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论坛嘉宾介绍:陈扬超教授
来源: | 作者:geneseed | 发布时间: 2019-07-10 | 285 次浏览 | 分享到:
陈扬超  博士/教授(香港中文大学生物医学院)

报告主题:circFOXK2 promotes tumor growth and metastasis of pancreatic ductal adenocarcinoma via complexing with YBX1 and hnRNPK 




嘉宾简介:

香港中文大学生物医学院博士生导师、终身教职;兼任香港中文大学深圳研究院研究员。从事胰腺癌及肝癌的分子生物学﹑基因表达调控﹑非编码RNA及新药物治疗靶点的研究。以课题负责人身份获得7项香港研究资助局一般研究基金、3项香港食品与卫生局健康与医学研究基金、2项香港创新与技术基金、1项美国比尔梅林达盖茨基金会探索大挑战基金、3项企业资助项目、3项国家自然科学基金及2项深圳市基础研究项目。以通讯或第一作者在Gastroenterology, Hepatology, Cancer Research等国际期刊发表论文40余篇。以合作作者在Nature Communication, J Natl Cancer InstHepatology, Gut等期刊发表论文40余篇。任欧洲科学基金、意大利卫生部基金、波兰国家科学基金、澳门科学技术发展基金、澳门大学基金、中国国家自然科学基金及深圳市科创委基金的课题评审人,任World J GastroenterologyAm J Mol Biol等期刊编委,任Cancer ResearchOncogene 等国际期刊的特约审稿人。

 

代表性成果介绍:

Cancer Research肝细胞癌中抑癌基因样功能的非编码RNA分析

201924Cancer Research杂志在线发表了香港中文大学医学院超教授为通讯作者的研究论文,报道在肝细胞癌中筛选受EZH2调控抑制表达的非编码RNA,其中TCAM1P-004  RP11-598D14.1在肝细胞癌细胞系中显著低表达,本文主要针对这两个lncRNA进行了功能和机制研究。

DZnepEZH2的抑制剂,本文作者从经过DZnep处理后能够恢复表达的分子中表达差异显著的非编码RNA中富集到10个非编码RNA分子,其中包括TCAM1P-004  RP11-598D14.1。功能验证表明在HCC 细胞系中干扰两种lncRNA均可明显促进细胞增殖。RNA pull-down实验鉴定到两种lncRNA相互作用的蛋白,TCAM1P-004IGF2BP1 hHIST1H1C相互作用,RP11-598D14.1IGF2BP1STAU1相互作用。(参考文献[1]


HCCTCAM1P-004  RP11-598D14.1作用机制(参考文献[1]


Cancer Research调控miR34a表达的小分子化合物

2014912 Cancer Research杂志在线发表了香港中文大学医学院超教授为通讯作者的研究论文,报道基于高通量筛选分析筛选得到一种可以显著提高mR34a表达的小分子化合物Rubone

本文设计的高通量筛选体系概括而言,是将miR34a的靶向识别位点设计表达在荧光素酶基因的下游,两者一起转录形成一条成熟的mRNA产物(构建一种3’UTRmiR34a靶向序列的mRNA),如果药物处理后能促进miR34a的表达,一定会造成报告基因的表达降低,可以通过测定荧光素酶的发光效率实现定量分析。将稳定表达该报告系统的细胞构建稳定细胞系,然后基于孔板筛选化合物库,定量分析化合物对荧光素酶信号的影响,可以筛选获得能调控miR34a的化合物。基于这种高通量筛选体系,作者得到了Rubone这个化合物。浓度梯度实验证明Rubone可显著上调miR34a的表达,降低荧光素酶报告基因的信号。Rubone可以在p53野生型或突变的细胞中诱导miR34a表达,但在p53缺失的细胞中作用不明显。Rubone对非肿瘤的细胞毒性很小,预示着该化合物具有潜在的作为药物的价值。(参考文献[10]


高通量筛选调控miR34a表达的化合物(参考文献[10]

 

