Molecular Mechanisms of Medicinal Plant Securinega suffruticosa-derived Compound Securinine against Spinal Muscular Atrophy based on Network Pharmacology and Experimental Verification


Cite item

Full Text

Abstract

Background:Spinal Muscular Atrophy (SMA) is a severe motor neuronal disorder with high morbidity and mortality. Securinine has shown the potential to treat SMA; however, its anti-SMA role remains unclear.

Objective:This study aims to reveal the anti-SMA mechanisms of securinine.

Methods:Securinine-associated targets were acquired from Herbal Ingredients' Targets (HIT), Similarity Ensemble Approach (SEA), and SuperPred. SMA-associated targets were obtained from GeneCards and Dis- GeNET. Protein-protein interaction (PPI) network was constructed using GeneMANIA, and hug targets were screened using cytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfifiler. Molecular docking was conducted using Pymol and Auto- Dock. In vitro assays were used to verify the anti-SMA effects of securinine.

Results:Twenty-six intersection targets of securinine and SMA were obtained. HDAC1, HDAC2, TOP2A, PIK3R1, PRMT5, JAK2, HSP90AB1, TERT, PTGS2, and PAX8 were the core targets in PPI network. GO analysis demonstrated that the intersecting targets were implicated in the regulation of proteins, steroid hormones, histone deacetylases, and DNA transcription. KEGG analysis, pathway-pathway, and hub target-pathway networks revealed that securinine might treat SMA through TNF, JAK-STAT, Ras, and PI3K-Akt pathways. Securinine had a favorable binding affinity with HDAC1, HSP90AB, JAK2, PRMT5, PTGS2, and TERT. Securinine rescued viability suppression, mitochondria damage, and SMN loss in the SMA cell model. Furthermore, securinine increased HDAC1 and PRMT5 expression, decreased PTGS2 expression, suppressed the JAK2-STAT3 pathway, and promoted the PI3K-Akt pathway.

Conclusion:Securinine might alleviate SMA by elevating HDAC1 and PRMT5 expression and reducing PTGS2 via JAK2-STAT3 suppression and PI3K-Akt activation.

About the authors

Yinhong Zhang

NHC Key Laboratory of Preconception Health Birth in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, Department of Medical Genetics, Yunnan Provincial Clinical Research Center for Birth Defects and Rare Diseases, The First People’s Hospital of Yunnan Province

Email: info@benthamscience.net

Jing He

NHC Key Laboratory of Preconception Health Birth in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, Department of Medical Genetics, Yunnan Provincial Clinical Research Center for Birth Defects and Rare Diseases, The First People’s Hospital of Yunnan Province

Email: info@benthamscience.net

Lifeng Xiang

, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology

Email: info@benthamscience.net

Xinhua Tang

NHC Key Laboratory of Preconception Health Birth in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, Department of Medical Genetics, Yunnan Provincial Clinical Research Center for Birth Defects and Rare Diseases, The First People’s Hospital of Yunnan Province

Email: info@benthamscience.net

Shiyu Wang

School of Medical, Kunming University of Science and Technology

Email: info@benthamscience.net

Aoyu Li

School of Medical, Kunming University of Science and Technology

Email: info@benthamscience.net

Chaoyan Wang

School of Medical, Kunming University of Science and Technology

Email: info@benthamscience.net

Li Li

, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technolog

Author for correspondence.
Email: info@benthamscience.net

Baosheng Zhu

NHC Key Laboratory of Preconception Health Birth in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, Department of Medical Genetics, Yunnan Provincial Clinical Research Center for Birth Defects and Rare Diseases, The First People’s Hospital of Yunnan Province

