探討bFGF與癌症惡病質信號對MRFs的調控機制

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：69

、訪客IP：3.16.130.170

姓名

黃凱帆(Kai-Fan Huang) 查詢紙本館藏

畢業系所

生命科學系

論文名稱

探討bFGF與癌症惡病質信號對MRFs的調控機制
(The transcriptional regulation of MRFs by bFGF and cancer cachexia signals)

相關論文

★ Thirst control of water-seeking behavior in Drosophila	★ KLHL17在癲癇與自閉症中之角色
★ MyoD對於PGC-1α 基因表現之調控機制	★ 雄性素受體對於肌肉前驅細胞決定的功用
★ Nanog和Oct4表現對肌肉分化之影響	★ 大量表現幹細胞專有轉錄因子抑制肌肉細胞走向分化
★ FOXOs 轉錄調控因子家族對肌肉細胞末期分化的影響	★ 大量表現 Oct4 與 Nanog 抑制肌纖維母細胞 C2C12 分化
★ 在終極肌肉分化時，肌肉性bHLH轉錄因子對PGC-1α的調控	★ FoxOs 大量表現對肌肉細胞末期分化的影響
★ 觀察肌肉生成轉錄因子如何調控Ｍ- 和Ｎ- cadherin 表現	★ Oc4和Nanog共同抑制末端肌肉分化
★ FoxO6在肌原母細胞中的代謝及分化中所扮演的角色	★ PGC-1α 與 Stra13 間之交互作用
★ 探討大量表現 FoxO6 對肌肉終極分化的影響以及尋找 FoxO6 蛋白質在 PGC-1 alpha 啟動子上的結合位	★ 探討丙戊酸 (Valporic acid) 於肌肉細胞中活化 Oct4 promoter 的機制

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

至系統瀏覽論文 (2026-7-31以後開放)

摘要(中)

MRFs包含了Myf5、MyoD、Myogenin和MRF4，它們負責決定肌肉細胞命運及分化，因此對於骨骼肌生成扮演著重要的角色。而鹼性纖維母細胞生長因子(bFGF)常被用來培養肌肉幹細胞，但同時也會抑制肌肉生成及MyoD的表現，反之，會活化Myf5的表現。此外，有一種常在癌症末期病人中出現的併發症稱為癌症惡病質，會抑制肌肉生成及誘導肌肉萎縮，同時也會抑制MyoD的表現。此篇研究想探討鹼性纖維母細胞生長因子和癌症惡病質訊號是如何調控MRFs的表現。首先，實驗結果證實GST-bFGF重組蛋白以及C26癌細胞的條件培養基可以成功模擬bFGF和癌症惡病質訊號。接著，實驗結果發現，bFGF和癌症惡病質訊號會增加MyoD的RNA穩定度。我們也找出了許多位於MyoD啟動子上游且會被bFGF和癌症惡病質信號調控的順式因子(cis-elemts)。先前研究發現，MyoD有一段增強子可以轉錄出一段不會被轉譯成蛋白質的RNA，它可以幫助MyoD的表現，因此我們發現bFGF信號會抑制此段RNA的轉錄，然而，大量表現此段RNA沒辦法挽救被bFGF信號抑制的MyoD表現。因此，詳細的調控機制還需要再進一步研究。此外，我們發現Myf5啟動子會被bFGF和癌症惡病質信號抑制，這與Myf5的RNA表現是相反的結果，詳細的調控機制還需要更進一步的研究。

摘要(英)