Gastroenterology胰腺导管癌中EZH2通过诱导形成异染色质沉默miR-218的表达

          20135 Gastroenterology杂志发表了香港中文大学医学院超教授为通讯作者的研究论文,报道发现胰腺导管癌中EZH2通过介导H3K27me3修饰,在miR-128的启动子区域诱导形成异染色质,导致miR-128的表达沉默。(参考文献[18]


EZH2通过诱导形成异染色质沉默miR-218的表达(参考文献[18]



代表性研究成果列表


1. Xu F, Li CH, Wong CH, Chen GG, Lai PBS, Shao S, Chan SL, Chen Y*. Genome-Wide Screening and Functional Analysis Identifies Tumor Suppressor Long Noncoding RNAs Epigenetically Silenced in Hepatocellular Carcinoma. Cancer Res. 2019 Apr 1;79(7):1305-1317. doi: 10.1158/0008-5472.CAN-18-1659

2.WongCH,ChenYC.Clinical significance of exosomes as potential biomarkers in cancer. World J Clin Cases. 2019 Jan 26;7(2):171-190. doi: 10.12998/wjcc.v7.i2.171

3. Li CH, Tang SC, Wong CH, Wang Y, Jiang JD, Chen Y*. Berberine induces miR-373 expression in hepatocytes to inactivate hepatic steatosis associated AKT-S6 kinase pathway. Eur J Pharmacol. 2018 Apr 15;825:107-118. doi: 10.1016/j.ejphar.2018.02.035

4. Xiao Z, Chen Y*. Identification of Small Molecule Modulators of MicroRNA by Library Screening. Methods Mol Biol. 2017;1517:169-178

5. Li CH, Xiao Z, Tong JH, To KF, Fang X, Cheng AS, Chen Y*. EZH2 coupled with HOTAIR to silence MicroRNA-34a by the induction of heterochromatin formation in human pancreatic ductal adenocarcinoma. Int J Cancer. 2017 Jan 1;140(1):120-129. doi: 10.1002/ijc.30414

6. Li CH, Chen Y*. Diagnostic Potential of lncRNAs in Cancer. EBioMedicine. 2016 May;7:7-8. doi: 10.1016/j.ebiom.2016.05.013

7. Han Li C, Chen Y*. Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy. Curr Genomics. 2015 Oct;16(5):319-26. doi: 10.2174/1389202916666150707155851.

8. Han Li C, Chen Y*. Targeting EZH2 for cancer therapy: progress and perspective. Curr Protein Pept Sci. 2015;16(6):559-70.

9. Xiao Z, Chen Y*. Small molecule targeting miR-34a for cancer therapy. Mol Cell Oncol. 2015 Feb 24;2(1):e977160. doi: 10.4161/23723556.2014.977160

10. Xiao Z, Li CH, Chan SL, Xu F, Feng L, Wang Y, Jiang JD, Sung JJ, Cheng CH, Chen Y*. A small-molecule modulator of the tumor-suppressor miR34a inhibits the growth of hepatocellular carcinoma. Cancer Res. 2014 Nov 1;74(21):6236-47. doi: 10.1158/0008-5472

11. Li CH, Xu F, Chow S, Feng L, Yin D, Ng TB, Chen Y*. Hepatitis B virus X protein promotes hepatocellular carcinoma transformation through interleukin-6 activation of microRNA-21 expression. Eur J Cancer. 2014 Oct;50(15):2560-9. doi: 10.1016/j.ejca.2014.07.008

12.TangSC,ChenYC*. Novel therapeutic targets for pancreatic cancer. World J Gastroenterol. 2014 Aug 21;20(31):10825-44. doi: 10.3748/wjg.v20.i31.10825

13. He CY, Fu J, Ma JY, Feng R, Tan XS, Huang M, Shou JW, Zhao ZX, Li XY, Zhang XF*, Chen Y*, Wang Y*. Biotransformation and in vitro metabolic profile of bioactive extracts from a traditional Miao-nationality herbal medicine, Polygonum capitatum. Molecules. 2014 Jul 16;19(7):10291-308. doi: 10.3390/molecules190710291

