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Structure study and function analysis of tumor related genes in human malignancies

Research summary

In 1978, our laboratory launched the cytogenetic research in human solid tumors. From the initial cytogenetic analysis in solid tumors to the molecular-DNA level research in the 1990s, our laboratory has been dedicated in the gene structure and function research in human malignant tumors. In 2001, the study of “Cytogenetic Research in Solid Tumor” was awarded with the second prize of National Scientific and Technological Progress Award.

Research fields

1. Identification, localization and cloning of tumor related genes in human solid tumor.

2. Biological function analysis of tumor related genes in human solid tumor.

3. Molecular and regulatory mechanism research of tumor related genes in human solid tumor.

4. Signal transduction pathway study of tumor related genes in human solid tumor.

Research achievements

Established bank for human solid tumors

In collaboration with the First, Second and  Third Affiliated Hospitals of Harbin Medical University, we have collected the blood and tissue samples of patients with common solid tumors in north China. So far, we have established a tumor genetic resource library of north China, including but not limited to stomach cancer, colorectal cancer, lung cancer and ovarian cancer.

Publications (*correspondence author)


1. Pang B, Wu N, Guan R, Pang L, Li X, Li S, Tang L, Guo Y, Chen J, Sun D, Sun H, Dai J, Bai J, Ji G, Liu P, Liu A, Wang Q, Xiao S, Fu S*, Jin Y*.(2017)Overexpression of RCC2 Enhances Cell Motility and Promotes Tumor Metastasis in Lung Adenocarcinoma by Inducing Epithelial-Mesenchymal Transition. Clin Cancer Res. 15;23(18):5598-5610.

2. Li Y, Sun H, Zhang C, Liu J, Zhang H, Fan F, Everley RA, Ning X, Sun Y, Hu J, Liu J, Zhang J, Ye W, Qiu X, Dai S, Liu B, Xu H, Fu S, Gygi SP, Zhou C*. (2017)Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity pro- teomics. Oncogene. 2017 Dec 14; 36(50):6839-6849.

3. You J, Liu J, Bao Y, Wang L, Yu Y, Wang L, Wu D, Liu C, Wang N, Wang F, Wang F, Xu L, Tian X, Liang H, Gao Y, Guan R, Bai J, Meng X, Sun W, Guan XY, Zhang C*, Fu S*, Jin Y*.(2017)SEI1 induces genomic instability by inhibiting DNA damage response in ovarian cancer. Cancer Lett. 28;385:271-279.

4. Zhu J, Zhang F, Du M, Zhang P, Fu S, Wang L*.(2017)Molecular characterization of cell-free eccD- NAs in human plasma.Sci Rep. 8;7(1):10968.

5. Wang Y, Wu N, Pang B, Tong D, Sun D, Sun H, Zhang C, Sun W, Meng X, Bai J, Chen F, Geng J, Fu S*, Jin Y*. (2017)TRIB1 promotes colorectal cancer cell migration and invasion through activation MMP- 2 via FAK/Src and ERK pathways. Oncotarget. 8(29):47931-47942.

6. Wang Y, Wu N, Sun D, Sun H, Tong D, Liu D, Pang B, Li S, Wei J, Dai J, Liu Y, Bai J, Geng J, Fu S*, Jin Y*. (2017)NUBPL, a novel metastasis-related gene, promotes colorectal carcinoma cell motility by inducing epithelial-mesenchymal transition. Cancer Sci. 108(6):1169-1176.

7. Liu D, Wu N, Sun H, Dong M, Guo T, Chi P, Li G, Sun D, Jin Y*.(2017)ABCG2 and NCF4 polymor- phisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R- CHOP.Oncotarget. 8(35):58292-58303.

8. Sun H, Zhang X, Sun D, Jia X, Xu L, Qiao Y, Jin Y*. (2017)COX-2 expression in ovarian cancer: an updated meta-analysis. Oncotarget. 8(50):88152-88162.