Author for correspondence.
Email: info@benthamscience.net

References

  1. Ross LF, Kwon JM. Spinal muscular atrophy: Past, present, and future. Neoreviews 2019; 20(8): e437-51. doi: 10.1542/neo.20-8-e437 PMID: 31371553
  2. Mercuri E, Sumner CJ, Muntoni F, Darras BT, Finkel RS. Spinal muscular atrophy. Nat Rev Dis Primers 2022; 8(1): 52. doi: 10.1038/s41572-022-00380-8 PMID: 35927425
  3. Butterfield RJ. Spinal muscular atrophy treatments, newborn screening, and the creation of a neurogenetics urgency. Semin Pediatr Neurol 2021; 38: 100899. doi: 10.1016/j.spen.2021.100899 PMID: 34183144
  4. Bozorg Qomi S, Asghari A, Salmaninejad A, Mojarrad M. Spinal muscular atrophy and common therapeutic advances. Fetal Pediatr Pathol 2019; 38(3): 226-38. doi: 10.1080/15513815.2018.1520374 PMID: 31060440
  5. Aslesh T, Yokota T. Restoring SMN expression: An overview of the therapeutic developments for the treatment of spinal muscular atrophy. Cells 2022; 11(3): 417. doi: 10.3390/cells11030417 PMID: 35159227
  6. James R, Chaytow H, Ledahawsky LM, Gillingwater TH. Revisiting the role of mitochondria in spinal muscular atrophy. Cell Mol Life Sci 2021; 78(10): 4785-804. doi: 10.1007/s00018-021-03819-5 PMID: 33821292
  7. Gidaro T, Servais L. Nusinersen treatment of spinal muscular atrophy: Current knowledge and existing gaps. Dev Med Child Neurol 2019; 61(1): 19-24. doi: 10.1111/dmcn.14027 PMID: 30221755
  8. Hoy SM. Onasemnogene abeparvovec: First global approval. Drugs 2019; 79(11): 1255-62. doi: 10.1007/s40265-019-01162-5 PMID: 31270752
  9. Cleary Y, Gertz M, Grimsey P, et al. Model-based drug–drug interaction extrapolation strategy from adults to children: Risdiplam in pediatric patients with spinal muscular atrophy. Clin Pharmacol Ther 2021; 110(6): 1547-57. doi: 10.1002/cpt.2384 PMID: 34347881
  10. Kang P, Wu Z, Zhong Y, et al. A network pharmacology and molecular docking strategy to explore potential targets and mechanisms underlying the effect of curcumin on osteonecrosis of the femoral head in systemic lupus erythematosus. BioMed Res Int 2021; 2021: 1-14. doi: 10.1155/2021/5538643 PMID: 34557547
  11. Ullah R, Alqahtani AS. GC-MS Analysis, heavy metals, biological, and toxicological evaluation of Reseda muricata and Marrubium vulgare methanol extracts. Evid Based Complement Alternat Med 2022; 2022: 1-9. doi: 10.1155/2022/2284328 PMID: 35356243
  12. Leonoudakis D, Rane A, Angeli S, Lithgow GJ, Andersen JK, Chinta SJ. Anti-inflammatory and neuroprotective role of natural product securinine in activated glial cells: Implications for Parkinson’s disease. Mediators Inflamm 2017; 2017: 1-11. doi: 10.1155/2017/8302636 PMID: 28473732
  13. Zhang D, Liu H, Yang B, Hu J, Cheng Y. L-securinine inhibits cell growth and metastasis of human androgen-independent prostate cancer DU145 cells via regulating mitochondrial and AGTR1/MEK/ERK/STAT3/PAX2 apoptotic pathways. Biosci Rep 2019; 39(5): BSR20190469. doi: 10.1042/BSR20190469 PMID: 30975734
  14. Wu ZL, Huang XJ, Xu MT, et al. Flueggeacosines A–C, dimeric securinine-type alkaloid analogues with neuronal differentiation activity from Flueggea suffruticosa. Org Lett 2018; 20(23): 7703-7. doi: 10.1021/acs.orglett.8b03432 PMID: 30484660
  15. Chen YC, Chang JG, Liu TY, Jong YJ, Cheng WL, Yuo CY. Securinine enhances SMN2 exon 7 inclusion in spinal muscular atrophy cells. Biomed Pharmacother 2017; 88: 708-14. doi: 10.1016/j.biopha.2017.01.104 PMID: 28152480
