Research Progress of a Novel Pro-apoptosis Gene PNAS-4 in Gene Therapy and Its Molecular Mechanism Hypotheses_Journal of Biomedical Engineering

Authors：

ZHOUBin ,  LIYuan

Laboratory of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

LIYuan, Email: liyuanletters@163.com

Keywords：

PNAS-4; PPPDE1; apoptosis; gene therapy; molecular mechanisms

DOI：

10.7507/1001-5515.20150244

Video：

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Abstract Full text Figures/Tables Video References Cited by

PNAS-4 is a novel pro-apoptosis gene identified latetly. In recent years, there has been a large number of research reports on the basic studies about PNAS-4 in cancer gene therapy and gene therapy of PNAS-4 alone or combined with chemotherapy or radiotherapy manifested a good application prospect, but its molecular mechanisms to promote apoptosis is not clear yet. In this paper, recent research about PNAS-4 in cancer gene therapy is briefly reviewed, and recent hypotheses on its molecular mechanisms to promote apoptosis are especially elucidated. Based on its newly identified characteristics of structural domain, we made a point that PNAS-4 might regulate functions of some target protein related to apoptosis by deSumoylation as a new deSumoylating isopeptidase, and consequently promote apoptosis.

Citation： ZHOUBin, LIYuan. Research Progress of a Novel Pro-apoptosis Gene PNAS-4 in Gene Therapy and Its Molecular Mechanism Hypotheses. Journal of Biomedical Engineering, 2015, 32(6): 1380-1384. doi: 10.7507/1001-5515.20150244 Copy