9. Sun W, Rojas Y, Wang H, Yu Y, Wang Y, Chen Z, Rajapakshe K, Xu X, Huang W, Agarwal S, Patel R, Woodfield S, Zhao Y, Jin J, Zhang H, Major A, Hicks MJ, Shohet J, Vasudevan S, Coarfa C, Yang J, Nuchtern J*. (2017)EWS-FLI1 and RNA helicase A interaction inhibitor YK-4-279 inhibits growth of neuroblastoma.Oncotarget. 208(55): 94780-94792.

10. Wang B, Qi X, Li D, Feng M, Meng X, Fu S. (2016)Expression of pY397 FAK promotes the development of non-small cell lung cancer. Oncol Lett. 11(2):979-983.

11. ZEHUA BIAN, YANG YU, CHAO QUAN, RONGWEI GUAN, YAN JIN, JIE WU, LIDAN XU, FENG CHEN, JING BAI, WENJING SUN,SONGBIN FU*.(2015)RPL13A as a reference gene for normalizing mRNA transcription of ovarian cancer cells with paclitaxel and 10-hydroxycamptothecin treatments. Mol Med Rep. 11(4):3188-94.

12. Huiyuan Zhang, Jun Dou, Yang Yu, Yanling Zhao, Yihui Fan, Jin Cheng, Xin Xu, Wei Liu, Shan Guan, Zhenghu Chen, Yan shi, Roma Patel, Sanjeev A,  Vasudevan, Peter E. Zage, Hong Zhang, Jed G. Nuchtern, Eugene S. Kim, Songbin Fu*, Jianhua Yang*.(2015) mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling. Apoptosis. 20(1):50-62.

13. Xu H, Sun H, Zhang H, Liu J, Fan F, Li Y, Ning X, Sun Y, Dai S, Liu B, Gao M, Fu S, Zhou C*.(2015)An ShRNA Based Genetic Screen Identified Sesn2 as a Potential Tumor Suppressor in Lung Cancer via Suppression of Akt-mTOR-p70S6K Signaling.PLoS One. 11;10(5):e0124033

14. Xu H, Dephoure N, Sun H, Zhang H, Fan F, Liu J, Ning X, Dai S, Liu B, Gao M, Fu S, Gygi SP*, Zhou C*. (2015) Proteomic Profiling of Paclitaxel Treated Cells Identifies a Novel Mechanism of Drug Resistance Mediated by PDCD4.J Proteome Res. 14(6):2480-91.

15. Nan Wu, Jia Wei, Yuhui Wang, Jinyan Yan, Ying Qin, Dandan Tong, Bo Pang, Donglin Sun, Haiming Sun, Yang Yu, Wenjing Sun, Xiangning Meng, Chunyu Zhang, Jing Bai, Feng Chen, Jingshu Geng, Ki-Young Lee, Songbin Fu*, Yan Jin*. (2015) Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition. Plos One. 10(11)e0143659

16. Bian Z, Yu Y, Yang T, Quan C, Sun W, Fu S*.(2014) Effect of tumor suppressor gene cyclin-dependent kinase inhibitor 2A wild-type and A148T mutant on the cell cycle of human ovarian cancer cells.OncolLett.7(4):1229-1232.

17. Jie WuSol KimMan Sup KwakJang Bin JeongHyun Jin MinHo-Geun YoonJin-Hyun Ahn Jeon-Soo Shin*.2014High Mobility Group Nucleosomal Binding Domain 2 (HMGN2) SUMOylation by the SUMO E3 Ligase PIAS1 Decreases the Binding Affinity to Nucleosome Core Particles. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 28929:20000–20011

18. Zhao Y, Liang L, Fan Y, Sun S, An L, Shi Z, Cheng J, Jia W, Sun W, Mori-Akiyama Y, Zhang H, Fu S, Yang J*. (2012) PPM1B negatively regulates antiviral response via dephosphorylating TBK1. Cell Signal. 24(11):2197-204. PMID:22750291