Myogenic regulatory factors (MRFs), including Myf5, MyoD, Myogenin and MRF4, are essential for skeletal muscle (SKM) lineage determination and differentiation. Basic Fibroblast Growth Factor (bFGF) is commonly used for culturing myogenic stem cells (MuSC, or satellite cells) but is known to activate Myf5 while inhibiting MyoD expression. In terminal-stage cancers, serious SKM wasting (cachexia) occurs, and MyoD expression is similarly repressed while Myf5 expression is upregulated by cachexia signals. Our lab has confirmed that recombinant GST-bFGF and C26 cell-conditioned medium (C26M) inhibit both myogenesis and MyoD expression in C2C12 cells. However, this inhibition is less pronounced in satellite cells as compared to C2C12 cells, necessitating further investigation into the reasons for this difference. Also, MyoD mRNA stability is increased by bFGF in both growth medium (GM) and differentiation medium (DM), as well as by cachexia signals, suggesting a complex regulatory mechanism affecting MyoD expression at multiple levels. Moreover, various MyoD cis-elements have been identified as targets of bFGF signaling at different myogenic stages. Multiple MyoD cis-elements are also targeted by C26M. Additionally, the Myf5 promoter is repressed by bFGF and C26M signals, which presents a discrepancy between promoter activity and mRNA level that needs further investigation. Furthermore, CREeRNA, a non-coding RNA transcribed from CRE and critical for MyoD epigenetic activation, is repressed by bFGF. However, overexpression of CREeRNA does not rescue the bFGF-repressed MyoD mRNA expression in GM. Additionally, Myf5 promoter activity is repressed by bFGF and C26M, which is opposite to the transcriptional expression. Thus, the mechanism needs to be further investigated. Currently, efforts are focused on identifying the transcription factors mediating the repressive effects of bFGF and C26M on MyoD expression. Understanding these mechanisms will provide deeper insights into the regulation of MyoD and potential therapeutic strategies for muscle-wasting conditions associated with cancer cachexia.

關鍵字(中)

★ 肌肉生成
★ 癌症惡病質
★ 鹼性纖維母細胞生長因子

關鍵字(英)

★ bFGF
★ cancer cachexia
★ myogenesis
★ MRFs

論文目次

摘要 i
Abstract ii
Graphical Abstract iv
Declaration v
Acknowledgment vi
Table of contents vii
List of Figures xi
I. Introduction 1
I-1、 Myogenesis 1
I-1-1. Postnatal skeletal muscle differentiation 1
I-1-2. Myogenic regulatory factors (MRFs) 2
I-1-2-2. MyoD 3
I-1-2-3. Myf5 and MRF4 4
I-2、 Basic fibroblast growth factor 5
I-2-1. bFGF and FGFR expression in satellite cells and skeletal muscle regeneration 5
I-2-2. Role of bFGF in muscle and skeleton development 6
I-3、 Cancer cachexia 7
I-3-1. Definition of cancer cachexia 7
I-3-2. Signaling involved in skeletal muscle wasting 7
I-3-3. Pro-inflammatory factors in cancer cachexia 8
I-3-4. The revealed regulation of MyoD expression in cancer cachexia 9
I-4、 Aims 10
II. Materials and methods 12
II-1、 List of cloning strategies of various plasmids 12
II-2、 Site-directed mutagenesis by overlapping PCR 17
II-3、 Cell culture 17
II-3-1. Cell line 18
II-3-2. Stable clone 18
II-3-3. Satellite cell 19
II-3-4. Transient transfection 19
II-4、 Luciferase assay 19
II-5、 mRNA stability assay 20
II-6、 Immunoflueoresense 22
II-7、 Purification of recombinant protein 22
II-8、 Western blot 24
II-9、 Statistical Analysis 25
III. Results 26
III-1、 GST-bFGF is purified successfully. 26
III-2、 Our homemade GST-bFGF has the same effect as commercial bFGF to C2C12. 26
III-3、 bFGF and cancer cachexia signals inhibit myogenesis and myogenic-related gene expression. 27
III-4、 The effect of GST-bFGF on various signaling pathways at different myogenic stages. 28
III-5、 GST-bFGF and C26M repress MyoD transcriptional level without decreasing mRNA stability 29
III-6、 bFGF and cancer cachexia signals repress MyoD expression by targeting different cis-elements. 30
III-7、 GST-bFGF represses MyoD transcriptional level expression in GM not by inhibiting CREeRNA expression instead of MyoD transactivational activity. 31
III-8、 The effects of C26M on the overexpression of MyoD and its downstream genes were examined. 33
III-9、 The effect of bFGF and cancer cachexia signals on Myf5 and MRF4 promoters. 34
III-10、 The effects of bFGF and cancer cachexia signals on the different promoters 35
IV. Discussion 37
IV-1、 Differential effects of C26M on myogenesis and myogenic-related genes in C2C12 cells and satellite cells 37
IV-2、 The effect of GST-bFGF on the signaling pathways. 38
IV-3、 The effect of bFGF and C26M on MyoD mRNA stability 38
IV-4、 The cis-elements of MyoD targeted by bFGF and cancer cachexia signals 39
IV-5、 The effects of bFGF and cancer cachexia signals on Myf5 and MRF4 promoters. 40
V. Figures 42
VI. Reference 62
VII. Appendixes 69
VII-1、 Cloning strategies 69
VII-1-1. Restriction enzyme digestion 69
VII-1-2. Polymerase 69
VII-1-3. Klenow 69
VII-1-4. PNK (T4 Polynucleotide Kinase) 70
VII-1-5. Quick CIP (calf intestinal alkaline phosphatase) 70
VII-1-6. T4 DNA Ligase 70
VII-2、 Solutions 71
VII-3、 Primer lists 72