14. Ma JY, Zhou X, Fu J, Hu T, Or PM, Feng R, He CY, Chen WJ, Zhang X*, Chen Y*, Wang Y*, Yeung JH. Metabolite profiling analysis of FR429, an ellagitannin purified from Polygonum capitatum, in rat and human liver microsomes, cytosol and rat primary hepatocytes in vitro. Chem Biol Interact. 2014 Sep 5;220:33-40. doi: 10.1016/j.cbi.2014.06.002

15. Xiao Z, Ching Chow S, Han Li C, Chun Tang S, Tsui SK, Lin Z, Chen Y*. Role of microRNA-95 in the anticancer activity of Brucein D in hepatocellular carcinoma. Eur J Pharmacol. 2014 Apr 5;728:141-50. doi: 10.1016/j.ejphar.2014.02.002.

16. Wang Y, Ma J, Chow SC, Li CH, Xiao Z, Feng R, Fu J, Chen Y*. A potential antitumor ellagitannin, davidiin, inhibited hepatocellular tumor growth by targeting EZH2. Tumour Biol. 2014 Jan;35(1):205-12. doi: 10.1007/s13277-013-1025-3

17. Li CH, Chen Y*. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol. 2013 Aug;45(8):1895-910. doi: 10.1016/j.biocel.2013.05.030.

18. Li CH, To KF, Tong JH, Xiao Z, Xia T, Lai PB, Chow SC, Zhu YX, Chan SL, Marquez VE, Chen Y*. Enhancer of Zeste Homolog 2 Silences MicroRNA-218 in Human Pancreatic Ductal Adenocarcinoma Cells by Inducing Formation of Heterochromatin. Gastroenterology. 2013 May;144(5):1086-1097.e9. doi: 10.1053/j.gastro.2013.01.058.

19. Diao S, Zhang JF, Wang H, He ML, Lin MC, Chen Y*, Kung HF*. Proteomic identification of microRNA-122a target proteins in hepatocellular carcinoma. Proteomics. 2010 Oct;10(20):3723-31. doi: 10.1002/pmic.201000050.

20. Chen Y*#, Xie D#, Yin Li W, Man Cheung C, Yao H, Chan CY, Chan CY, Xu FP, Liu YH, Sung JJ, Kung HF*. RNAi targeting EZH2 inhibits tumor growth and liver metastasis of pancreatic cancer in vivo. Cancer Lett. 2010 Nov 1;297(1):109-16. doi: 10.1016/j.canlet.2010.05.003

21. Jiang L#, Chen Y#*, Chan CY, Wang X, Lin L, He ML, Lin MC, Yew DT, Sung JJ, Li JC*, Kung HF. Down-regulation of stathmin is required for TGF-beta inducible early gene 1 induced growth inhibition of pancreatic cancer cells. Cancer Lett. 2009 Feb 8;274(1):101-8. doi: 10.1016/j.canlet.2008.09.017

22. Chen Y#, Cheung YT, Kong LD, Ng TB, Qiao C, Mo SF, Xu HX, Kung HF*. Transcriptional regulation of corticotrophin releasing factor gene by furocoumarins isolated from seeds of Psoralea corylifolia. Life Sci. 2008 May 23;82(21-22):1117-21. doi: 10.1016/j.lfs.2008.03.014

23. Chen Y#, Lin MC, Wang H, Chan CY, Jiang L, Ngai SM, Yu J, He ML, Shaw PC, Yew DT, Sung JJ, Kung HF*. Proteomic analysis of EZH2 downstream target proteins in hepatocellular carcinoma. Proteomics. 2007 Sep;7(17):3097-104.

24. Chen Y#, Lin MC, Yao H, Wang H, Zhang AQ, Yu J, Hui CK, Lau GK, He ML, Sung J, Kung HF*. Lentivirus-mediated RNA interference targeting enhancer of zeste homolog 2 inhibits hepatocellular carcinoma growth through down-regulation of stathmin. Hepatology. 2007 Jul;46(1):200-8

25. Chen Y#, Stamatoyannopoulos G, Song CZ*. Down-regulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro. Cancer Res. 2003 Aug 15;63(16):4801-4.