Abstract
Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (IncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
概 要
多聚嘧啶区结合蛋白 1 (PTBP1) 在多种疾病, 尤其是在某些癌症中发挥作用. 为明确 PTBP1 在人体的生物学功能, 本文汇总了调控 PTBP1 相关的 miRNA、 长链非编码 RNA (lncRNA)和 RNA 结合蛋白. 另外, 我们重点阐述了 PTBP1 充当糖酵解、 细胞凋亡、 增殖、 肿瘤发生、 侵袭和迁移的调节剂, 并为制定有用的癌症治疗策略做出了潜在贡献.
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References
Aldave G, Gonzalez-Huarriz M, Rubio A, et al., 2018. The aberrant splicing of BAF45d links splicing regulation and transcription in glioblastoma. Neuro-Oncology, 20(7): 930–941. https://doi.org/10.1093/neuonc/noy007
Attig J, Agostini F, Gooding C, et al., 2018. Heteromeric RNP assembly at LINEs controls lineage-specific RNA processing. Cell, 174(5): 1067–1081.el7. https://doi.org/10.1016/jxell.2018.07.001
Barbagallo D, Caponnetto A, Cirnigliaro M, et al., 2018. CircSMARCA5 inhibits migration of glioblastoma multiforme cells by regulating a molecular axis involving splicing factors SRSF1/SRSF3/PTB. Int J MolSci, 19(2): 480. https://doi.org/10.3390/ijms19020480
Black DL, 2003. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem, 72:291–336. https://doi.org/10.1146/annurev.biochem.72.121801.161720
Brown CE, Mackall CL, 2019. CAR T cell therapy: inroads to response and resistance. Nat Rev Immunol, 19(2):73–74. https://doi.org/10.1038/s41577-018-0119-y
Bubenik J, Swanson MS, 2018. Strring up cancer with IncRNA. Mol Cell, 72(3):399–401. https://doi.org/10.1016/j.molcel.2018.10.026
Busch A, Hertel KJ, 2012. Evolution of SR protein and hnRNP splicing regulatory factors. Wiley Interdiscip Rev RNA, 3(1):1–12. https://doi.org/10.1002/wrna.100
Calabretta S, Bielli P, Passacantilli I, et al., 2016. Modulation of PKM alternative splicing by PTBP1 promotes gem-citabine resistance in pancreatic cancer cells. Oncogene, 35(16):2031–2039. https://doi.org/10.1038/onc.2015.270
Caruso P, Dunmore BJ, Schlosser K, et al., 2017. Identification of microRNA-124 as a major regulator of enhanced endothelial cell glycolysis in pulmonary arterial hypertension via PTBP1 (polypyrimidine tract binding protein) and pyruvate kinase M2. Circulation, 136(25):2451–2467. https://doi.org/10.1161/circulationaha.117.028034
Cheung HC, Hai T, Zhu W, et al, 2009. Splicing factors PTBP1 and PTBP2 promote proliferation and migration of glioma cell lines. Brain, 132(8):2277–2288. https://doi.org/10.1093/brain/awpl53
Corrionero A, Valcarcel J, 2009. RNA processing: redrawing the map of charted territory. Mol Cell, 36(6):918–919. https://doi.org/10.1016/j.molcel.2009.12.004
Cote GJ, Zhu W, Thomas A, et al., 2012. Hydrogen peroxide alters splicing of soluble guanylyl cyclase and selectively modulates expression of splicing regulators in human cancer cells. PLoS ONE, 7(7):e41099. https://doi.org/10.1371/journal.pone.0041099
Cui J, Placzek WJ, 2016. PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antit-ubulin chemotherapeutics. Cell Death Differ, 23(10): 1681–1690. https://doi.org/10.1038/cdd.2016.60
del Rio-Moreno M, Alors-Perez E, Gonzalez-Rubio S, et al., 2019. Dysregulation of the splicing machinery is associated to the development of non-alcoholic fatty liver disease. J Clin Endocrinol Metab, 104(8):3389–3402. https://doi.org/10.1210/jc.2019-00021
Domingues RG, Lago-Baldaia I, Pereira-Castro I, et al., 2016. CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204. Eur J Immunol, 46(6):1490–1503. https://doi.org/10.1002/eji.201545663
Dou XM, Zhang XS, 2016. RNA-binding protein PTB in spermatogenesis: progress in studies. Nat J Androl, 22(9): 856–860 (in Chinese). https://doi.org/10.13263/j.cnki.nja.2016.09.017
Ehehalt F, Knoch K, Erdmann K, et al., 2010. Impaired insulin turnover in islets from type 2 diabetic patients. Islets, 2(1):30–36. https://doi.org/10.4161/isL2.L10098