參考文獻

1. Soleimani, V.D., et al., Transcriptional dominance of Pax7 in adult myogenesis is due to high-affinity recognition of homeodomain motifs. Dev Cell, 2012. 22(6): p. 1208-20.
2. Comai, G. and S. Tajbakhsh, Molecular and cellular regulation of skeletal myogenesis. Curr Top Dev Biol, 2014. 110: p. 1-73.
3. Dumont, N.A., Y.X. Wang, and M.A. Rudnicki, Intrinsic and extrinsic mechanisms regulating satellite cell function. Development, 2015. 142(9): p. 1572-81.
4. Dumont, N.A., et al., Satellite Cells and Skeletal Muscle Regeneration. Compr Physiol, 2015. 5(3): p. 1027-59.
5. Crist, C.G., D. Montarras, and M. Buckingham, Muscle satellite cells are primed for myogenesis but maintain quiescence with sequestration of Myf5 mRNA targeted by microRNA-31 in mRNP granules. Cell Stem Cell, 2012. 11(1): p. 118-26.
6. Grifone, R., et al., Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo. Development, 2005. 132(9): p. 2235-49.
7. Hu, P., et al., Codependent activators direct myoblast-specific MyoD transcription. Dev Cell, 2008. 15(4): p. 534-46.
8. Deato, M.D., et al., MyoD targets TAF3/TRF3 to activate myogenin transcription. Mol Cell, 2008. 32(1): p. 96-105.
9. Liu, Q.C., et al., Comparative expression profiling identifies differential roles for Myogenin and p38alpha MAPK signaling in myogenesis. J Mol Cell Biol, 2012. 4(6): p. 386-97.
10. Hinterberger, T.J., et al., Expression of the muscle regulatory factor MRF4 during somite and skeletal myofiber development. Dev Biol, 1991. 147(1): p. 144-56.
11. Hernandez-Hernandez, J.M., et al., The myogenic regulatory factors, determinants of muscle development, cell identity and regeneration. Semin Cell Dev Biol, 2017. 72: p. 10-18.
12. Singh, K. and F.J. Dilworth, Differential modulation of cell cycle progression distinguishes members of the myogenic regulatory factor family of transcription factors. FEBS J, 2013. 280(17): p. 3991-4003.
13. Rudnicki, M.A., et al., Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell, 1992. 71(3): p. 383-90.
14. Rudnicki, M.A., et al., MyoD or Myf-5 is required for the formation of skeletal muscle. Cell, 1993. 75(7): p. 1351-9.
15. Rudnicki, M.A. and R. Jaenisch, The MyoD family of transcription factors and skeletal myogenesis. Bioessays, 1995. 17(3): p. 203-9.
16. Hasty, P., et al., Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature, 1993. 364(6437): p. 501-6.
17. Moretti, I., et al., MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity. Nat Commun, 2016. 7: p. 12397.
18. Davis, R.L., H. Weintraub, and A.B. Lassar, Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell, 1987. 51(6): p. 987-1000.
19. Asakura, A., G.E. Lyons, and S.J. Tapscott, The regulation of MyoD gene expression: conserved elements mediate expression in embryonic axial muscle. Dev Biol, 1995. 171(2): p. 386-98.
20. Chen, J.C., C.M. Love, and D.J. Goldhamer, Two upstream enhancers collaborate to regulate the spatial patterning and timing of MyoD transcription during mouse development. Dev Dyn, 2001. 221(3): p. 274-88.
21. Chen, J.C., R. Ramachandran, and D.J. Goldhamer, Essential and redundant functions of the MyoD distal regulatory region revealed by targeted mutagenesis. Dev Biol, 2002. 245(1): p. 213-23.
22. Faerman, A., et al., The distal human myoD enhancer sequences direct unique muscle-specific patterns of lacZ expression during mouse development. Dev Biol, 1995. 171(1): p. 27-38.
23. Goldhamer, D.J., et al., Regulatory elements that control the lineage-specific expression of myoD. Science, 1992. 256(5056): p. 538-42.
24. Goldhamer, D.J., et al., Embryonic activation of the myoD gene is regulated by a highly conserved distal control element. Development, 1995. 121(3): p. 637-49.