1.	董少婷, 杨红丽, 王爽.细胞凋亡在正常和肿瘤组织微环境中的作用[J].国际肿瘤学杂志, 2013, 40(2):92-95.
2.	王贲士, 陈德喜, 郭洪亮.自噬与肿瘤的研究现状[J].中华肿瘤防治杂志, 2014, 21(8):637-640.
3.	李玲, 徐小洁, 叶棋浓.细胞自噬与肿瘤[J].中国生物化学与分子生物学报, 2013, 29(11):995-1001.
4.	武晓燕, 侯玲玲, 晏琼, 等.凋亡素诱导细胞凋亡的机制及其在肿瘤治疗中的应用[J].生理科学进展, 2014, 45(1):45-48.
5.	聂雪坤, 张舒晟, 史道华.调控肿瘤细胞自噬相关分子的研究进展[J].国际肿瘤学杂志, 2013, 40(11):803-806.
6.	丁坚, 蔡军.P53、XIAP与细胞凋亡的关系及其靶向的细胞凋亡在肿瘤治疗中的研究进展[J].实用临床医学, 2013, 14(1):127-130.
7.	王剑龙, 郭刚文, 孙剑锋, 等.促凋亡基因PUMA的研究进展及其与肿瘤的关系[J].中国医药指南, 2013, 11(3):50-52.
8.	YAO Shaohua, XIE Lifang, QIAN Meilin, et al. Pnas4 is a novel regulator for convergence and extension during vertebrate gastrulation[J]. FEBS Lett, 2008, 582(15):2325-2332.
9.	YAN Fei, RUAN Xuzhi, YANG Hanshuo, et al. Identification, characterization, and effects of Xenopus laevis PNAS-4 gene on embryonic development[J]. J Biomed Biotechnol, 2010, 2010:Article ID 134764.
10.	张木子荷, 武鑫, 张丽娟, 等.经修饰的聚阳离子载体在基因治疗中的应用进展[J].药学服务与研究, 2013, 13(1):25-29.
11.	梁迎春, 程龙, 叶棋浓.肿瘤基因治疗的研究进展[J].生物技术通讯, 2012, 23(3):436-439, 460.
12.	王飞, 赵海平.胰腺癌的基因治疗进展[J].中国疗养医学, 2012, 21(5):413-416.
13.	赵嵘, 张锡朋.结直肠肿瘤生物治疗的研究进展[J].继续医学教育, 2014, 28(6):51-54.
14.	王文涛, 秦建军.基因修饰的间充质干细胞在肺部肿瘤治疗中的前景与障碍[J].医药论坛杂志, 2014, 35(3):141-143.
15.	钟林, 李强, 陈飞, 等.结直肠癌基因治疗研究进展[J].岭南现代临床外科, 2014, 14(2):207-210.
16.	宋向明, 赵瑜, 田长富.肿瘤基因治疗的病毒载体研究进展[J].医学综述, 2014, 20(6):1006-1009.
17.	莱智勇, 徐钧.肝癌的基因治疗[J].中国药物与临床, 2014, 14(3):327-330.
18.	安娜, 王忠彦.基因治疗的伦理问题及对策探讨[J].医学与哲学, 2012, 33(5):23-24, 58.
19.	杨灿, 郭鑫, 谢军.基因治疗技术的伦理思考[J].中国医学伦理学, 2013, 26(3):331-333.
20.	YAN Fei, GOU Lantu, YANG Jinliang, et al. A novel pro-apoptosis gene PNAS4 that induces apoptosis in A549 human lung adenocarcinoma cells and inhibits tumor growth in mice[J]. Biochimie, 2009, 91(4):502-507.
21.	HOU Shengyan, ZHAO Zhiwei, YAN Fei, et al. Genetic transfer of PNAS-4 induces apoptosis and enhances sensitivity to gemcitabine in lung cancer[J]. Cell Biol Int, 2009, 33(3):276-282.
22.	曾辉, 石华山, 李志平.人凋亡相关新基因PNAS-4与放射联合治疗Lewis肺癌的实验研究[J].华西医学, 2009, 24(4):926-929.
23.	YANG F, LI Z Y, DENG H X, et al. Efficient inhibition of ovarian cancer growth and prolonged survival by transfection with a novel pro-apoptotic gene, hPNAS-4, in a mouse model. In vivo and in vitro results[J]. Oncology, 2008, 75(3-4):137-144.
24.	YUAN Zhu, LIU Huanyi, YAN Fei, et al. Improved therapeutic efficacy against murine carcinoma by combining honokiol with gene therapy of PNAS-4, a novel pro-apoptotic gene[J]. Cancer Sci, 2009, 100(9):1757-1766.
25.	YUAN Zhu, YAN Fei, WANG Yongsheng, et al. PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin[J]. Cancer Chemother Pharmacol, 2009, 65(1):13-25.