  16. Yuan H, Ma Q, Cui H, et al. How can synergism of traditional medicines benefit from network pharmacology? Molecules 2017; 22(7): 1135. doi: 10.3390/molecules22071135 PMID: 28686181
  17. Xu S, Wang L, Pan X. An evaluation of combined strategies for improving the performance of molecular docking. J Bioinform Comput Biol 2021; 19(2): 2150003. doi: 10.1142/S0219720021500037 PMID: 33641636
  18. Yan D, Zheng G, Wang C, et al. HIT 2.0: An enhanced platform for herbal ingredients’. Nucleic Acids Res 2022; 50(D1): D1238-43. doi: 10.1093/nar/gkab1011 PMID: 34986599
  19. Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotechnol 2007; 25(2): 197-206. doi: 10.1038/nbt1284 PMID: 17287757
  20. Gallo K, Goede A, Preissner R, Gohlke BO. SuperPred 3.0: Drug classification and target prediction-a machine learning approach. Nucleic Acids Res 2022; 50(W1): W726-31. doi: 10.1093/nar/gkac297 PMID: 35524552
  21. Bateman A, Martin M-J, Orchard S, et al. UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res 2021; 49(D1): D480-9. doi: 10.1093/nar/gkaa1100 PMID: 33237286
  22. Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: The human gene integrator. Database (Oxford) 2010; 2010(0): baq020. doi: 10.1093/database/baq020 PMID: 20689021
  23. Piñero J, Ramírez-Anguita JM, Saüch-Pitarch J, et al. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res 2020; 48(D1): D845-55. PMID: 31680165
  24. Franz M, Rodriguez H, Lopes C, et al. GeneMANIA update 2018. Nucleic Acids Res 2018; 46(W1): W60-4. doi: 10.1093/nar/gky311 PMID: 29912392
  25. Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014; 8(S4) (Suppl. 4): S11. doi: 10.1186/1752-0509-8-S4-S11 PMID: 25521941
  26. Chen L, Zhang YH, Wang S, Zhang Y, Huang T, Cai YD. Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways. PLoS One 2017; 12(9): e0184129. doi: 10.1371/journal.pone.0184129 PMID: 28873455
  27. Yang M, Chen J, Xu L, et al. A network pharmacology approach to uncover the molecular mechanisms of herbal formula Ban-Xia-Xie-Xin-Tang. Evid Based Complement Alternat Med 2018; 2018: 1-22. doi: 10.1155/2018/4050714 PMID: 30410554
  28. Nicolau S, Waldrop MA, Connolly AM, Mendell JR. Spinal muscular atrophy. Semin Pediatr Neurol 2021; 37: 100878. doi: 10.1016/j.spen.2021.100878 PMID: 33892848
  29. Barkats M. SMA: From gene discovery to gene therapy. Med Sci (Paris) 2020; 36(2): 137-40. doi: 10.1051/medsci/2020010 PMID: 32129749
  30. Kwak SC, Jeong DH, Cheon YH, et al. Securinine suppresses osteoclastogenesis and ameliorates inflammatory bone loss. Phytother Res 2020; 34(11): 3029-40. doi: 10.1002/ptr.6735 PMID: 32510717
  31. Klochkov S, Neganova M. Unique indolizidine alkaloid securinine is a promising scaffold for the development of neuroprotective and antitumor drugs. RSC Adv 2021; 11(31): 19185-95. doi: 10.1039/D1RA02558A PMID: 35478659
  32. Liu CJ, Fan XD, Jiang JG, Chen QX, Zhu W. Potential anticancer activities of securinine and its molecular targets. Phytomedicine 2022; 106: 154417. doi: 10.1016/j.phymed.2022.154417 PMID: 36063584
  33. Xiao H, Zhang Q, Zhong P, et al. Securinine promotes neuronal development and exhibits antidepressant-like effects via mtor activation. ACS Chem Neurosci 2021; 12(19): 3650-61. doi: 10.1021/acschemneuro.1c00381 PMID: 34541857