Ferrarese R, Harsh IV GR, Yadav AK, et al., 2014. Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression. J Clin Invest, 124(7): 2861–2876. https://doi.org/10.1172/jci68836
Finney OC, Brakke H, Rawlings-Rhea S, et al., 2019. CD19 CAR T cell product and disease attributes predict leukemia remission durability. J Clin Invest, 129(5):2123–2132. https://doi.org/10.1172/jcil25423
Fu XD, Ares M Jr, 2014. Context-dependent control of alternative splicing by RNA-binding proteins. Nat Rev Genet, 15(10):689–701. https://doi.org/10.1038/nrg3778
Ge ZY, Quek BL, Beemon KL, et al., 2016. Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway. eLife, 5:e11155. https://doi.org/10.7554/eLife.11155
Georgilis A, Klotz S, Hanley CJ, et al., 2018. PTBP1-mediated alternative splicing regulates the inflammatory secretome and the pro-tumorigenic effects of senescent cells. Cancer Cell, 34(1):85–102.e9. https://doi.org/10.1016/jxcell.2018.06.007
Ghetti A, Pinol-Roma S, Michael WM, et al., 1992. hnRNP 1, the polyprimidine tract-binding protein: distinct nuclear localization and association with hnRNAs. Nucleic Acids Res, 20(14): 3671–3678. https://doi.org/10.1093/nar/20.14.3671
Grammatikakis I, Gorospe M, 2016. Identification of neural stem cell differentiation repressor complex Pnky-FTBF1. Stem Cell Investig, 3:10. https://doi.org/10.21037/sci.2016.03.05
Guo JH, Jia J, Jia R, 2015. PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells. Sci Rep, 5(1): 14548. https://doi.org/10.1038/srep14548
Hamid FM, Makeyev EV, 2017. A mechanism underlying position-specific regulation of alternative splicing. Nucleic Acids Res, 45(21): 12455–12468. https://doi.org/10.1093/nar/gkx901
Han W, Wang L, Yin B, et al., 2014. Characterization of a novel posttranslational modification in polypyrimidine tract-binding proteins by SUMO1. BMB Rep, 47(4):233–238. https://doi.org/10.5483/bmbrep.2014.47.4.140
He X, Arslan AD, Ho TT, et al., 2014. Involvement of polypyrimidine tract-binding protein (PTBP1) in maintaining breast cancer cell growth and malignant properties. Oncogenesis, 3(1):e84. https://doi.org/10.1038/oncsis.2013.47
He XL, Yuan CF, Yang XL, 2015. Regulation and functional significance of CDC42 alternative splicing in ovarian cancer. Oncotarget, 6(30):29651–29663. https://doi.org/10.18632/oncotarget.4865
Hollander D, Donyo M, Atias N, et al., 2016. A network-based analysis of colon cancer splicing changes reveals a tumorigenesis-favoring regulatory pathway emanating from ELK1. Genome Res, 26(4):541–553. https://doi.org/10.1101/gr.193169.115
Hwang SR, Murga-Zamalloa C, Brown N, et al., 2017. Py-rimidine tract-binding protein 1 mediates pyruvate kinase M2-dependent phosphorylation of signal transducer and activator of transcription 3 and oncogenesis in anaplastic large cell lymphoma. Lab Invest, 97(8): 962–970. https://doi.org/10.1038/labinvest.2017.39
Iwai Y, Hamanishi J, Chamoto K, et al., 2017. Cancer immunotherapies targeting the PD-1 signaling pathway. J Biomed Sci, 24(1):26. https://doi.org/10.1186/s12929-017-0329-9
Izaguirre DI, Zhu W, Hai T, et al., 2012. PTBP1-dependent regulation of USP5 alternative RNA splicing plays a role in glioblastoma tumorigenesis. Mol Carcinog, 51(11): 895–906. https://doi.org/10.1002/mc.20859
Jeong DE, Heo S, Han JH, et al., 2018. Glucose controls the expression of polypyrimidine tract-binding protein 1 via the insulin receptor signaling pathway in pancreatic ß cells. Mol Cells, 41(10):909–916. https://doi.org/10.14348/molcells.2018.0147
Jiang JY, Chen X, Liu H, et al., 2017. Polypyrimidine tract-binding protein 1 promotes proliferation, migration and invasion in clear-cell renal cell carcinoma by regulating alternative splicing of PKM. Am J Cancer Res, 7(2): 245–259.