26.	YAN Fei, QIAN Meilin, YANG Fan, et al. A novel pro-apoptosis protein PNAS-4 from Xenopus laevis: cloning, expression, purification, and polyclonal antibody production[J]. Biochemistry (Moscow), 2007, 72(6):664-671.
27.	ZHOU Bin, YAN Hui, LI Yuan, et al. PNAS-4 expression and its relationship to p53 in colorectal cancer[J]. Mol Biol Rep, 2012, 39(1):243-249.
28.	蒲俏虹, 吴清清, 金小宝, 等.格列卫激活caspase-3诱导K562细胞凋亡[J].药学学报, 2014, 49(8):1124-1129.
29.	庄严, 王丹丹, 柳忠兰, 等.吸烟对大鼠局灶性脑缺血后Caspase-3表达及细胞凋亡的影响[J].中国老年学杂志, 2014(1):156-158.
30.	韩凤, 李丛言, 关雪莲, 等.大鼠脑出血周边组织caspase-3表达和细胞凋亡的变化及促红细胞生成素的影响[J].中风与神经疾病杂志, 2013, 30(8):707-709.
31.	付霞.经鼻腔给予IGF-1对缺血缺氧性脑损伤大鼠caspase-3表达和细胞凋亡的影响[J].航空航天医学杂志, 2014, 25(1):8-9.
32.	GOU Lantu, TONG Aiping, YAN Fei, et al. Altered protein-expressing profile in hPNAS4-induced apoptosis in A549 human lung adenocarcinoma cells[J]. J Cell Biochem, 2009, 108(5):1211-1219.
33.	林哲, 邓玮明, 何娅娣, 等.膀胱移行细胞癌组织中前胸腺素α的表达及其临床意义[J].临床泌尿外科杂志, 2012, 27(8):598-600.
34.	张卓梅, 何飞.前胸腺素α在人卵巢癌中的表达、分布及其与肿瘤分级的相关性[J].中国生物制品学杂志, 2012, 25(7):888-891.
35.	刘爱凤, 程爱兰.膜联蛋白A1及其与肿瘤关系的研究进展[J].现代生物医学进展, 2013, 13(13):2590-2592, 2524.
36.	刘清华, 朱明华.膜联蛋白A1与恶性肿瘤的关系[J].临床与实验病理学杂志, 2012, 28(5):556-558.
37.	梁博伟, 赵劲民, 殷国前, 等.膜联蛋白A1生理功能的研究进展[J].蛇志, 2012, 24(2):160-162.
38.	杜亚丽, 吕蓓.ANXA1, Ki-67抗原在宫颈上皮内瘤变和宫颈癌中的表达及其相互关系[J].现代肿瘤医学, 2014, 22(6):1398-1402.
39.	杨华, 廖国玲, 杨风琴, 等.ANXA1在胃癌中的表达及其临床意义[J].现代检验医学杂志, 2013, 28(6):63-64, 68.
40.	李红玲, 沈涛, 撒亚莲, 等.膜联蛋白A1在非小细胞肺癌组织中的表达及意义[J].中国肿瘤临床, 2013, 40(15):907-910.
41.	SHIN E J, SHIN H M, NAM E, et al. DeSUMOylating isopeptidase:a second class of SUMO protease[J]. EMBO Rep, 2012, 13(4):339-346.
42.	SUH H Y, KIM J H, WOO J S, et al. Crystal structure of DeSI-1, a novel deSUMOylase belonging to a putative isopeptidase superfamily[J]. Proteins, 2012, 80(8):2099-2104.
43.	DROESCHER M, CHAUGULE V K, PICHLER A. SUMO rules:regulatory concepts and their implication in neurologic functions[J]. Neuromolecular Med, 2013, 15(4):639-660.
44.	初冰, 陈禹先.SUMO化修饰的研究进展[J].天津农业科学, 2013, 19(10):26-27.
45.	蒋华东, 李钰.SUMO化修饰在DNA损伤响应中的作用[J].中国细胞生物学学报, 2012, 34(10):1049-1054.
46.	汪小杰, 毛若雨, 张勇, 等.SUMO在蛋白表达中的应用[J].生物技术通报, 2013, (10):28-33.
47.	程金科, 左勇.去SUMO化蛋白酶的生物学功能与作用基础研究[J].上海交通大学学报:医学版, 2012, 32(9):1117-1121.
48.	赵怡超, 卜军, 何奔.SUMO化修饰在核受体功能调控中的作用[J].生理科学进展, 2013, 44(4):287-290.
49.	龚爱华, 熊二梦, 张严, 等.SAHA诱导的p21表达致U251MG细胞抗凋亡效应[J].中国药理学通报, 2013, 29(12):1743-1747.
50.	易玲, 邱荣元, 王松柏, 等.原发性肝细胞癌组织中P21的亚细胞定位及其意义[J].实用癌症杂志, 2013, 28(6):593-595, 598.

1. 董少婷, 杨红丽, 王爽.细胞凋亡在正常和肿瘤组织微环境中的作用[J].国际肿瘤学杂志, 2013, 40(2):92-95.
2. 王贲士, 陈德喜, 郭洪亮.自噬与肿瘤的研究现状[J].中华肿瘤防治杂志, 2014, 21(8):637-640.
3. 李玲, 徐小洁, 叶棋浓.细胞自噬与肿瘤[J].中国生物化学与分子生物学报, 2013, 29(11):995-1001.
4. 武晓燕, 侯玲玲, 晏琼, 等.凋亡素诱导细胞凋亡的机制及其在肿瘤治疗中的应用[J].生理科学进展, 2014, 45(1):45-48.
5. 聂雪坤, 张舒晟, 史道华.调控肿瘤细胞自噬相关分子的研究进展[J].国际肿瘤学杂志, 2013, 40(11):803-806.
6. 丁坚, 蔡军.P53、XIAP与细胞凋亡的关系及其靶向的细胞凋亡在肿瘤治疗中的研究进展[J].实用临床医学, 2013, 14(1):127-130.
7. 王剑龙, 郭刚文, 孙剑锋, 等.促凋亡基因PUMA的研究进展及其与肿瘤的关系[J].中国医药指南, 2013, 11(3):50-52.
8. YAO Shaohua, XIE Lifang, QIAN Meilin, et al. Pnas4 is a novel regulator for convergence and extension during vertebrate gastrulation[J]. FEBS Lett, 2008, 582(15):2325-2332.
9. YAN Fei, RUAN Xuzhi, YANG Hanshuo, et al. Identification, characterization, and effects of Xenopus laevis PNAS-4 gene on embryonic development[J]. J Biomed Biotechnol, 2010, 2010:Article ID 134764.
10. 张木子荷, 武鑫, 张丽娟, 等.经修饰的聚阳离子载体在基因治疗中的应用进展[J].药学服务与研究, 2013, 13(1):25-29.
11. 梁迎春, 程龙, 叶棋浓.肿瘤基因治疗的研究进展[J].生物技术通讯, 2012, 23(3):436-439, 460.
12. 王飞, 赵海平.胰腺癌的基因治疗进展[J].中国疗养医学, 2012, 21(5):413-416.
13. 赵嵘, 张锡朋.结直肠肿瘤生物治疗的研究进展[J].继续医学教育, 2014, 28(6):51-54.
14. 王文涛, 秦建军.基因修饰的间充质干细胞在肺部肿瘤治疗中的前景与障碍[J].医药论坛杂志, 2014, 35(3):141-143.
15. 钟林, 李强, 陈飞, 等.结直肠癌基因治疗研究进展[J].岭南现代临床外科, 2014, 14(2):207-210.
16. 宋向明, 赵瑜, 田长富.肿瘤基因治疗的病毒载体研究进展[J].医学综述, 2014, 20(6):1006-1009.
17. 莱智勇, 徐钧.肝癌的基因治疗[J].中国药物与临床, 2014, 14(3):327-330.
18. 安娜, 王忠彦.基因治疗的伦理问题及对策探讨[J].医学与哲学, 2012, 33(5):23-24, 58.
19. 杨灿, 郭鑫, 谢军.基因治疗技术的伦理思考[J].中国医学伦理学, 2013, 26(3):331-333.
20. YAN Fei, GOU Lantu, YANG Jinliang, et al. A novel pro-apoptosis gene PNAS4 that induces apoptosis in A549 human lung adenocarcinoma cells and inhibits tumor growth in mice[J]. Biochimie, 2009, 91(4):502-507.
21. HOU Shengyan, ZHAO Zhiwei, YAN Fei, et al. Genetic transfer of PNAS-4 induces apoptosis and enhances sensitivity to gemcitabine in lung cancer[J]. Cell Biol Int, 2009, 33(3):276-282.
22. 曾辉, 石华山, 李志平.人凋亡相关新基因PNAS-4与放射联合治疗Lewis肺癌的实验研究[J].华西医学, 2009, 24(4):926-929.
23. YANG F, LI Z Y, DENG H X, et al. Efficient inhibition of ovarian cancer growth and prolonged survival by transfection with a novel pro-apoptotic gene, hPNAS-4, in a mouse model. In vivo and in vitro results[J]. Oncology, 2008, 75(3-4):137-144.
24. YUAN Zhu, LIU Huanyi, YAN Fei, et al. Improved therapeutic efficacy against murine carcinoma by combining honokiol with gene therapy of PNAS-4, a novel pro-apoptotic gene[J]. Cancer Sci, 2009, 100(9):1757-1766.
25. YUAN Zhu, YAN Fei, WANG Yongsheng, et al. PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin[J]. Cancer Chemother Pharmacol, 2009, 65(1):13-25.
26. YAN Fei, QIAN Meilin, YANG Fan, et al. A novel pro-apoptosis protein PNAS-4 from Xenopus laevis: cloning, expression, purification, and polyclonal antibody production[J]. Biochemistry (Moscow), 2007, 72(6):664-671.
27. ZHOU Bin, YAN Hui, LI Yuan, et al. PNAS-4 expression and its relationship to p53 in colorectal cancer[J]. Mol Biol Rep, 2012, 39(1):243-249.
28. 蒲俏虹, 吴清清, 金小宝, 等.格列卫激活caspase-3诱导K562细胞凋亡[J].药学学报, 2014, 49(8):1124-1129.
29. 庄严, 王丹丹, 柳忠兰, 等.吸烟对大鼠局灶性脑缺血后Caspase-3表达及细胞凋亡的影响[J].中国老年学杂志, 2014(1):156-158.
30. 韩凤, 李丛言, 关雪莲, 等.大鼠脑出血周边组织caspase-3表达和细胞凋亡的变化及促红细胞生成素的影响[J].中风与神经疾病杂志, 2013, 30(8):707-709.
31. 付霞.经鼻腔给予IGF-1对缺血缺氧性脑损伤大鼠caspase-3表达和细胞凋亡的影响[J].航空航天医学杂志, 2014, 25(1):8-9.
32. GOU Lantu, TONG Aiping, YAN Fei, et al. Altered protein-expressing profile in hPNAS4-induced apoptosis in A549 human lung adenocarcinoma cells[J]. J Cell Biochem, 2009, 108(5):1211-1219.
33. 林哲, 邓玮明, 何娅娣, 等.膀胱移行细胞癌组织中前胸腺素α的表达及其临床意义[J].临床泌尿外科杂志, 2012, 27(8):598-600.
34. 张卓梅, 何飞.前胸腺素α在人卵巢癌中的表达、分布及其与肿瘤分级的相关性[J].中国生物制品学杂志, 2012, 25(7):888-891.
35. 刘爱凤, 程爱兰.膜联蛋白A1及其与肿瘤关系的研究进展[J].现代生物医学进展, 2013, 13(13):2590-2592, 2524.
36. 刘清华, 朱明华.膜联蛋白A1与恶性肿瘤的关系[J].临床与实验病理学杂志, 2012, 28(5):556-558.
37. 梁博伟, 赵劲民, 殷国前, 等.膜联蛋白A1生理功能的研究进展[J].蛇志, 2012, 24(2):160-162.
38. 杜亚丽, 吕蓓.ANXA1, Ki-67抗原在宫颈上皮内瘤变和宫颈癌中的表达及其相互关系[J].现代肿瘤医学, 2014, 22(6):1398-1402.
39. 杨华, 廖国玲, 杨风琴, 等.ANXA1在胃癌中的表达及其临床意义[J].现代检验医学杂志, 2013, 28(6):63-64, 68.
40. 李红玲, 沈涛, 撒亚莲, 等.膜联蛋白A1在非小细胞肺癌组织中的表达及意义[J].中国肿瘤临床, 2013, 40(15):907-910.
41. SHIN E J, SHIN H M, NAM E, et al. DeSUMOylating isopeptidase:a second class of SUMO protease[J]. EMBO Rep, 2012, 13(4):339-346.
42. SUH H Y, KIM J H, WOO J S, et al. Crystal structure of DeSI-1, a novel deSUMOylase belonging to a putative isopeptidase superfamily[J]. Proteins, 2012, 80(8):2099-2104.
43. DROESCHER M, CHAUGULE V K, PICHLER A. SUMO rules:regulatory concepts and their implication in neurologic functions[J]. Neuromolecular Med, 2013, 15(4):639-660.
44. 初冰, 陈禹先.SUMO化修饰的研究进展[J].天津农业科学, 2013, 19(10):26-27.
45. 蒋华东, 李钰.SUMO化修饰在DNA损伤响应中的作用[J].中国细胞生物学学报, 2012, 34(10):1049-1054.
46. 汪小杰, 毛若雨, 张勇, 等.SUMO在蛋白表达中的应用[J].生物技术通报, 2013, (10):28-33.
47. 程金科, 左勇.去SUMO化蛋白酶的生物学功能与作用基础研究[J].上海交通大学学报:医学版, 2012, 32(9):1117-1121.
48. 赵怡超, 卜军, 何奔.SUMO化修饰在核受体功能调控中的作用[J].生理科学进展, 2013, 44(4):287-290.
49. 龚爱华, 熊二梦, 张严, 等.SAHA诱导的p21表达致U251MG细胞抗凋亡效应[J].中国药理学通报, 2013, 29(12):1743-1747.
50. 易玲, 邱荣元, 王松柏, 等.原发性肝细胞癌组织中P21的亚细胞定位及其意义[J].实用癌症杂志, 2013, 28(6):593-595, 598.

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