  34. Hou W, Huang H, Wu XQ, Lan JX. Bioactivities and mechanism of action of securinega alkaloids derivatives reported prior to 2022. Biomed Pharmacother 2023; 158: 114190. doi: 10.1016/j.biopha.2022.114190 PMID: 36916441
  35. Beutler JA, Karbon EW, Brubaker AN, Malik R, Curtis DR, Enna SJ. Securinine alkaloids: A new class of GABA receptor antagonist. Brain Res 1985; 330(1): 135-40. doi: 10.1016/0006-8993(85)90014-9 PMID: 2985189
  36. Shipman M, Lubick K, Fouchard D, et al. Proteomic and systems biology analysis of monocytes exposed to securinine, a GABA(A) receptor antagonist and immune adjuvant. PLoS One 2012; 7(9): e41278. doi: 10.1371/journal.pone.0041278 PMID: 23028424
  37. Abdelkader HA, Amin I, Rashed LA, Samir M, Ezzat M. Histone deacetylase 1 in patients with Alopecia areata and Acne vulgaris: An epigenetic alteration. Australas J Dermatol 2022; 63(2): e138-41. doi: 10.1111/ajd.13784 PMID: 35076083
  38. Smalley JP, Baker IM, Pytel WA, et al. Optimization of class I histone deacetylase PROTACs reveals that HDAC1/2 degradation is critical to induce apoptosis and cell arrest in cancer cells. J Med Chem 2022; 65(7): 5642-59. doi: 10.1021/acs.jmedchem.1c02179 PMID: 35293758
  39. Pagliarini V, Guerra M, Di Rosa V, Compagnucci C, Sette C. Combined treatment with the histone deacetylase inhibitor LBH589 and a splice-switch antisense oligonucleotide enhances SMN2 splicing and SMN expression in spinal muscular atrophy cells. J Neurochem 2020; 153(2): 264-75. doi: 10.1111/jnc.14935 PMID: 31811660
  40. Liimatainen K, Huttunen R, Latonen L, Ruusuvuori P. Convolutional neural network-based artificial intelligence for classification of protein localization patterns. Biomolecules 2021; 11(2): 264. doi: 10.3390/biom11020264 PMID: 33670112
  41. Wu S, Li YL, Cheng NY, et al. c.835-5T>G Variant in SMN1 gene causes transcript exclusion of Exon 7 and Spinal muscular atrophy. J Mol Neurosci 2018; 65(2): 196-202. doi: 10.1007/s12031-018-1079-1 PMID: 29799103
  42. Day JW, Howell K, Place A, et al. Advances and limitations for the treatment of spinal muscular atrophy. BMC Pediatr 2022; 22(1): 632. doi: 10.1186/s12887-022-03671-x PMID: 36329412
  43. Reilly A, Chehade L, Kothary R. Curing SMA: Are we there yet? Gene Ther 2023; 30(1-2): 8-17. doi: 10.1038/s41434-022-00349-y PMID: 35614235
  44. Janzen E, Mendoza-Ferreira N, Hosseinibarkooie S, et al. CHP1 reduction ameliorates spinal muscular atrophy pathology by restoring calcineurin activity and endocytosis. Brain 2018; 141(8): 2343-61. doi: 10.1093/brain/awy167 PMID: 29961886
  45. Berciano MT, Castillo-Iglesias MS, Val-Bernal JF, et al. Mislocalization of SMN from the I-band and M-band in human skeletal myofibers in spinal muscular atrophy associates with primary structural alterations of the sarcomere. Cell Tissue Res 2020; 381(3): 461-78. doi: 10.1007/s00441-020-03236-3 PMID: 32676861
  46. McLeod VM, Chiam MDF, Lau CL, Rupasinghe TW, Boon WC, Turner BJ. Dysregulation of steroid hormone receptors in motor neurons and glia associates with disease progression in ALS Mice. Endocrinology 2020; 161(9): bqaa113. doi: 10.1210/endocr/bqaa113 PMID: 32621747
  47. Wan B, Feng P, Guan Z, Sheng L, Liu Z, Hua Y. A severe mouse model of spinal muscular atrophy develops early systemic inflammation. Hum Mol Genet 2018; 27(23): 4061-76. doi: 10.1093/hmg/ddy300 PMID: 30137324
