microbiol Immunol. 2013;369:113-42.
18.Messina JP, Humphreys I, Flaxman A,et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77-87.
19.Zeisel MB, Felmlee DJ, Baumert TF. Hepatitis C virus entry. Curr Top Microbiol Immunol. 2013;369:87-112.
20.Von Hahn T, Rice CM. Hepatitis C virus entry. J Biol Chem. 2008;283(7):3689-93.
21.Rehermann B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J Clin Invest. 2009;119(7):1745-54.
22.Thompson KJ, Humphries JR, Niemeyer DJ, Sindram D, McKillop IH. The effect of alcohol on Sirt1 expression and function in animal and human models of hepatocellular carcinoma (HCC). Adv Exp Med Biol. 2015;815:361-73.
23.Zakhari S. Overview: how is alcohol metabolized by the body? Alcohol Res Health. 2006;29(4):245-54.
24.Howard J. Edenberg,Tatiana Foroud. Genetics and alcoholism. Nat Rev Gastroenterol Hepatol. 2013;10(8): 487-494.
25.Uomori T, Horimoto Y, Mogushi K, Matsuoka J, Saito M. Relationship between alcohol metabolism and chemotherapy-induced emetic events in breast cancer patients. Breast Cancer. 2017;24(5):702-707.
26.Bosron WF, Ehrig T, Li TK. Genetic factors in alcohol metabolism and alcoholism. Semin Liver Dis. 1993;13(2):126-35.
27.Regina M. Santella, Hui-Chen Wu. Environmental Exposures and Hepatocellular Carcinoma. J Clin Transl Hepatol. 2013; 1(2): 138-143.
28.Raphael JF Felizardo, Niels OS Câmara. Hepatocellular carcinoma and food contamination: Aflatoxins and ochratoxin A as great prompter. World J Gastroenterol. 2013;19(24): 3723-3725.
29.Rieswijk L, Claessen SM, Bekers O, et al. Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016;350-352:31-9.
30.Stettler PM, Sengstag C. Liver carcinogen aflatoxin B1 as an inducer of mitotic recombination in a human cell line. Mol Carcinog. 2001;31(3):125-38.
31.Groopman JD, Cain LG, Kensler TW. Aflatoxin exposure in human populations: measurements and relationship to cancer. Crit Rev Toxicol. 1988;19(2):113-45.
32.Peers F, Bosch X, Kaldor J, Linsell A, Pluijmen M. Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland. Int J Cancer. 1987;39(5):545-53.
33.Chu YJ, Yang HI, Wu HC. Aflatoxin B1 exposure increases the risk of hepatocellular carcinoma associated with hepatitis C virus infection or alcohol consumption. Eur J Cancer. 2018;94:37-46.
34.Chu YJ, Yang HI, Wu HC. Aflatoxin B1 exposure increases the risk of cirrhosis and hepatocellular carcinoma in chronic hepatitis B virus carriers. Int J Cancer. 2017;141(4):711-720.
35.Wild CP, Turner PC. The toxicology of aflatoxins as a basis for public health decisions. Mutagenesis. 2002;17(6):471-81.
36.Hussain SP, Schwank J, Staib F, Wang XW, Harris CC. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene. 2007;26(15):2166-76.
37.Ammerpohl O, Pratschke J, Schafmayer C, et al. Distinct DNA methylation patterns in cirrhotic liver and hepatocellular carcinoma. Int J Cancer. 2012;130(6):1319-28.
38.Ozturk M. Genetic aspects of hepatocellular carcinogenesis. Semin Liver Dis. 1999;19(3):235-42.
39.Schlaeger C, Longerich T, Schiller C, et al. Etiology-dependent molecular mechanisms in human hepatocarcinogenesis. Hepatology. 2008;47(2):511-20.
40.Moinzadeh P, Breuhahn K, Stützer H, Schirmacher P. Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade--results of an explorative CGH meta-analysis. Br J Cancer. 2005;92(5):935-
41.Ding SF, Habib NA. Loss of heterozygosity in liver tumours. J Hepatol. 1995;22(2):230-8.
42.Zhou YZ, Slagle BL, Donehower LA, vanTuinen P, Ledbetter DH, Butel JS. Structural analysis of a hepatitis B virus genome integrated into chromosome 17p of a human hepatocellular carcinoma. J Virol. 1988;62(11):4224-31.
43.Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994;54(18):4855-78.
44.Greenblatt MS, Feitelson MA, Zhu M, et al. Integrity of p53 in hepatitis B x antigen-positive and -negative hepatocellular carcinomas. Cancer Res. 1997;57(3):426-32.
45.Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer. 2014;14(9):581-97.