Jo YK, Roh SA, Lee H, et al., 2017. Polypyrimidine tract-binding protein 1-mediated down-regulation of ATG10 facilitates metastasis of colorectal cancer cells. Cancer Lett, 385: 21–27. https://doi.org/10.1016/j.canlet.2016.11.002
Juan WC, Roca X, Ong ST, 2014. Identification of cw-acting elements and splicing factors involved in the regulation of BLM pre-mRNA splicing. PLoS ONE, 9(4):e95210. https://doi.org/10.1371/journal.pone.0095210
Kang K, Peng X, Zhang X, et al., 2013. MicroRNA-124 suppresses the transactivation of nuclear factor of activated T cells by targeting multiple genes and inhibits the proliferation of pulmonary artery smooth muscle cells. J Biol Chem, 288(35):25414–25427. https://doi.org/10.1074/jbc.M113.460287
Keppetipola N, Sharma S, Li Q, et al., 2012. Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Crit Rev Biochem Mol Biol, 47(4):360–378. https://doi.org/10.3109/10409238.2012.691456
Kumazaki M, Shinohara H, Taniguchi K, et al., 2016. Perturbation of the Warburg effect increases the sensitivity of cancer cells to trail-induced cell death. Exp Cell Res, 347(1):133–142. https://doi.org/10.1016/j.yexcr.2016.07.022
la Porta J, Matus-Nicodemos R, Valentin-Acevedo A, et al., 2016. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1) is a key regulator of CD4 T cell activation. PLoS ONE, 11(8):e0158708. https://doi.org/10.1371/journal.pone.0158708
Li CG, Zhao ZM, Zhou ZP, et al., 2016. Linc-ROR confers gemcitabine resistance to pancreatic cancer cells via inducing autophagy and modulating the miR-124/PTBPl/PKM2 axis. Cancer Chemother Pharmacol, 78(6): 1199–1207. https://doi.org/10.1007/s00280-016-3178-4
Licatalosi DD, Yano M, Fak JJ, et al., 2012. Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes Dev, 26(14): 1626–1642. https://doi.org/10.1101/gad.191338.112
Linares AJ, Lin CH, Damianov A, et al., 2015. The splicing regulator PTBP1 controls the activity of the transcription factor Pbxl during neuronal differentiation. teLife, 4: e09268. https://doi.org/10.7554/eLife.09268
Ling JP, Chhabra R, Merran JD, et al., 2016. PTBP1 and PTBP2 repress nonconserved cryptic exons. Cell Rep, 17(1): 104–113. https://doi.org/10.1016/jxelrep.2016.08.071
Liu C, Yang Z, Wu J, et al., 2018. Long noncoding RNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis. Hepatology, 67(5): 1768–1783. https://doi.org/10.1002/hep.29654
Liu JH, Li YP, Tong JY, et al., 2018. Long non-coding RNA-dependent mechanism to regulate heme biosynthesis and erythrocyte development. Nat Commun, 9(1):4386. https://doi.org/10.1038/s41467-018-06883-x
Llorian M, Schwartz S, Clark TA, et al., 2010. Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nat Struct Mol Biol, 17(9): 1114–1123. https://doi.org/10.1038/nsmb.1881
Llorian M, Gooding C, Bellora N, et al., 2016. The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators. Nucleic Acids Res, 44(18): 8933–8950. https://doi.org/10.1093/nar/gkw560
Lorenzi P, Sangalli A, Fochi S, et al., 2019. RNA-binding proteins RBM20 and PTBP1 regulate the alternative splicing of FHOD3. Int J Biochem Cell Biol, 106:74–83. https://doi.org/10.1016/j.bioce1.2018.11.009
Marzese DM, Liu M, Huynh JL, et al., 2015. Brain metastasis is predetermined in early stages of cutaneous melanoma by CD44v6 expression through epigenetic regulation of the spliceosome. Pigment Cell Melanoma Res, 28(1): 82–93. https://doi.org/10.1111/pcmr.12307