25. L′Honore, A., et al., MyoD distal regulatory region contains an SRF binding CArG element required for MyoD expression in skeletal myoblasts and during muscle regeneration. Mol Biol Cell, 2003. 14(5): p. 2151-62.
26. Tapscott, S.J., A.B. Lassar, and H. Weintraub, A novel myoblast enhancer element mediates MyoD transcription. Mol Cell Biol, 1992. 12(11): p. 4994-5003.
27. Chen, J.C. and D.J. Goldhamer, The core enhancer is essential for proper timing of MyoD activation in limb buds and branchial arches. Dev Biol, 2004. 265(2): p. 502-12.
28. Hughes, S.M., et al., Selective accumulation of MyoD and myogenin mRNAs in fast and slow adult skeletal muscle is controlled by innervation and hormones. Development, 1993. 118(4): p. 1137-47.
29. Kablar, B., et al., MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle. Development, 1997. 124(23): p. 4729-38.
30. Fomin, M., N. Nomokonova, and H.H. Arnold, Identification of a critical control element directing expression of the muscle-specific transcription factor MRF4 in the mouse embryo. Dev Biol, 2004. 272(2): p. 498-509.
31. Summerbell, D., et al., The expression of Myf5 in the developing mouse embryo is controlled by discrete and dispersed enhancers specific for particular populations of skeletal muscle precursors. Development, 2000. 127(17): p. 3745-57.
32. Chen, Y.H., et al., Multiple upstream modules regulate zebrafish myf5 expression. BMC Dev Biol, 2007. 7: p. 1.
33. Pawlikowski, B., et al., Regulation of skeletal muscle stem cells by fibroblast growth factors. Dev Dyn, 2017. 246(5): p. 359-367.
34. Belov, A.A. and M. Mohammadi, Molecular mechanisms of fibroblast growth factor signaling in physiology and pathology. Cold Spring Harb Perspect Biol, 2013. 5(6).
35. Yin, H., F. Price, and M.A. Rudnicki, Satellite cells and the muscle stem cell niche. Physiol Rev, 2013. 93(1): p. 23-67.
36. Webster, M.T., et al., Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding Myogenic Progenitors during Regeneration. Cell Stem Cell, 2016. 18(2): p. 243-52.
37. Anderson, J.E., et al., The time course of basic fibroblast growth factor expression in crush-injured skeletal muscles of SJL/J and BALB/c mice. Exp Cell Res, 1995. 216(2): p. 325-34.
38. Chakkalakal, J.V., et al., The aged niche disrupts muscle stem cell quiescence. Nature, 2012. 490(7420): p. 355-60.
39. Hannon, K., et al., Differentially expressed fibroblast growth factors regulate skeletal muscle development through autocrine and paracrine mechanisms. J Cell Biol, 1996. 132(6): p. 1151-9.
40. Rao, N., et al., Fibroblasts influence muscle progenitor differentiation and alignment in contact independent and dependent manners in organized co-culture devices. Biomed Microdevices, 2013. 15(1): p. 161-9.
41. DiMario, J., et al., Fibroblast growth factor in the extracellular matrix of dystrophic (mdx) mouse muscle. Science, 1989. 244(4905): p. 688-90.
42. Olwin, B.B. and S.D. Hauschka, Identification of the fibroblast growth factor receptor of Swiss 3T3 cells and mouse skeletal muscle myoblasts. Biochemistry, 1986. 25(12): p. 3487-92.
43. Yablonka-Reuveni, Z., et al., Myogenic-specific ablation of Fgfr1 impairs FGF2-mediated proliferation of satellite cells at the myofiber niche but does not abolish the capacity for muscle regeneration. Front Aging Neurosci, 2015. 7: p. 85.
44. Cornelison, D.D., et al., Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration. Dev Biol, 2001. 239(1): p. 79-94.
45. Eswarakumar, V.P., I. Lax, and J. Schlessinger, Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev, 2005. 16(2): p. 139-49.
46. Ornitz, D.M. and N. Itoh, The Fibroblast Growth Factor signaling pathway. Wiley Interdiscip Rev Dev Biol, 2015. 4(3): p. 215-66.
47. Bernet, J.D., et al., p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice. Nat Med, 2014. 20(3): p. 265-71.
