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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊泮池(Pan-Chyr Yang) | |
| dc.contributor.author | Chen-En Yeh | en |
| dc.contributor.author | 葉陳恩 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:26:13Z | - |
| dc.date.available | 2017-09-25 | |
| dc.date.copyright | 2015-09-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-14 | |
| dc.identifier.citation | 1. Kratz, J.R., A. Yagui-Beltran, and D.M. Jablons, Cancer stem cells in lung tumorigenesis. Ann Thorac Surg, 2010. 89(6): p. S2090-5.
2. Perona, R., et al., A role for cancer stem cells in drug resistance and metastasis in non-small-cell lung cancer. Clin Transl Oncol, 2011. 13(5): p. 289-93. 3. Alamgeer, M., et al., Cancer stem cells in lung cancer: Evidence and controversies. Respirology, 2013. 18(5): p. 757-64. 4. Reya, T., et al., Stem cells, cancer, and cancer stem cells. Nature, 2001. 414(6859): p. 105-11. 5. Visvader, J.E. and G.J. Lindeman, Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer, 2008. 8(10): p. 755-68. 6. Al-Hajj, M., et al., Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A, 2003. 100(7): p. 3983-8. 7. Kim, C.F., et al., Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell, 2005. 121(6): p. 823-35. 8. Eramo, A., et al., Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ, 2008. 15(3): p. 504-14. 9. Zhang, W.C., et al., Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell, 2012. 148(1-2): p. 259-72. 10. O'Brien, C.A., et al., A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 2007. 445(7123): p. 106-10. 11. Ricci-Vitiani, L., et al., Identification and expansion of human colon-cancer-initiating cells. Nature, 2007. 445(7123): p. 111-5. 12. Li, C., et al., Identification of pancreatic cancer stem cells. Cancer Res, 2007. 67(3): p. 1030-7. 13. Patrawala, L., et al., Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene, 2006. 25(12): p. 1696-708. 14. Fang, D., et al., A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res, 2005. 65(20): p. 9328-37. 15. Bonnet, D. and J.E. Dick, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med, 1997. 3(7): p. 730-7. 16. Blair, A., et al., Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood, 1997. 89(9): p. 3104-12. 17. Blair, A., D.E. Hogge, and H.J. Sutherland, Most acute myeloid leukemia progenitor cells with long-term proliferative ability in vitro and in vivo have the phenotype CD34(+)/CD71(-)/HLA-DR. Blood, 1998. 92(11): p. 4325-35. 18. Blair, A. and H.J. Sutherland, Primitive acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo lack surface expression of c-kit (CD117). Exp Hematol, 2000. 28(6): p. 660-71. 19. Dalerba, P., et al., Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A, 2007. 104(24): p. 10158-63. 20. Collins, A.T., et al., Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res, 2005. 65(23): p. 10946-51. 21. van den Hoogen, C., et al., High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer. Cancer Res, 2010. 70(12): p. 5163-73. 22. Ginestier, C., et al., ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell, 2007. 1(5): p. 555-67. 23. Clarke, M.F., et al., Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res, 2006. 66(19): p. 9339-44. 24. Ponti, D., et al., Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res, 2005. 65(13): p. 5506-11. 25. Shmelkov, S.V., et al., CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest, 2008. 118(6): p. 2111-20. 26. Bertolini, G., et al., Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci U S A, 2009. 106(38): p. 16281-6. 27. Leung, E.L., et al., Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One, 2010. 5(11): p. e14062. 28. Qiu, X., et al., Characterization of sphere-forming cells with stem-like properties from the small cell lung cancer cell line H446. Cancer Lett, 2012. 323(2): p. 161-70. 