46.Palade GE, Porter KR. Studies on the endoplasmic reticulum. I. Its identification in cells in situ. J Exp Med. 1954;100(6):641-56.
47.Vishnu N, Khan MJ, Karsten F, et al. ATP increases within the lumen of the endoplasmic reticulum upon intracellular Ca2+ release. Mol Biol Cell. 2014; 25(3): 368-379.
48.Brocchieri L, Conway de Macario E, Macario AJ. hsp70 genes in the human genome: Conservation and differentiation patterns predict a widearray of overlapping and specialized functions. BMC Evol Biol. 2008;8(19). doi:10.1186/1471-2148-8-19.
49.LeeAS. GRP78 induction in cancer : therapeutic and prognostic implications. Cancer Res. 2007;67(8):3496-9.
50.Montague K, Malik B, Gray AL,et al. Endoplasmic reticulum stress in spinal and bulbar muscular atrophy:a potential target for therapy. Brain. 2014; 137(7):1894-1906.
51.Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis. 2009;14(8):996-1007.
52.Flamment M ,Hajduch E, Ferré P, Foufelle F. New insights into ER stress-induced insulin resistance. Trends Endocrinol. Metab. 2012;23(8):381-390.
53.Jackson LW, Pryor BM. Degradation of aflatoxin B1 from naturally contaminated maize using the edible fungus Pleurotus ostreatus. AMB Express. 2017;7(1):110.
54.Haeri M, MD, Knox BE. Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways: Potential for Treating Age-related Retinal Degeneration. J Ophthalmic Vis Res. 2012;7(1): 45-59.
55.Gething M-J, Sambrook J. Protein folding in the cell. Nature. 1992;355(6355):33-45.
56.Hsu SK, Chiu CC, Dahms HU, et al. Unfolded Protein Response (UPR) in Survival, Dormancy, Immunosuppression, Metastasis, and Treatments of Cancer Cells. Int J Mol Sci. 2019;20(10).
57.Olivia I. Coleman and Dirk Haller. ER Stress and the UPR in Shaping Intestinal Tissue Homeostasis and Immunity. Front Immunol. 2019; 10: 2825.
58.Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8(7):519-29.
59.Groenendyk J, Michalak M. Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol. 2005;2:381-395.
60.Bhandary B, Marahatta A, Kim H R, Chae H J. An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases. Int J Mol Sci. 2012.14(1):434-56.
61.Hotamisligil GS. Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease. Cell. 2010;140(6):900-917.
62.Liao Y, Gu F, Mao X,et al. Regulation of de novo translation of host cells by manipulation of PERK/PKR and GADD34-PP1 activity during Newcastle disease virus infection. J. Gen. Virol. 2016;97(4):867-879.
63.Coelho DS, Domingos PM. Physiological roles of regulated Ire1 dependent decay. Front Genet. 2014; 5(76).
64.Doroudgar S, Glembotski CC. ATF6 and Thrombospondin 4: The Dynamic Duo of the Adaptive Endoplasmic Reticulum Stress Response. Circ Res. 2013;112(1):9-12.
65.Zhang SX, Ma JH, Bhatta M, Fliesler SJ, Wang JJ. The unfolded protein response in retinal vascular diseases: implications and therapeutic potential beyond protein folding. Prog Retin Eye Res. 2015;45:111-131.
66.Yang MH, Wu MZ, Chiou SH, et al. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol. 2008;10(3):295-305.
67.Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature. 1996 4;379(6560):88-91.
68.Garg AD, Maes H, van Vliet AR, Agostinis P. Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress. Mol Cell Oncol. 2014;2(1):e975089.
69.Wang YC, Dong J, Nie J, et al. Amelioration of bleomycin-induced pulmonary fibrosis by chlorogenic acid through endoplasmic reticulum stress inhibition. Apoptosis. 2017;22(9):1147-1156.
70.Marciniak SJ. Endoplasmic reticulum stress in lung disease. Eur Respir Rev. 2017;26(144).
71.Teng YC, Neo JC, Wu JC, Chen YF, Kao CH, Tsai TF. Expression of a hepatitis B virus pre-S2 deletion mutant in the liver results in hepatomegaly and hepatocellular carcinoma in mice. J Pathol. 2017;241(4):463-474.
72.Zhong JT, Yu J, Wang HJ, et al. Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway. Tumour Biol. 2017;39(5):1010428317697562.
73.Sreenath TL, Macalindong SS, Mikhalkevich N, et al. ETS Related Gene mediated Androgen Receptor Aggregation and Endoplasmic Reticulum Stress in Prostate Cancer Development. Sci Rep. 2017;7(1):1109.
74.Miura K, Titani K, Kurosawa Y, Kanai Y. Molecular cloning of nucleobindin, a novel DNA-binding protein that contains both a signal peptide and a leucine zipper structure. Biochem Biophys Res Commun. 1992;187(1):375-80.