48. Templeton, T.J. and S.D. Hauschka, FGF-mediated aspects of skeletal muscle growth and differentiation are controlled by a high affinity receptor, FGFR1. Dev Biol, 1992. 154(1): p. 169-81.
49. Kudla, A.J., et al., A requirement for fibroblast growth factor in regulation of skeletal muscle growth and differentiation cannot be replaced by activation of platelet-derived growth factor signaling pathways. Mol Cell Biol, 1995. 15(6): p. 3238-46.
50. Rapraeger, A.C., A. Krufka, and B.B. Olwin, Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation. Science, 1991. 252(5013): p. 1705-8.
51. Olwin, B.B. and A. Rapraeger, Repression of myogenic differentiation by aFGF, bFGF, and K-FGF is dependent on cellular heparan sulfate. J Cell Biol, 1992. 118(3): p. 631-9.
52. Rapraeger, A.C., et al., Regulation by heparan sulfate in fibroblast growth factor signaling. Methods Enzymol, 1994. 245: p. 219-40.
53. Amaya, E., et al., FGF signalling in the early specification of mesoderm in Xenopus. Development, 1993. 118(2): p. 477-87.
54. Riley, B.B., et al., Retroviral expression of FGF-2 (bFGF) affects patterning in chick limb bud. Development, 1993. 118(1): p. 95-104.
55. Fallon, J.F., et al., FGF-2: apical ectodermal ridge growth signal for chick limb development. Science, 1994. 264(5155): p. 104-7.
56. Savage, M.P., et al., Distribution of FGF-2 suggests it has a role in chick limb bud growth. Dev Dyn, 1993. 198(3): p. 159-70.
57. Niswander, L., et al., A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature, 1994. 371(6498): p. 609-12.
58. Crossley, P.H. and G.R. Martin, The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. Development, 1995. 121(2): p. 439-51.
59. Cohn, M.J., et al., Fibroblast growth factors induce additional limb development from the flank of chick embryos. Cell, 1995. 80(5): p. 739-46.
60. Crossley, P.H., et al., Roles for FGF8 in the induction, initiation, and maintenance of chick limb development. Cell, 1996. 84(1): p. 127-36.
61. Fearon, K., et al., Definition and classification of cancer cachexia: an international consensus. Lancet Oncol, 2011. 12(5): p. 489-95.
62. Stephens, N.A., et al., Sexual dimorphism modulates the impact of cancer cachexia on lower limb muscle mass and function. Clin Nutr, 2012. 31(4): p. 499-505.
63. Martin, A. and D. Freyssenet, Phenotypic features of cancer cachexia-related loss of skeletal muscle mass and function: lessons from human and animal studies. J Cachexia Sarcopenia Muscle, 2021. 12(2): p. 252-273.
64. Houten, L. and A.A. Reilley, An investigation of the cause of death from cancer. J Surg Oncol, 1980. 13(2): p. 111-6.
65. Sartori, R., V. Romanello, and M. Sandri, Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun, 2021. 12(1): p. 330.
66. Yang, W., et al., Molecular mechanisms of cancer cachexia‑induced muscle atrophy (Review). Mol Med Rep, 2020. 22(6): p. 4967-4980.
67. Bowen, T.S., G. Schuler, and V. Adams, Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle, 2015. 6(3): p. 197-207.
68. Mammucari, C., et al., FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab, 2007. 6(6): p. 458-71.
69. Bodine, S.C., et al., Identification of ubiquitin ligases required for skeletal muscle atrophy. Science, 2001. 294(5547): p. 1704-8.
70. Cai, D., et al., IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell, 2004. 119(2): p. 285-98.
71. Rom, O. and A.Z. Reznick, The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass. Free Radic Biol Med, 2016. 98: p. 218-230.
72. Kaisari, S., et al., Involvement of NF-kappaB and muscle specific E3 ubiquitin ligase MuRF1 in cigarette smoke-induced catabolism in C2 myotubes. Adv Exp Med Biol, 2013. 788: p. 7-17.
73. McClung, J.M., et al., p38 MAPK links oxidative stress to autophagy-related gene expression in cachectic muscle wasting. Am J Physiol Cell Physiol, 2010. 298(3): p. C542-9.