  48. Thomas EA, D’Mello SR. Complex neuroprotective and neurotoxic effects of histone deacetylases. J Neurochem 2018; 145(2): 96-110. doi: 10.1111/jnc.14309 PMID: 29355955
  49. Lai JI, Leman LJ, Ku S, et al. Cyclic tetrapeptide HDAC inhibitors as potential therapeutics for spinal muscular atrophy: Screening with iPSC-derived neuronal cells. Bioorg Med Chem Lett 2017; 27(15): 3289-93. doi: 10.1016/j.bmcl.2017.06.027 PMID: 28648462
  50. Raffaele S, Lombardi M, Verderio C, Fumagalli M. TNF production and release from microglia via extracellular vesicles: Impact on brain functions. Cells 2020; 9(10): 2145. doi: 10.3390/cells9102145 PMID: 32977412
  51. Hanna A, Frangogiannis NG. Inflammatory cytokines and chemokines as therapeutic targets in heart failure. Cardiovasc Drugs Ther 2020; 34(6): 849-63. doi: 10.1007/s10557-020-07071-0 PMID: 32902739
  52. Ando S, Osanai D, Takahashi K, Nakamura S, Shimazawa M, Hara H. Survival motor neuron protein regulates oxidative stress and inflammatory response in microglia of the spinal cord in spinal muscular atrophy. J Pharmacol Sci 2020; 144(4): 204-11. doi: 10.1016/j.jphs.2020.09.001 PMID: 33070839
  53. Yin Q, Wang L, Yu H, Chen D, Zhu W, Sun C. Pharmacological effects of polyphenol phytochemicals on the JAK-STAT signaling pathway. Front Pharmacol 2021; 12: 716672. doi: 10.3389/fphar.2021.716672 PMID: 34539403
  54. Yan Z, Gibson SA, Buckley JA, Qin H, Benveniste EN. Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases. Clin Immunol 2018; 189: 4-13. doi: 10.1016/j.clim.2016.09.014 PMID: 27713030
  55. Dai J, Xu LJ, Han GD, et al. MicroRNA-125b promotes the regeneration and repair of spinal cord injury through regulation of JAK/STAT pathway. Eur Rev Med Pharmacol Sci 2018; 22(3): 582-9. PMID: 29461585
  56. Yoshino H, Yin G, Kawaguchi R, et al. Identification of lysine methylation in the core GTPase domain by GoMADScan. PLoS One 2019; 14(8): e0219436. doi: 10.1371/journal.pone.0219436 PMID: 31390367
  57. Pompura SL, Dominguez-Villar M. The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and function. J Leukoc Biol 2018; 103(6): 1065-76. doi: 10.1002/JLB.2MIR0817-349R PMID: 29357116
  58. Sansa A, de la Fuente S, Comella JX, Garcera A, Soler RM. Intracellular pathways involved in cell survival are deregulated in mouse and human spinal muscular atrophy motoneurons. Neurobiol Dis 2021; 155: 105366. doi: 10.1016/j.nbd.2021.105366 PMID: 33845129
  59. Chen JS, Wang HK, Hsu CY, et al. HDAC1 deregulation promotes neuronal loss and deficit of motor function in stroke pathogenesis. Sci Rep 2021; 11(1): 16354. doi: 10.1038/s41598-021-95837-3 PMID: 34381129
  60. Kumar V, Kundu S, Singh A, Singh S. Understanding the role of histone deacetylase and their inhibitors in neurodegenerative disorders: Current targets and future perspective. Curr Neuropharmacol 2022; 20(1): 158-78. doi: 10.2174/1570159X19666210609160017 PMID: 34151764
  61. Tao CC, Hsu WL, Ma YL, Cheng SJ, Lee EHY. Epigenetic regulation of HDAC1 SUMOylation as an endogenous neuroprotection against Aβ toxicity in a mouse model of Alzheimer’s disease. Cell Death Differ 2017; 24(4): 597-614. doi: 10.1038/cdd.2016.161 PMID: 28186506
  62. Zhang H, Yin X, Zhang X, et al. HSP90AB1 promotes the proliferation, migration, and glycolysis of head and neck squamous cell carcinoma. Technol Cancer Res Treat 2022; 21 doi: 10.1177/15330338221118202 PMID: 35929142