75.Gonzalez R, Mohan H, Unniappan S. Nucleobindins: bioactive precursor proteins encoding putative endocrine factors? Gen. Comp. Endocrinol. 2012;176(3):341-346.
76.Xu H, Li W, Qi K, Zhou J, Gu M, Wang Z. A novel function of NUCB2 in promoting the development and invasion of renal cell carcinoma. Oncol Lett. 2018;15(2):2425-2430.
77.Wei Y, Li J, Wang H, Wang G. NUCB2/nesfatin-1: Expression and functions in the regulation of emotion and stress. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:221-227.
78.Oh-I S, Shimizu H, Satoh T, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006;443(7112):709-12.
79.Dore R, Levata L, Lehnert H, Schulz C. Nesfatin-1: functions and physiology of a novel regulatory peptide. J Endocrinol. 2017;232(1):R45-R65.
80.Hogeweg P. The roots of bioinformatics in theoretical biology. PLoS Comput Biol. 2011;7(3):e1002021.
81.Collins F1, Galas D. A new five-year plan for the U.S. Human Genome Project. Science. 1993;262(5130):43-6.
82.Sayers EW, Beck J, Brister JR, et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 2020;48(D1):D9-D16.
83.Attwood TK, Bongcam-Rudloff E, Brazas ME, et al. Correction: GOBLET: The Global Organisation for Bioinformatics Learning, Education and Training. PLoS Comput Biol. 2015;11(5):e1004281.
84.Ison J, Kalas M, Jonassen I, et al. EDAM: an ontology of bioinformatics operations, types of data and identifiers, topics and formats. Bioinformatics. 2013;29(10):1325-32.
85.Marum L. Cancer Cell Line Encyclopedia launched by Novartis and Broad Institute. Future Med Chem. 2012;4(8):947.
86.Barretina J, Caponigro G, Stransky N, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483(7391):603-7.
87.Szklarczyk D, Franceschini A, Kuhn M, et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2011;39(Database issue):D561-8.
88.Pontén F, Schwenk JM, Asplund A, Edqvist PH. The Human Protein Atlas as a proteomic resource for biomarker discovery. J Intern Med. 2011;270(5):428-46.
89.Persson A, Hober S, Uhlén M. A human protein atlas based on antibody proteomics. Curr Opin Mol Ther. 2006;8(3):185-90.
90.Wang XQ, Zheng Y, Fang PF, Song XB. Nesfatin-1 is a potential diagnostic biomarker for gastric cancer. Oncol Lett. 2020;19(2):1577-1583.
91.Liu GM, Xu ZQ, Ma HM. Nesfatin-1/Nucleobindin-2 Is a Potent Prognostic Marker and Enhances Cell Proliferation, Migration, and Invasion in Bladder Cancer. Dis Markers. 2018;2018:4272064.
92.Kan JY, Yen MC, Wang JY, et al. Nesfatin-1/Nucleobindin-2 enhances cell migration, invasion, and epithelial-mesenchymal transition via LKB1/AMPK/TORC1/ZEB1 pathways in colon cancer. Oncotarget. 2016;7(21):31336-49.
93.Sun S, Yang H. Tissue-Specific Localization NUCB2/nesfatin-1 in the Liver and Heart of Mouse Fetus. Dev Reprod. 2018;22(4):331-339.
94. Zhao J, Yun X, Ruan X, et al. High expression of NUCB2 promotes papillary thyroid cancer cells proliferation and invasion. Onco Targets Ther. 2019;12:1309-1318.
95.Hofmann T, Weibert E, Ahnis A, et al. Alterations of circulating NUCB2/nesfatin-1 during short term therapeutic improvement of anxiety in obese inpatients. Psychoneuroendocrinology. 2017;79:107-115.
96.Lee WS, Yoo WH, Chae HJ. ER Stress and Autophagy. Curr Mol Med. 2015;15(8):735-745.
97.Rashid HO, Yadav RK, Kim HR, Chae HJ. ER stress: Autophagy induction, inhibition and selection. Autophagy. 2015;11(11):1956-1977.
98.Kapoor N, Gupta R, Menon ST, Folta-Stogniew E, Raleigh DP, Sakmar TP. Nucleobindin 1 is a calcium-regulated guanine nucleotide dissociation inhibitor of G{alpha}i1. J Biol Chem. 2010;285(41):31647-31660.
99.Wang C, Wang Y, Hu W. Association of the polymorphism in NUCB2 gene and the risk of type 2 diabetes. Diabetol Metab Syndr. 2017;9:39.

電子全文 電子全文(網際網路公開日期:20250827)
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top