74. Fearon, K.C., D.J. Glass, and D.C. Guttridge, Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab, 2012. 16(2): p. 153-66.
75. Petruzzelli, M. and E.F. Wagner, Mechanisms of metabolic dysfunction in cancer-associated cachexia. Genes Dev, 2016. 30(5): p. 489-501.
76. Bonaldo, P. and M. Sandri, Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech, 2013. 6(1): p. 25-39.
77. Grabiec, A.M., et al., Histone deacetylase inhibitors suppress rheumatoid arthritis fibroblast-like synoviocyte and macrophage IL-6 production by accelerating mRNA decay. Ann Rheum Dis, 2012. 71(3): p. 424-31.
78. Miki, S., et al., Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas. FEBS Lett, 1989. 250(2): p. 607-10.
79. Iwase, S., et al., Steep elevation of blood interleukin-6 (IL-6) associated only with late stages of cachexia in cancer patients. Eur Cytokine Netw, 2004. 15(4): p. 312-6.
80. Fujimoto-Ouchi, K., et al., Capecitabine improves cancer cachexia and normalizes IL-6 and PTHrP levels in mouse cancer cachexia models. Cancer Chemother Pharmacol, 2007. 59(6): p. 807-15.
81. White, J.P., et al., Muscle oxidative capacity during IL-6-dependent cancer cachexia. Am J Physiol Regul Integr Comp Physiol, 2011. 300(2): p. R201-11.
82. Op den Kamp, C.M., et al., Preserved muscle oxidative metabolic phenotype in newly diagnosed non-small cell lung cancer cachexia. J Cachexia Sarcopenia Muscle, 2015. 6(2): p. 164-73.
83. Bonetto, A., et al., JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab, 2012. 303(3): p. E410-21.
84. Eskiler, G.G., et al., IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia. Bratisl Lek Listy, 2019. 66(11): p. 819-826.
85. Pin, F., et al., Growth of ovarian cancer xenografts causes loss of muscle and bone mass: a new model for the study of cancer cachexia. J Cachexia Sarcopenia Muscle, 2018. 9(4): p. 685-700.
86. White, J.P., et al., Muscle mTORC1 suppression by IL-6 during cancer cachexia: a role for AMPK. Am J Physiol Endocrinol Metab, 2013. 304(10): p. E1042-52.
87. Li, Y.P., et al., Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor necrosis factor alpha. FASEB J, 1998. 12(10): p. 871-80.
88. Li, Y.P., et al., TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J, 2005. 19(3): p. 362-70.
89. Guttridge, D.C., et al., NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science, 2000. 289(5488): p. 2363-6.
90. Sandri, M., et al., Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell, 2004. 117(3): p. 399-412.
91. Judge, S.M., et al., Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia. BMC Cancer, 2014. 14: p. 997.
92. Liu, C.M., et al., Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice. Cancer Gene Ther, 2007. 14(12): p. 945-52.
93. Liu, D., B.L. Black, and R. Derynck, TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev, 2001. 15(22): p. 2950-66.
94. Milasincic, D.J., et al., Stimulation of C2C12 myoblast growth by basic fibroblast growth factor and insulin-like growth factor 1 can occur via mitogen-activated protein kinase-dependent and -independent pathways. Mol Cell Biol, 1996. 16(11): p. 5964-73.
95. Fan, S.H., et al., MyoD Over-Expression Rescues GST-bFGF Repressed Myogenesis. Int J Mol Sci, 2024. 25(8).
96. Wang, Z.G., et al., bFGF regulates autophagy and ubiquitinated protein accumulation induced by myocardial ischemia/reperfusion via the activation of the PI3K/Akt/mTOR pathway. Sci Rep, 2015. 5: p. 9287.
97. Figueroa, A., et al., Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes. Mol Cell Biol, 2003. 23(14): p. 4991-5004.
98. Wu, X. and L. Xu, The RNA-binding protein HuR in human cancer: A friend or foe? Adv Drug Deliv Rev, 2022. 184: p. 114179.
99. Janice Sanchez, B., et al., Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy. Nat Commun, 2019. 10(1): p. 4171.

指導教授

陳盛良(Shen-Liang Chen)

審核日期

2024-8-19

推文