肿瘤基因信使RNA可变剪接及其应用

摘要/Abstract

摘要：可变剪接作为基因的一种修饰方式，是真核细胞表达调控过程的重要因素。它使同一蛋白质编码基因能够产生多种转录本，极大地扩展了遗传信息的应用。在人类肿瘤细胞中前体信使RNA的可变剪接扮演着重要角色，一些重要基因通过可变剪接产生不同于正常细胞中的剪接异构体。这些肿瘤特异性剪接异构体的存在导致了肿瘤的发生、发展。深入探索肿瘤相关基因的可变剪接对肿瘤的诊断、治疗具有重要意义。

关键词:肿瘤,RNA,信使,可变剪接

Abstract:As a way of gene modification, alternative splicing is an important factor of eukaryotic gene expression and regulation. It makes various transcripts from one proteincoding gene, and greatly extends the genetic information. Alternative splicing of premessenger RNA plays an important role in tumor cells. By alternative splicing, some important genes can generate splicing variants different from those in normal cells. The existence of tumorspecific splicing variants leads to the occurrence and progression of tumor. Therefore, exploration on the alternative splicing of tumorassociated genes may be of great significance in tumor diagnosis and treatment.

Key words:Neoplasms,RNA, messenger,Alternative splicing

张鑫桐,岳文涛. 肿瘤基因信使RNA可变剪接及其应用[J]. 国际肿瘤学杂志, 2014, 41(8): 648-651.

Zhang Xintong, Yue Wentao. Alternative splicing of tumor associated genes messenger RNA and application[J]. Journal of International Oncology, 2014, 41(8): 648-651.

参考文献

［1］ Gilbert W. Why genes in pieces?［J］. Nature, 1978, 271(5645): 501. ［2］ Berget SM, Moore C, Sharp PA. Spliced segments at the 5′ terminus of adenovirus 2 late mRNA［J］. Proc Natl Acad Sci USA, 1977, 74(8): 3171-3175. ［3］ Wang ET, Sandberg R, Luo S, et al. Alternative isoform regulation in human tissue transcriptomes［J］. Nature, 2008, 456(7221): 470-476. ［4］ Dammann R, Li C, Yoon JH, et al. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3［J］. Nat Genet, 2000, 25(3): 315-319. ［5］ Foley CJ, Freedman H, Choo SL, et al. Dynamics of RASSF1A/MOAP1 association with death receptors［J］. Mol Cell Biol, 2008, 28(14): 4520-4535. ［6］ Guo C, Zhang X, Pfeifer GP. The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20like kinases MST1 and MST2［J］. J Biol Chem, 2011, 286(8): 6253-6261. ［7］ Reeves ME, Baldwin ML, Aragon R, et al. RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1［J］. BMC Res Notes, 2012, 5: 239. ［8］ Reeves ME, Firek M, Chen ST, et al. The RASSF1 gene and the opposing effects of the RASSF1A and RASSF1C isoforms on cell proliferation and apoptosis［J］. Mol Biol Int, 2013, 2013: 145096. ［9］ Arribas J, Baselga J, Pedersen K, et al. p95HER2 and breast cancer［J］. Cancer Res, 2011, 71(5): 1515-1519. ［10］ Pedersen K, Angelini PD, Laos S, et al. A naturally occurring HER2 carboxyterminal fragment promotes mammary tumor growth and metastasis［J］. Mol Cell Biol, 2009, 29(12): 3319-3331. ［11］ Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data［J］. Cancer Discov, 2012, 2(5): 401-404. ［12］ Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal［J］. Sci Signal, 2013, 6(269): pl1. ［13］ Valent A, PenaultLlorca F, Cayre A, et al. Change in HER2 (ERBB2) gene status after taxanebased chemotherapy for breast cancer: polyploidization can lead to diagnostic pitfalls with potential impact for clinical management［J］. Cancer Genet, 2013, 206(12): 37-41. ［14］Harbeck N, Pegram MD, Rüschoff J, et al. Targeted therapy in metastatic breast cancer: the HER2/neu oncogene［J］. Breast Care (Basel), 2010, 5(s1): 3-7. ［15］Jackson C, Browell D, Gautrey H, et al. Clinical significance of HER2 splice variants in breast cancer progression and drug resistance［J］. Int J Cell Biol, 2013, 2013: 973584. ［16］Mitra D, Brumlik MJ, Okamgba SU, et al. An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance［J］. Mol Cancer Ther, 2009, 8(8): 2152-2162. ［17］Marchini C, Gabrielli F, Iezzi M, et al. The human splice variant Δ16HER2 induces rapid tumor onset in a reporter transgenic mouse［J］. PLoS One, 2011, 6(4): e18727. ［18］Pedersen K, Angelini PD, Laos S, et al. A naturally occurring HER2 carboxyterminal fragment promotes mammary tumor growth and metastasis［J］. Mol Cell Biol, 2009, 29(12): 3319-3331. ［19］Makino H, Iraha M, Manba N, et al. Utility of serum human epidermal growth factor receptor2 extracellular domain(HER2 ECD)assessment in patients with advanced or recurrent breast cancer and those who received neoadjuvant therapy［J］. Gan To Kagaku Ryoho, 2012, 39(2): 237-240. ［20］Leary AF, Hanna WM, van de Vijver MJ, et al. Value and limitations of measuring HER2 extracellular domain in the serum of breast cancer patients［J］. J Clin Oncol, 2009, 27(10): 1694-1705. ［21］Koletsa T, Kostopoulos I, Charalambous E, et al. A splice variant of HER2 corresponding to Herstatin is expressed in the noncancerous breast and in breast carcinomas［J］. Neoplasia, 2008, 10(7): 687-696. ［22］Bauman JA, Li SD, Yang A, et al. Antitumor activity of spliceswitching oligonucleotides［J］. Nucleic Acids Res, 2010, 38(22): 8348-8356. ［23］刘艳红, 赵艳洁, 房淑娟, 等. 肝癌相关基因的分子克隆和可变剪切分析［J］. 中南大学学报（医学版）, 2013(9): 869-875. ［24］Won YS, Lee SW. Selective regression of cancer cells expressing a splicing variant of AIMP2 through targeted RNA replacement by transsplicing ribozyme［J］. J Biotechnol, 2012, 158(12): 44-49. ［25］Choi JW, Kim DG, Lee AE, et al. Cancerassociated splicing variant of tumor suppressor AIMP2/p38: pathological implication in tumorigenesis［J］. PLoS Genet, 2011, 7(3): e1001351. ［26］Chang WH, Liu TC, Yang WK, et al. Amiloride modulates alternative splicing in leukemic cells and resensitizes BcrAblT315I mutant cells to imatinib［J］. Cancer Res, 2011, 71(2): 383-392. ［27］Wan J, Sazani P, Kole R. Modification of HER2 premRNA alternative splicing and its effects on breast cancer cells［J］. Int J Cancer, 2009, 124(4): 772-777. ［28］Wang Y, Cheong CG, Hall TM, et al. Engineering splicing factors with designed specificities［J］. Nat Methods, 2009, 6(11): 825-830. ［29］Christofk HR, Vander Heiden MG, Harris MH, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth［J］. Nature, 2008, 452(7184): 230-233.

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