  63. Siebert A, Gattringer V, Weishaupt JH, Behrends C. ALS-linked loss of Cyclin-F function affects HSP90. Life Sci Alliance 2022; 5(12): e202101359. doi: 10.26508/lsa.202101359 PMID: 36114006
  64. Gonzalez-Rodriguez M, Villar-Conde S, Astillero-Lopez V, et al. Neurodegeneration and astrogliosis in the human CA1 hippocampal subfield are related to hsp90ab1 and bag3 in Alzheimer’s disease. Int J Mol Sci 2021; 23(1): 165. doi: 10.3390/ijms23010165 PMID: 35008592
  65. Zhu H, Jian Z, Zhong Y, et al. Janus kinase inhibition ameliorates ischemic stroke injury and neuroinflammation through reducing NLRP3 inflammasome activation via JAK2/STAT3 pathway inhibition. Front Immunol 2021; 12: 714943. doi: 10.3389/fimmu.2021.714943 PMID: 34367186
  66. Xu M, Ni H, Xu L, et al. B14 ameliorates bone cancer pain through downregulating spinal interleukin-1β via suppressing neuron JAK2/STAT3 pathway. Mol Pain 2019; 15 doi: 10.1177/1744806919886498 PMID: 31615322
  67. Xiong J, Zhou H, Lu D, et al. Levetiracetam Reduces early inflammatory response after experimental intracerebral hemorrhage by regulating the Janus Kinase 2 (JAK2)–Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway. Med Sci Monit 2020; 26: e922741. doi: 10.12659/MSM.922741 PMID: 32289810
  68. Yang H, Wang H, Shu Y, Li X. miR-103 promotes neurite outgrowth and suppresses cells apoptosis by targeting prostaglandin-endoperoxide synthase 2 in cellular models of Alzheimer’s disease. Front Cell Neurosci 2018; 12: 91. doi: 10.3389/fncel.2018.00091 PMID: 29674956
  69. Zhuang J, Chen Z, Cai P, et al. Targeting MicroRNA-125b Promotes neurite outgrowth but represses cell apoptosis and inflammation via blocking PTGS2 and CDK5 in a FOXQ1-dependent way in Alzheimer disease. Front Cell Neurosci 2020; 14: 587747. doi: 10.3389/fncel.2020.587747 PMID: 33408612
  70. Chen Y, Shao X, Zhao X, et al. Targeting protein arginine methyltransferase 5 in cancers: Roles, inhibitors and mechanisms. Biomed Pharmacother 2021; 144: 112252. doi: 10.1016/j.biopha.2021.112252 PMID: 34619493
  71. Yuan Y, Nie H. Protein arginine methyltransferase 5: A potential cancer therapeutic target. Cell Oncol (Dordr) 2021; 44(1): 33-44. doi: 10.1007/s13402-020-00577-7 PMID: 33469838
  72. Lanfranco M, Vassallo N, Cauchi RJ. Spinal muscular atrophy: From defective chaperoning of snRNP assembly to neuromuscular dysfunction. Front Mol Biosci 2017; 4: 41. doi: 10.3389/fmolb.2017.00041 PMID: 28642865
  73. Shim HS, Horner JW, Wu CJ, et al. Telomerase reverse transcriptase preserves neuron survival and cognition in Alzheimer’s disease models. Nature Aging 2021; 1(12): 1162-74. doi: 10.1038/s43587-021-00146-z PMID: 35036927
  74. McKelvey BA, Umbricht CB, Zeiger MA. Telomerase Reverse Transcriptase (TERT) regulation in thyroid cancer: A review. Front Endocrinol (Lausanne) 2020; 11: 485. doi: 10.3389/fendo.2020.00485 PMID: 32849278
  75. Zou Y, Cong Y, Zhou J. Implications of telomerase reverse transcriptase in tumor metastasis. BMB Rep 2020; 53(9): 458-65. doi: 10.5483/BMBRep.2020.53.9.108 PMID: 32731912
  76. Singh RN, Howell MD, Ottesen EW, Singh NN. Diverse role of survival motor neuron protein. Biochim Biophys Acta Gene Regul Mech 2017; 1860(3): 299-315. doi: 10.1016/j.bbagrm.2016.12.008 PMID: 28095296

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers