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, 楊紅麗, 王爽.細胞凋亡在正常和腫瘤組織微環境中的作用[J].國際腫瘤學雜志, 2013, 40(2):92-95.
2.	王賁士, 陳德喜, 郭洪亮.自噬與腫瘤的研究現狀[J].中華腫瘤防治雜志, 2014, 21(8):637-640.
3.	李玲, 徐小潔, 葉棋濃.細胞自噬與腫瘤[J].中國生物化學與分子生物學報, 2013, 29(11):995-1001.
4.	武曉燕, 侯玲玲, 晏瓊, 等.凋亡素誘導細胞凋亡的機制及其在腫瘤治療中的應用[J].生理科學進展, 2014, 45(1):45-48.
5.	聶雪坤, 張舒晟, 史道華.調控腫瘤細胞自噬相關分子的研究進展[J].國際腫瘤學雜志, 2013, 40(11):803-806.
6.	丁堅, 蔡軍.P53、XIAP與細胞凋亡的關系及其靶向的細胞凋亡在腫瘤治療中的研究進展[J].實用臨床醫學, 2013, 14(1):127-130.
7.	王劍龍, 郭剛文, 孫劍鋒, 等.促凋亡基因PUMA的研究進展及其與腫瘤的關系[J].中國醫藥指南, 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.	張木子荷, 武鑫, 張麗娟, 等.經修飾的聚陽離子載體在基因治療中的應用進展[J].藥學服務與研究, 2013, 13(1):25-29.
11.	梁迎春, 程龍, 葉棋濃.腫瘤基因治療的研究進展[J].生物技術通訊, 2012, 23(3):436-439, 460.
12.	王飛, 趙海平.胰腺癌的基因治療進展[J].中國療養醫學, 2012, 21(5):413-416.
13.	趙嶸, 張錫朋.結直腸腫瘤生物治療的研究進展[J].繼續醫學教育, 2014, 28(6):51-54.
14.	王文濤, 秦建軍.基因修飾的間充質干細胞在肺部腫瘤治療中的前景與障礙[J].醫藥論壇雜志, 2014, 35(3):141-143.
15.	鐘林, 李強, 陳飛, 等.結直腸癌基因治療研究進展[J].嶺南現代臨床外科, 2014, 14(2):207-210.
16.	宋向明, 趙瑜, 田長富.腫瘤基因治療的病毒載體研究進展[J].醫學綜述, 2014, 20(6):1006-1009.
17.	萊智勇, 徐鈞.肝癌的基因治療[J].中國藥物與臨床, 2014, 14(3):327-330.
18.	安娜, 王忠彥.基因治療的倫理問題及對策探討[J].醫學與哲學, 2012, 33(5):23-24, 58.
19.	楊燦, 郭鑫, 謝軍.基因治療技術的倫理思考[J].中國醫學倫理學, 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.	曾輝, 石華山, 李志平.人凋亡相關新基因PNAS-4與放射聯合治療Lewis肺癌的實驗研究[J].華西醫學, 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, 吳清清, 金小寶, 等.格列衛激活caspase-3誘導K562細胞凋亡[J].藥學學報, 2014, 49(8):1124-1129.
29.	莊嚴, 王丹丹, 柳忠蘭, 等.吸煙對大鼠局灶性腦缺血后Caspase-3表達及細胞凋亡的影響[J].中國老年學雜志, 2014(1):156-158.
30.	韓鳳, 李叢言, 關雪蓮, 等.大鼠腦出血周邊組織caspase-3表達和細胞凋亡的變化及促紅細胞生成素的影響[J].中風與神經疾病雜志, 2013, 30(8):707-709.
31.	付霞.經鼻腔給予IGF-1對缺血缺氧性腦損傷大鼠caspase-3表達和細胞凋亡的影響[J].航空航天醫學雜志, 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, 鄧瑋明, 何婭娣, 等.膀胱移行細胞癌組織中前胸腺素α的表達及其臨床意義[J].臨床泌尿外科雜志, 2012, 27(8):598-600.
34.	張卓梅, 何飛.前胸腺素α在人卵巢癌中的表達、分布及其與腫瘤分級的相關性[J].中國生物制品學雜志, 2012, 25(7):888-891.
35.	劉愛鳳, 程愛蘭.膜聯蛋白A1及其與腫瘤關系的研究進展[J].現代生物醫學進展, 2013, 13(13):2590-2592, 2524.
36.	劉清華, 朱明華.膜聯蛋白A1與惡性腫瘤的關系[J].臨床與實驗病理學雜志, 2012, 28(5):556-558.
37.	梁博偉, 趙勁民, 殷國前, 等.膜聯蛋白A1生理功能的研究進展[J].蛇志, 2012, 24(2):160-162.
38.	杜亞麗, 呂蓓.ANXA1, Ki-67抗原在宮頸上皮內瘤變和宮頸癌中的表達及其相互關系[J].現代腫瘤醫學, 2014, 22(6):1398-1402.
39.	楊華, 廖國玲, 楊風琴, 等.ANXA1在胃癌中的表達及其臨床意義[J].現代檢驗醫學雜志, 2013, 28(6):63-64, 68.
40.	李紅玲, 沈濤, 撒亞蓮, 等.膜聯蛋白A1在非小細胞肺癌組織中的表達及意義[J].中國腫瘤臨床, 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, 陳禹先.SUMO化修飾的研究進展[J].天津農業科學, 2013, 19(10):26-27.
45.	蔣華東, 李鈺.SUMO化修飾在DNA損傷響應中的作用[J].中國細胞生物學學報, 2012, 34(10):1049-1054.
46.	汪小杰, 毛若雨, 張勇, 等.SUMO在蛋白表達中的應用[J].生物技術通報, 2013, (10):28-33.
47.	程金科, 左勇.去SUMO化蛋白酶的生物學功能與作用基礎研究[J].上海交通大學學報:醫學版, 2012, 32(9):1117-1121.
48.	趙怡超, 卜軍, 何奔.SUMO化修飾在核受體功能調控中的作用[J].生理科學進展, 2013, 44(4):287-290.
49.	龔愛華, 熊二夢, 張嚴, 等.SAHA誘導的p21表達致U251MG細胞抗凋亡效應[J].中國藥理學通報, 2013, 29(12):1743-1747.
50.	易玲, 邱榮元, 王松柏, 等.原發性肝細胞癌組織中P21的亞細胞定位及其意義[J].實用癌癥雜志, 2013, 28(6):593-595, 598.

1. 董少婷, 楊紅麗, 王爽.細胞凋亡在正常和腫瘤組織微環境中的作用[J].國際腫瘤學雜志, 2013, 40(2):92-95.
2. 王賁士, 陳德喜, 郭洪亮.自噬與腫瘤的研究現狀[J].中華腫瘤防治雜志, 2014, 21(8):637-640.
3. 李玲, 徐小潔, 葉棋濃.細胞自噬與腫瘤[J].中國生物化學與分子生物學報, 2013, 29(11):995-1001.
4. 武曉燕, 侯玲玲, 晏瓊, 等.凋亡素誘導細胞凋亡的機制及其在腫瘤治療中的應用[J].生理科學進展, 2014, 45(1):45-48.
5. 聶雪坤, 張舒晟, 史道華.調控腫瘤細胞自噬相關分子的研究進展[J].國際腫瘤學雜志, 2013, 40(11):803-806.
6. 丁堅, 蔡軍.P53、XIAP與細胞凋亡的關系及其靶向的細胞凋亡在腫瘤治療中的研究進展[J].實用臨床醫學, 2013, 14(1):127-130.
7. 王劍龍, 郭剛文, 孫劍鋒, 等.促凋亡基因PUMA的研究進展及其與腫瘤的關系[J].中國醫藥指南, 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. 張木子荷, 武鑫, 張麗娟, 等.經修飾的聚陽離子載體在基因治療中的應用進展[J].藥學服務與研究, 2013, 13(1):25-29.
11. 梁迎春, 程龍, 葉棋濃.腫瘤基因治療的研究進展[J].生物技術通訊, 2012, 23(3):436-439, 460.
12. 王飛, 趙海平.胰腺癌的基因治療進展[J].中國療養醫學, 2012, 21(5):413-416.
13. 趙嶸, 張錫朋.結直腸腫瘤生物治療的研究進展[J].繼續醫學教育, 2014, 28(6):51-54.
14. 王文濤, 秦建軍.基因修飾的間充質干細胞在肺部腫瘤治療中的前景與障礙[J].醫藥論壇雜志, 2014, 35(3):141-143.
15. 鐘林, 李強, 陳飛, 等.結直腸癌基因治療研究進展[J].嶺南現代臨床外科, 2014, 14(2):207-210.
16. 宋向明, 趙瑜, 田長富.腫瘤基因治療的病毒載體研究進展[J].醫學綜述, 2014, 20(6):1006-1009.
17. 萊智勇, 徐鈞.肝癌的基因治療[J].中國藥物與臨床, 2014, 14(3):327-330.
18. 安娜, 王忠彥.基因治療的倫理問題及對策探討[J].醫學與哲學, 2012, 33(5):23-24, 58.
19. 楊燦, 郭鑫, 謝軍.基因治療技術的倫理思考[J].中國醫學倫理學, 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. 曾輝, 石華山, 李志平.人凋亡相關新基因PNAS-4與放射聯合治療Lewis肺癌的實驗研究[J].華西醫學, 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, 吳清清, 金小寶, 等.格列衛激活caspase-3誘導K562細胞凋亡[J].藥學學報, 2014, 49(8):1124-1129.
29. 莊嚴, 王丹丹, 柳忠蘭, 等.吸煙對大鼠局灶性腦缺血后Caspase-3表達及細胞凋亡的影響[J].中國老年學雜志, 2014(1):156-158.
30. 韓鳳, 李叢言, 關雪蓮, 等.大鼠腦出血周邊組織caspase-3表達和細胞凋亡的變化及促紅細胞生成素的影響[J].中風與神經疾病雜志, 2013, 30(8):707-709.
31. 付霞.經鼻腔給予IGF-1對缺血缺氧性腦損傷大鼠caspase-3表達和細胞凋亡的影響[J].航空航天醫學雜志, 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, 鄧瑋明, 何婭娣, 等.膀胱移行細胞癌組織中前胸腺素α的表達及其臨床意義[J].臨床泌尿外科雜志, 2012, 27(8):598-600.
34. 張卓梅, 何飛.前胸腺素α在人卵巢癌中的表達、分布及其與腫瘤分級的相關性[J].中國生物制品學雜志, 2012, 25(7):888-891.
35. 劉愛鳳, 程愛蘭.膜聯蛋白A1及其與腫瘤關系的研究進展[J].現代生物醫學進展, 2013, 13(13):2590-2592, 2524.
36. 劉清華, 朱明華.膜聯蛋白A1與惡性腫瘤的關系[J].臨床與實驗病理學雜志, 2012, 28(5):556-558.
37. 梁博偉, 趙勁民, 殷國前, 等.膜聯蛋白A1生理功能的研究進展[J].蛇志, 2012, 24(2):160-162.
38. 杜亞麗, 呂蓓.ANXA1, Ki-67抗原在宮頸上皮內瘤變和宮頸癌中的表達及其相互關系[J].現代腫瘤醫學, 2014, 22(6):1398-1402.
39. 楊華, 廖國玲, 楊風琴, 等.ANXA1在胃癌中的表達及其臨床意義[J].現代檢驗醫學雜志, 2013, 28(6):63-64, 68.
40. 李紅玲, 沈濤, 撒亞蓮, 等.膜聯蛋白A1在非小細胞肺癌組織中的表達及意義[J].中國腫瘤臨床, 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, 陳禹先.SUMO化修飾的研究進展[J].天津農業科學, 2013, 19(10):26-27.
45. 蔣華東, 李鈺.SUMO化修飾在DNA損傷響應中的作用[J].中國細胞生物學學報, 2012, 34(10):1049-1054.
46. 汪小杰, 毛若雨, 張勇, 等.SUMO在蛋白表達中的應用[J].生物技術通報, 2013, (10):28-33.
47. 程金科, 左勇.去SUMO化蛋白酶的生物學功能與作用基礎研究[J].上海交通大學學報:醫學版, 2012, 32(9):1117-1121.
48. 趙怡超, 卜軍, 何奔.SUMO化修飾在核受體功能調控中的作用[J].生理科學進展, 2013, 44(4):287-290.
49. 龔愛華, 熊二夢, 張嚴, 等.SAHA誘導的p21表達致U251MG細胞抗凋亡效應[J].中國藥理學通報, 2013, 29(12):1743-1747.
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