19. Sun W, Guo C, Meng X, Yu Y, Jin Y, Tong D, Geng J, Huang Q, Qi J, liu A, Guan R, Xu L, Sun D, Ji W, Liu P, Liu F, Sun H, Ji G, Fu S, Bai J*. (2012) Differential expression of PAI-RBP1, Clorf142 and COTL1 in NSCLC cell lines with different tumor metastatic potential. J Investig Med. 60(4):689-94. PMID:22373659

20. Bai J, Guo C, Sun W, Li M, Meng X, Yu Y, Jin Y, Tong D, Geng J, Huang Q, Qi J, Fu S*. (2012) DJ-1 may contribute to metastasis of non-small cell lung cancer. Mol Biol Rep. 39(3):2697-703. PMID: 21670963

21. Lee KY, Liu L, Jin Y, Fu SB, Rosales JL*. (2012) Cdk5 mediates vimentin Ser56 phosphorylation during GTP-induced secretion by neutrophils. J Cell Physiol. 227(2):739-50. PMID: 21465480

22. Meng X, Wang G, Liu P, Hou J, Jin Y, Yu Y, Bai J, Chen F, Sun W, Fu S*. (2011) ATP-binding cassette B1 gene polymorphisms, mRNA expression and chemosensitivity to paclitaxel in non-small cell lung cancer cells. Respirology. 16(8):1228-34. PMID: 21883677

23. Jung J, Lee MK, Jin Y, Fu SB, Rosales JL, Lee KY*. (2011) Clues for c-Yes involvement in the cell cycle and cytokinesis. Cell Cycle. 10(9):1502-3. PMID: 21566460

24. Yu J, Liu P, Cui X, Sui Y, Ji G, Guan R, Sun D, Ji W, Liu F, Liu A, Zhao Y, Yu Y, Jin Y, Bai J, Geng J, Xue Y, Qi J, Lee KY, Fu S*. (2011) Identification of novel subregions of LOH in gastric cancer and analysis of the HIC1 and TOB1 tumor suppressor genes in these subregions. Mol Cells. 32(1):47-55. PMID: 21533545

25. Kim T, Park JS, Lee P, Jin Y, Fu SB, Rosales JL, Lee KY*. (2011) Novel alternatively spliced variant form of human CDK5RAP2. Cell Cycle. 10(6). PMID: 21346412

26. Fan YH, Yu Y, Mao RF, Tan XJ, Xu GF, Zhang H, Lu XB, Fu SB, Yang J*. (2011) USP4 targets TAK1 to downregulate TNFα-induced NF-κB activation. Cell Death Differ. 18(10):1547-60. PMID: 21331078

27. Shi Z, Cai Z, Sanchez A, Zhang T, Wen S, Wang J, Yang J, Fu S*, Zhang D*. (2011) A novel Toll-like receptor that recognizes vesicular stomatitis virus. J Biol Chem. 286(6):4517-24. PMID: 21131352

28. Mao R, Fan Y, Mou Y, Zhang H, Fu S, Yang J*. (2011) TAK1 lysine 158 is required for TGF-β-induced TRAF6-mediated Smad-independent IKK/NF-κB and JNK/AP-1 activation. Cell Signal. 23(1):222-7. PMID: 20837137

29. Wang QS, Li M, Zhang LY*, Jin Y, Tong DD, Yu Y, Bai J, Huang Q, Liu FL, Liu A, Lee KY, Fu SB*. (2010) Down-regulation of ING4 is associated with initiation and progression of lung cancer. Histopathology. 57(2):271-81. PMID: 20716169

30. Zhang W, Zhu J, Bai J, Jiang H, Liu F, Liu A, Liu P, Ji G, Guan R, Sun D, Ji W, Yu Y, Jin Y, Meng X, Fu S*. (2010) Comparison of the inhibitory effects of three transcriptional variants of CDKN2A in human lung cancer cell line A549. J Exp Clin Cancer Res. 29:74. PMID: 20565749