Medina MW, Gao F, Naidoo D, et al., 2011. Coordinately regulated alternative splicing of genes involved in cholesterol biosynthesis and uptake. PLoS ONE, 6(4):e19420. https://doi.org/10.1371/journal.pone.0019420
Méreau A, Anquetil V, Lerivray H, et al., 2015. A posttran-scriptional mechanism that controls Ptbpl abundance in the Xenopus epidermis. Mol Cell Biol, 35(4):758–768. https://doi.org/10.1128/mcb.01040-14
Minami K, Taniguchi K, Sugito N, et al., 2017. MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells. Oncotarget, 8(20):33064–33077. https://doi.org/10.18632/oncotarget.16524
Miyajima M, Zhang BH, Sugiura Y, et al., 2017. Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior. Nat Immunol, 18(12): 1342–1352. https://doi.org/10.1038/ni.3867
Monzón-Casanova E, Screen M, Díaz-Muñoz MD, et al., 2018. The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers. Nat Immunol, 19(3):267–278. https://doi.org/10.1038/s41590-017-0035-5
Noiret M, Méreau A, Angrand G, et al., 2017. Robust identification of Ptbpl-dependent splicing events by a junction-centric approach in Xenopus laevis. Dev Biol, 426(2): 449–459. https://doi.org/10.1016/j.ydbio.2016.08.021
Nordin A, Larsson E, Holmberg M, 2012. The defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1. Hum Mutat, 33(3): 467–470. https://doi.org/10.1002/humu.22002
Oberstrass FC, Auweter SD, Erat M, et al., 2005. Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science, 309(5743):2054–2057. https://doi.org/10.1126/science.1114066
Ouyang GQ, Xiong L, Liu ZP, et al., 2018. Inhibition of autophagy potentiates the apoptosis-inducing effects of photodynamic therapy on human colon cancer cells. Photodiagn Photodyn Ther, 21:396–403. https://doi.org/10.1016/j.pdpdt.2018.01.010
Pospiech N, Cibis H, Dietrich L, et al., 2018. Identification of novel PANDAR protein interaction partners involved in splicing regulation. Sci Rep, 8(1):2798. https://doi.org/10.1038/s41598-018-21105-6
Ramos AD, Andersen RE, Liu SJ, et al., 2015. The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells. Cell Stem Cell, 16(4):439–447. https://doi.org/10.1016/j.stem.2015.02.007
Rawcliffe DFR, Osterman L, Nordin A, et al, 2018. PTBP1 acts as a dominant repressor of the aberrant tissue-specific splicing of ISCU in hereditary myopathy with lactic acidosis. Mol Genet Genomic Med, 6(6): 887–897. https://doi.org/10.1002/mgg3.413
Ren SS, Deng JW, Hong M, et al., 2019. Ethical considerations of cellular immunotherapy for cancer. J Zhejiang Univ-Sci B (Biomed&Biotechnol), 20(1):23–31. https://doi.org/10.1631/jzus.B1800421
Sachdeva M, Zhu SM, Wu FT, et al., 2009. p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA, 106(9):3207–3212. https://doi.org/10.1073/pnas.0808042106
Sang B, Zhang YY, Guo ST, et al, 2018. Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence. Proc Natl Acad Sci USA, 115(50):E11661–E11670. https://doi.org/10.1073/pnas.1805950115
Santiago JA, Potashkin JA, 2015a. Blood biomarkers associated with cognitive decline in early stage and drug-naive Parkinson’s disease patients. PLoS ONE, 10(11):e0142582. https://doi.org/10.1371/journal.pone.0142582
Santiago JA, Potashkin JA, 2015b. Network-based metaanalysis identifies HNF4A and PTBP1 as longitudinally dynamic biomarkers for Parkinson’s disease. Proc Natl Acad Sci USA, 112(7):2257–2262. https://doi.org/10.1073/pnas.1423573112
Sasabe T, Futai E, Ishiura S, 2011. Polypyrimidine tract-binding protein 1 regulates the alternative splicing of dopamine receptor D2. J Neurochem, 116(1): 76–81. https://doi.org/10.1111/j.1471-4159.2010.07086.x