31. Sun W, Wang H, Zhao X, Yu Y, Fan Y, Wang H, Wang X, Lu X, Zhang G, Fu S*, Yang J*. (2010) Protein phosphatase 2A acts as a mitogen-activated protein kinase kinase kinase 3 (MEKK3) phosphatase to inhibit lysophosphatidic acid-induced IkappaB kinase beta/nuclear factor-kappaB activation. J Biol Chem. 285(28):21341-8. PMID: 20448038

32. Sun W, Ge N, Yu Y, Burlingame S, Li X, Zhang M, Ye S, Fu S, Yang J*. (2010) Phosphorylation of Thr-516 and Ser-520 in the kinase activation loop of MEKK3 is required for lysophosphatidic acid-mediated optimal IkappaB kinase beta (IKKbeta)/nuclear factor-kappaB (NF-kappaB) activation. J Biol Chem. 285(11):7911-8. PMID: 20068038

33. Fan Y, Yu Y, Shi Y, Sun W, Xie M, Ge N, Mao R, Chang A, Xu G, Schneider MD, Zhang H, Fu S, Qin J, Yang J*. (2010) Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1 activation. J Biol Chem. 285(8):5347-60. PMID: 20038579

34. Sun W, Tan X, Shi Y, Xu G, Mao R, Gu X, Fan Y, Yu Y, Burlingame S, Zhang H, Rednam SP, Lu X, Zhang T, Fu S, Cao G, Qin J, Yang J*. (2010) USP11 negatively regulates TNFalpha-induced NF-kappaB activation by targeting on IkappaBalpha. Cell Signal. 22(3):386-94. PMID: 19874889

35. Liu F, Yu Y, Jin Y, Fu S*. (2010) TSG101, identified by screening a cancer cDNA library and soft agar assay, promotes cell proliferation in human lung cancer. Mol Biol Rep. 37(6):2829-38. PMID: 19787439

36. Li C, Shi Z, Zhang L, Huang Y, Liu A, Jin Y, Yu Y, Bai J, Chen D, Gendron C, Liu X, Fu S*. (2010) Dynamic changes of territories 17 and 18 during EBV-infection of human lymphocytes. Mol Biol Rep. 37(5):2347-54. PMID: 19685159

37. Fan Y, Mao R, Zhao Y, Yu Y, Sun W, Song P, Shi Z, Zhang D, Yvon E, Zhang H, Fu S, Yang J*. (2009) Tumor necrosis factor-alpha induces RelA degradation via ubiquitination at lysine 195 to prevent excessive nuclear factor-kappaB activation. J Biol Chem. 284(43):29290-7. PMID: 19706600

38. Zhang C, Fu L, Fu J, Hu L, Yang H, Rong TH, Li Y, Liu H, Fu SB, Zeng YX, Guan XY*. (2009) Fibroblast growth factor receptor 2-positive fibroblasts provide a suitable microenvironment for tumor development and progression in esophageal carcinoma. Clin Cancer Res. 15(12):4017-27. PMID: 19509166

39. Shi Z, Cai Z, Wen S, Chen C, Gendron C, Sanchez A, Patterson K, Fu S, Yang J, Wildman D, Finnell RH, Zhang D*. (2009) Transcriptional regulation of the novel Toll-like receptor Tlr13. J Biol Chem. 284(31):20540-7. PMID: 19487701

40. Li M, Jin Y, Sun WJ, Yu Y, Bai J, Tong DD, Qi JP, Du JR, Geng JS, Huang Q, Huang XY, Huang Y, Han FF, Meng XN, Rosales JL, Lee KY, Fu SB*. (2009) Reduced expression and novel splice variants of ING4 in human gastric adenocarcinoma. J Pathol. 219(1):87-95. PMID: 19479822

41. Meng XN, Jin Y, Yu Y, Bai J, Liu GY, Zhu J, Zhao YZ, Wang Z, Chen F, Lee KY, Fu SB*. (2009) Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration and invasion. Br J Cancer. 101(2):327-34. PMID: 19568240

42. Sun W, Li H, Yu Y, Fan Y, Grabiner BC, Mao R, Ge N, Zhang H, Fu S, Lin X, Yang J*. (2009) MEKK3 is required for lysophosphatidic acid-induced NF-kappaB activation. Cell Signal. 21(10):1488-94. PMID: 19465115

43. Sun W, Yu Y, Dotti G, Shen T, Tan X, Savoldo B, Pass AK, Chu M, Zhang D, Lu X, Fu S, Lin X, Yang J*. (2009) PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation. Cell Signal. 21(1):95-102. PMID: 18930133

44. Tong DD, Jiang Y, Li M, Kong D, Meng XN, Zhao YZ, Jin Y, Bai J, Fu SB, Geng JS*. (2009) RUNX3 inhibits cell proliferation and induces apoptosis by TGF-beta-dependent and -independent mechanisms in human colon carcinoma cells. Pathobiology. 76(4):163-9. PMID: 19571605

45. Wang X, Sun W, Bai J, Ma L, Yu Y, Geng J, Qi J, Shi Z, Fu S*. (2009) Growth inhibition induced by transforming growth factor-beta1 in human oral squamous cell carcinoma. Mol Biol Rep. 36(5):861-9. PMID: 18418730

46. Yu J, Zhou H, Jin Y, Bai J, Yu Y, Geng J, Qi J, Fu S*. (2008) Three distinct regions of allelic deletion on chromosome 17 involved in sporadic gastric cancer. Hepatogastroenterology. 55(85):1487-91. PMID: 18795719

47. Yu Y, Ge N, Xie M, Sun W, Burlingame S, Pass AK, Nuchtern JG, Zhang D, Fu S, Schneider MD, Fan J, Yang J*. (2008) Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop is required for interleukin (IL)-1-mediated optimal NFkappaB and AP-1 activation as well as IL-6 gene expression. J Biol Chem. 283(36):24497-505. PMID: 18617512

48. Liu G, Meng X, Jin Y, Bai J, Zhao Y, Cui X, Chen F, Fu S*. (2008) Inhibitory role of focal adhesion kinase on anoikis in the lung cancer cell A549. Cell Biol Int. 32(6):663-70. PMID: 18343694

49. Yu JC, Zhou H, Bai J, Yu Y, Geng JS, Qi JP, Fu SB*. (2008) Human gastric adenocarcinoma allelotype on chromosomes 17 and 18. J Int Med Res. 36(2):279-88. PMID: 18380938

50. Li X, Yue ZC, Zhang YY, Bai J, Meng XN, Geng JS, Fu SB*. (2008) Elevated serum level and gene polymorphisms of TGF-beta1 in gastric cancer. J Clin Lab Anal. 22(3):164-71. PMID: 18484655

51. Huang Y, Jin Y, Yan CH, Yu Y, Bai J, Chen F, Zhao YZ, Fu SB*. (2008) Involvement of Annexin A2 in p53 induced apoptosis in lung cancer. Mol Cell Biochem. 309(1-2):117-23. PMID: 18008140

52. Cui X, Gao L, Jin Y, Zhang Y, Bai J, Feng G, Gao W, Liu P, He L, Fu S*. (2007) The E233del mutation in BFSP2 causes a progressive autosomal dominant congenital cataract in a Chinese family. Mol Vis. 13:2023-9. PMID: 17982427

53. Huang X, Shi Z, Wang W, Bai J, Chen Z, Xu J, Zhang D, Fu S*. (2007) Identification and characterization of a novel protein ISOC2 that interacts with p16INK4a. Biochem Biophys Res Commun. 361(2):287-93. PMID: 17658461

54. Liu F, Li Y, Yu Y, Fu S, Li P*. (2007) Cloning of novel tumor metastasis-related genes from the highly metastatic human lung adenocarcinoma cell line Anip973. J Genet Genomics. 34(3):189-95. PMID: 17498616

55. Zhang CY, Feng YX, Yu Y, Sun WJ, Bai J, Chen F, Fu SB*. (2006) The molecular mechanism of resistance to methotrexate in mouse methotrexate-resistant cells by cancer drug resistance and metabolism SuperArray. Basic Clin Pharmacol Toxicol. 99(2):141-5. PMID: 16918715

56. Yan J, Yun H, Yang Y, Jing B, Feng C, Song-bin F*. (2006) Upregulation of BNIP3 promotes apoptosis of lung cancer cells that were induced by p53. Biochem Biophys Res Commun. 346(2):501-7. PMID: 16765911

57. Ma LL, Sun WJ, Wang Zh, Zh GY, Li P, Fu SB*. (2006) Effects of silencing of mutant p53 gene in human lung adenocarcinoma cell line Anip973. J Exp Clin Cancer Res. 25(4):585-92. PMID: 17310850

58. Shi ZC, Yu Y, Li Y, Fu SB*. (2005) The effect of RAB5A gene on rearrangement of microfilaments in human lung adenocarcinoma cells. Yi Chuan Xue Bao. 32(12):1227-34. PMID: 16459650

59. Gao L, Qin W, Cui H, Feng G, Liu P, Gao W, Ma L, Li P, He L, Fu S*. (2005) A novel locus of coralliform cataract mapped to chromosome 2p24-pter. J Hum Genet. 50(6):305-10. PMID: 15933805

60. Li X, Zhang YY, Wang Q, Fu SB*. (2005) Association between endogenous gene expression and growth regulation induced by TGF-beta1 in human gastric cancer cells. World J Gastroenterol. 11(1):61-8. PMID: 15609398

61. Yu JC, Sun KL, Liu B, Fu SB*. (2004) Allelotyping for loss of heterozygosity on chromosome 18 in gastric cancer. World J Gastroenterol. 10(13):1964-6. PMID: 15222047

62. Wang Q, Tsao SW, Fu S, Xue W, Meng X, Feng H, Wong YC, Wang X*. (2004) Overexpression of Id-1 in gastric adenocarcinoma: implication for a novel diagnostic marker. Anticancer Res. 24(2B):881-6. PMID: 15161041

63. Wang Q, Wang B, Guan X, Gao H, Cheng H, Zhang Q, Huang C, Li P, Fu S*. (2003) Analysis of comparative genomic hybridization and loss of heterozygosity in 43 primary gastric carcinomas. Chin Med J (Engl). 116(4):517-23. PMID: 12875714

64. Guan XY, Fu SB, Xia JC, Fang Y, Sham JS, Du BD, Zhou H, Lu S, Wang BQ, Lin YZ, Liang Q, Li XM, Du B, Ning XM, Du JR, Li P, (2000) Trent JM. Recurrent chromosome changes in 62 primary gastric carcinomas detected by comparative genomic hybridization. Cancer Genet Cytogenet. 123(1):27-34. PMID: 11120330

65. Xia JC, Lu S, Geng JS, Fu SB, Li P, Liu QZ. (1998) Direct chromosome analysis of ten primary gastric cancers. Cancer Genet Cytogenet. 102(1):88-90. PMID: 9530349

66. Fu SB*, Li P. (1997) Cytogenetic study of twenty-three primary squamous cell carcinomas of the lung. Cancer Genet Cytogenet. 99(1):54-8. PMID: 9352796

67. Fu SB*, Wang BQ, Li P. (1997) Frequent somatic mutation of the MTS1/CDK4I gene in human non-small cell lung carcinomas. Chin Med Sci J. 12(4):251

68. Fu SB*, Li P, Feng XL, Liu CX, Liu QZ. (1994) The origin of isochromosomes and their significance in tumorigenesis of human lung cancer. Cancer Genet Cytogenet. 74(2):120-2. PMID: 8019955

69. Lu YJ, Xiao S, Yan YS, Fu SB, Liu QZ, Li P*. (1993) Direct chromosome analysis of 50 primary breast carcinomas. Cancer Genet Cytogenet. 69(2):91-9. PMID: 8402564


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