Sasanuma H, Ozawa M, Yoshida N, 2018. RNA-binding protein Ptbpl is essential for BCR-mediated antibody production. Int Immunol, 31(3): 157–166. https://doi.org/10.1093/intimm/dxy077
Sayed ME, Yuan L, Robin JD, et al, 2018. NOVA1 directs PTBP1 to hTERT pre-mRNA and promotes telomerase activity in cancer cells. Oncogene, 38(16):2937–2952. https://doi.org/10.1038/s41388-018-0639-8
Shan H, Hou P, Zhang M, et al., 2018. PTBP1 knockdown in renal cell carcinoma inhibits cell migration, invasion and angiogenesis in vitro and metastasis in vivo via the hypoxia inducible factor-1α pathway. Int J Oncol, 52(5): 1613–1622. https://doi.org/10.3892/ijo.2018.4296
Shan SH, Shi JY, Yang P, et al., 2017. Apigenin restrains colon cancer cell proliferation via targeted blocking of pyruvate kinase M2-dependent glycolysis. J Agric Food Chem, 65(37):8136–8144. https://doi.org/10.1021/acs.jafc.7b02757
Sharma S, Maris C, Allain FHT, et al, 2011. Ul snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression. Mol Cell, 41(5):579–588. https://doi.org/10.1016/j.molcel.2011.02.012
Shi Y, Liu N, Lai WW, et al, 2018. Nuclear EGFR-PKM2 axis induces cancer stem cell-like characteristics in irradiation-resistant cells. Cancer Lett, 422:81–93. https://doi.org/10.1016/jxanlet.2018.02.028
Shinohara H, Kumazaki M, Minami Y, et al., 2016. Perturbation of energy metabolism by fatty-acid derivative AIC-47 and imatinib in BCR-ABL-harboring leukemic cells. Cancer Lett, 371(1):1–11. https://doi.org/10.1016/j.canlet.2015.11.020
Smith P, al Hashimi A, Girard J, et al., 2011. In vivo regulation of amyloid precursor protein neuronal splicing by microRNAs. J Neurochem, 116(2):240–247. https://doi.org/10.1111/j.1471-4159.2010.07097.x
Stork C, Li ZL, Lin L, et al., 2018. Developmental Xist induction is mediated by enhanced splicing. Nucleic Acids Res, 47(3):1532–1543. https://doi.org/10.1093/nar/gkyll98
Sugito N, Taniguchi K, Kuranaga Y, et al., 2017. Cancer-specific energy metabolism in rhabdomyosarcoma cells is regulated by microRNA. Nucleic Acid Ther, 27(6): 365–377. https://doi.org/10.1089/nat.2017.0673
Sugiyama T, Taniguchi K, Matsuhashi N, et al., 2016. MiR-133b inhibits growth of human gastric cancer cells by silencing pyruvate kinase muscle-splicer polypyrimidine tract-binding protein 1. Cancer Sci, 107(12): 1767–1775. https://doi.org/10.1111/cas.13091
Sveen A, Kilpinen S, Ruusulehto A, et al., 2016. Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes. Oncogene, 35(19): 2413–2427. https://doi.org/10.1038/onc.2015.318
Swinburne IA, Meyer CA, Liu XS, et al., 2006. Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription. Genome Res, 16(7):912–921. https://doi.org/10.1101/gr.5211806
Takahashi H, Nishimura J, Kagawa Y, et al., 2015. Significance of polypyrimidine tract-binding protein 1 expression in colorectal cancer. Mol Cancer Ther, 14(7): 1705–1716. https://doi.org/10.1158/1535-7163.mct-14-0142
Takai T, Yoshikawa Y, Inamoto T, et al., 2017. A novel combination RNAi toward Warburg effect by replacement with miR-145 and silencing of PTBP1 induces apoptotic cell death in bladder cancer cells. Int J Mol Sci, 18(1): 179. https://doi.org/10.3390/ijms18010179
Tang SJ, Luo SF, Ho JXJ, et al., 2016. Characterization of the regulation of CD46 RNA alternative splicing. J Biol Chem, 291(27):14311–14323. https://doi.org/10.1074/jbc.M115.710350
Tang ZZ, Sharma S, Zheng S, et al., 2011. Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein. J Biol Chem, 286(12): 10007–10016. https://doi.org/10.1074/jbc.M110.208116
Taniguchi K, Sugito N, Kumazaki M, et al., 2015. Positive feedback of DDX6/c-Myc/PTB1 regulated by miR-124 contributes to maintenance of the Warburg effect in colon cancer cells. Biochim Biophys Acta Mol Basis Dis, 1852(9): 1971–1980. https://doi.org/10.1016/j.bbadis.2015.06.022
Taniguchi K, Sakai M, Sugito N, et al., 2016. PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors. Oncotarget, 7(14): 18940–18952. https://doi.org/10.18632/oncotarget.8005
Taniguchi K, Sugito N, Shinohara H, et al., 2018. Organ-specific microRNAs (MIR122, 137, and 206) contribute to tissue characteristics and carcinogenesis by regulating pyruvate kinase M1/2 (PKM) expression. Int J Mol Sci, 19(5):1276. https://doi.org/10.3390/ijms19051276
Vaquero-Garcia J, Barrera A, Gazzara MR, et al., 2016. A new view of transcriptome complexity and regulation through the lens of local splicing variations. Elife, 5:e11752. https://doi.org/10.7554/eLife.11752
Vuong JK, Lin CH, Zhang M, et al., 2016. PTBP1 and PTBP2 serve both specific and redundant functions in neuronal pre-mRNA splicing. Cell Rep, 17(10):2766–2775. https://doi.org/10.1016/jxelrep.2016.11.034
Wagner EJ, Carstens RP, Garcia-Blanco MA, 1999. A novel isoform ratio switch of the polypyrimidine tract binding protein. Electrophoresis, 20(4-5): 1082–1086.
Wang JL, Yang MY, Xiao S, et al., 2018. Downregulation of castor zinc finger 1 predicts poor prognosis and facilitates hepatocellular carcinoma progression via MAPK/ERK signaling. J Exp Clin Cancer Res, 37(1):45. https://doi.org/10.1186/s13046-018-0720-8
Wang L, Yang LY, Yang ZL, et al., 2019. Glycolytic enzyme PKM2 mediates autophagic activation to promote cell survival in NPM1-mutated leukemia. Int J Biol Sci, 15(4): 882–894. https://doi.org/10.7150/ijbs.30290
Wang ZN, Liu D, Yin B, et al., 2017. High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin. Oncotarget, 8(22): 36185–36202. https://doi.org/10.18632/oncotarget.15873
Wollerton MC, Gooding C, Wagner EJ, et al., 2004. Autoregulation of polypyrimidine tract binding protein by alternative splicing leading to nonsense-mediated decay. Mol Cell, 13(1):91–100. https://doi.org/10.1016/S1097-2765(03)00502-l
Xie R, Chen X, Chen Z, et al., 2019. Polypyrimidine tract binding protein 1 promotes lymphatic metastasis and proliferation of bladder cancer via alternative splicing of MEIS2 and PKM. Cancer Lett, 449:31–44. https://doi.org/10.1016/jxanlet.2019.01.041
Xu J, Liu H, Yang Y, et al., 2019. Genome-wide profiling of cervical RNA-binding proteins identifies human papillomavirus regulation of RNASEH2A expression by viral E7 and E2F1. mBio, 10(1):e02687–18. https://doi.org/10.1128/mBio.02687-18
Xue YC, Zhou Y, Wu TB, et al., 2009. Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol Cell, 36(6):996–1006. https://doi.org/10.1016/j.molcel.2009.12.003
Yang B, Hu PS, Lin XH, et al., 2015. PTBP1 induces ADAR1 p110 isoform expression through IRES-like dependent translation control and influences cell proliferation in gliomas. Cell Mol Life Sci, 72(22):4383–4397. https://doi.org/10.1007/s00018-015-1938-7
Yang Y, Wang CF, Zhao KL, et al., 2018. TRMP, a p53-inducible long noncoding RNA, regulates G1/S cell cycle progression by modulating IRES-dependent p27 translation. Cell Death Dis, 9(9): 886. https://doi.org/10.1038/s41419-018-0884-3
Yao WL, Yue P, Zhang GJ, et al., 2015. Enhancing therapeutic efficacy of the MEK inhibitor, MEK162, by blocking autophagy or inhibiting PI3K/AKT signaling in human lung cancer cells. Cancer Lett, 364(1): 70–78. https://doi.org/10.1016/j.canlet.2015.04.028
Yap K, Lim ZQ, Khandelia P, et al., 2012. Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention. Genes Dev, 26(11):1209–1223. https://doi.org/10.1101/gad.188037.112
Zhang L, Yang Z, Trottier J, et al., 2017. Long noncoding RNA MEG3 induces cholestatic liver injury by interaction with PTBP1 to facilitate shp mRNA decay. Hepatology, 65(2): 604–615. https://doi.org/10.1002/hep.28882
Zhang SL, Wei JS, Li SQ, et al., 2016. MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma. Cancer Lett, 371(2):214–224. https://doi.org/10.1016/j.canlet.2015.11.045
Zhang T, Li JJ, He Y, et al., 2018. A small molecule targeting myoferlin exerts promising anti-tumor effects on breast cancer. Nat Commun, 9(1):3726. https://doi.org/10.1038/s41467-018-06179-0
Zhang XC, Chen MH, Wu XB, et al., 2016. Cell-type-specific alternative splicing governs cell fate in the developing cerebral cortex. Cell, 166(5): 1147–1162.el5. https://doi.org/10.1016/jxell.2016.07.025
Zhao M, Zhuo ML, Zheng X, et al., 2019. FGFRlß is a driver isoform of FGFR1 alternative splicing in breast cancer cells. Oncotarget, 10(1):30–44. https://doi.org/10.18632/oncotarget.26530
Zheng SK, Gray EE, Chawla G, et al., 2012. PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat Neurosci, 15(3):381–388. https://doi.org/10.1038/nn.3026
Zhou C, Wu YL, Chen G, et al., 2011. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol, 12(8):735–742. https://doi.org/10.1016/s1470-2045(11)70184-x
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Cai-ping REN, Wei ZHU, and Bo-lun ZHOU contributed the design of the study. Wei ZHU and Bo-lun ZHOU drafted and critically revised the manuscript. Cai-ping REN, Li-juan RONG, Li YE, Hong-juan XU, Yao ZHOU, Xue-jun YAN, Wei-dong LIU, Bin ZHU, Lei WANG, and Xing-jun JIANG discussed and revised the manuscript. All authors were involved in writing the paper and provided final approval of the submitted and published versions.
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Wei ZHU, Bo-lun ZHOU, Li-juan RONG, Li YE, Hong-juan XU, Yao ZHOU, Xue-jun YAN, Wei-dong LIU, Bin ZHU, Lei WANG, Xing-jun JIANG, and Cai-ping REN declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Project supported by the National Natural Science Foundation of China (Nos. 81773179, 81272972, and 81472355), the Program for New Century Excellent Talents in University (No. NCET-10-0790), the Hunan Provincial Science and Technology Department (Nos. 2016JC 2049 and 2014FJ6006), the Hunan Provincial Natural Science Foundation of China (No. 2016JJ2172), and the Undergraduate Training Programs for Innovation and Entrepreneurship (Nos. 201810533368, GS201910533474, and GS201910533236), China
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Zhu, W., Zhou, Bl., Rong, Lj. et al. Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis. J. Zhejiang Univ. Sci. B 21, 122–136 (2020). https://doi.org/10.1631/jzus.B1900422
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DOI: https://doi.org/10.1631/jzus.B1900422
Key words
- Polypyrimidine tract-binding protein 1 (PTBP1)
- Alternative splicing
- Glycolysis
- M2 isoform of pyruvate kinase (PKM2)
- Cancer