29. Kastan, M.B., et al., Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells. Blood, 1990. 75(10): p. 1947-50. 30. Storms, R.W., et al., Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci U S A, 1999. 96(16): p. 9118-23. 31. Jiang, F., et al., Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res, 2009. 7(3): p. 330-8. 32. Sullivan, J.P., et al., Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer Res, 2010. 70(23): p. 9937-48. 33. Plaks, V., N. Kong, and Z. Werb, The Cancer Stem Cell Niche: How Essential Is the Niche in Regulating Stemness of Tumor Cells? Cell Stem Cell, 2015. 16(3): p. 225-238. 34. Chen, J.J., et al., Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Clin Cancer Res, 2003. 9(2): p. 729-37. 35. Albini, A., et al., Tumor inflammatory angiogenesis and its chemoprevention. Cancer Res, 2005. 65(23): p. 10637-41. 36. Kalluri, R. and M. Zeisberg, Fibroblasts in cancer. Nat Rev Cancer, 2006. 6(5): p. 392-401. 37. Hanahan, D. and L.M. Coussens, Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell, 2012. 21(3): p. 309-22. 38. Charles, N., et al., Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell, 2010. 6(2): p. 141-52. 39. Chen, W.J., et al., Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling. Nat Commun, 2014. 5: p. 3472. 40. Bao, S., et al., Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res, 2006. 66(16): p. 7843-8. 41. Korkaya, H., S. Liu, and M.S. Wicha, Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest, 2011. 121(10): p. 3804-9. 42. Gupta, G.P. and J. Massague, Cancer metastasis: building a framework. Cell, 2006. 127(4): p. 679-95. 43. Valastyan, S. and R.A. Weinberg, Tumor metastasis: molecular insights and evolving paradigms. Cell, 2011. 147(2): p. 275-92. 44. Mani, S.A., et al., The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 2008. 133(4): p. 704-15. 45. Cordenonsi, M., et al., The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell, 2011. 147(4): p. 759-72. 46. Wellner, U., et al., The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol, 2009. 11(12): p. 1487-95. 47. Chaffer, C.L., et al., Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell, 2013. 154(1): p. 61-74. 48. Wightman, B., et al., Negative regulatory sequences in the lin-14 3'-untranslated region are necessary to generate a temporal switch during Caenorhabditis elegans development. Genes Dev, 1991. 5(10): p. 1813-24. 49. Lee, R.C., R.L. Feinbaum, and V. Ambros, The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 1993. 75(5): p. 843-54. 50. Wightman, B., I. Ha, and G. Ruvkun, Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 1993. 75(5): p. 855-62. 51. Carthew, R.W. and E.J. Sontheimer, Origins and Mechanisms of miRNAs and siRNAs. Cell, 2009. 136(4): p. 642-55. 52. Kim, V.N., J. Han, and M.C. Siomi, Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol, 2009. 10(2): p. 126-39. 53. Krol, J., I. Loedige, and W. Filipowicz, The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet, 2010. 11(9): p. 597-610. 54. Filipowicz, W., S.N. Bhattacharyya, and N. Sonenberg, Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet, 2008. 9(2): p. 102-14. 55. Lin, P.Y., S.L. Yu, and P.C. Yang, MicroRNA in lung cancer. Br J Cancer, 2010. 103(8): p. 1144-8. 56. Di Leva, G., M. Garofalo, and C.M. Croce, MicroRNAs in cancer. Annu Rev Pathol, 2014. 9: p. 287-314. 57. Schramedei, K., et al., MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4. Oncogene, 2011. 30(26): p. 2975-85. 58. Kim, J., et al., Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci U S A, 2004. 101(1): p. 360-5. 59. Weber, M.J., New human and mouse microRNA genes found by homology search. FEBS J, 2005. 272(1): p. 59-73. 60. Landgraf, P., et al., A mammalian microRNA expression atlas based on small RNA library sequencing. Cell, 2007. 129(7): p. 1401-14. 61. Fakhry, M., et al., Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts. World J Stem Cells, 2013. 5(4): p. 136-48. 62. Lowery, A.J., et al., MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res, 2009. 11(3): p. R27. 63. Khatri, R. and S. Subramanian, MicroRNA-135b and Its Circuitry Networks as Potential Therapeutic Targets in Colon Cancer. Front Oncol, 2013. 3: p. 268. 64. Tong, A.W., et al., MicroRNA profile analysis of human prostate cancers. Cancer Gene Ther, 2009. 16(3): p. 206-16. 65. Lin, C.W., T.M. Hong, and P.C. Yang, MicroRNA-135b as therapeutic target in cancers. Rna & Disease, 2014. 1. 66. Rosen, V., BMP2 signaling in bone development and repair. Cytokine Growth Factor Rev, 2009. 20(5-6): p. 475-80. 67. Li, Z., et al., A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc Natl Acad Sci U S A, 2008. 105(37): p. 13906-11. 68. Schaap-Oziemlak, A.M., et al., MicroRNA hsa-miR-135b regulates mineralization in osteogenic differentiation of human unrestricted somatic stem cells. Stem Cells Dev, 2010. 19(6): p. 877-85. 69. Xu, S., et al., Upregulation of miR-135b is involved in the impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients. PLoS One, 2013. 8(11): p. e79752. 70. Bhinge, A., et al., MiR-135b is a direct PAX6 target and specifies human neuroectoderm by inhibiting TGF-beta/BMP signaling. EMBO J, 2014. 33(11): p. 1271-83. 71. Liu, C., et al., MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma. Blood, 2013. 122(12): p. 2083-92. 72. Bandres, E., et al., Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer, 2006. 5: p. 29. 73. Lin, C.W., et al., MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. Nat Commun, 2013. 4: p. 1877. 74. Nagel, R., et al., Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res, 2008. 68(14): p. 5795-802. 75. Necela, B.M., et al., Differential expression of microRNAs in tumors from chronically inflamed or genetic (APC(Min/+)) models of colon cancer. PLoS One, 2011. 6(4): p. e18501. 76. Valeri, N., et al., MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer. Cancer Cell, 2014. 25(4): p. 469-83. 77. Rowan, A.J., et al., APC mutations in sporadic colorectal tumors: A mutational 'hotspot' and interdependence of the 'two hits'. Proc Natl Acad Sci U S A, 2000. 97(7): p. 3352-7. 78. Jones, S., et al., Comparative lesion sequencing provides insights into tumor evolution. Proc Natl Acad Sci U S A, 2008. 105(11): p. 4283-8. 79. Krausova, M. and V. Korinek, Wnt signaling in adult intestinal stem cells and cancer. Cell Signal, 2014. 26(3): p. 570-9. 80. Arigoni, M., et al., miR-135b coordinates progression of ErbB2-driven mammary carcinomas through suppression of MID1 and MTCH2. Am J Pathol, 2013. 182(6): p. 2058-70. 81. Sanchez-Diaz, P.C., et al., De-regulated microRNAs in pediatric cancer stem cells target pathways involved in cell proliferation, cell cycle and development. PLoS One, 2013. 8(4): p. e61622. 82. Wormald, S. and D.J. Hilton, Inhibitors of cytokine signal transduction. J Biol Chem, 2004. 279(2): p. 821-4. 83. Kario, E., et al., Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem, 2005. 280(8): p. 7038-48. 84. Krebs, D.L., et al., SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. Mol Cell Biol, 2002. 22(13): p. 4567-78. 85. Bullock, A.N., et al., Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. Structure, 2007. 15(11): p. 1493-504. 86. Sasi, W., et al., Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer. BMC Cancer, 2010. 10: p. 178. 87. Scheitz, C.J., et al., Defining a tissue stem cell-driven Runx1/Stat3 signalling axis in epithelial cancer. EMBO J, 2012. 31(21): p. 4124-39. 88. Calvisi, D.F., et al., Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. J Clin Invest, 2007. 117(9): p. 2713-22. 89. Dontu, G., et al., In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev, 2003. 17(10): p. 1253-70. 90. Pastrana, E., V. Silva-Vargas, and F. Doetsch, Eyes wide open: a critical review of sphere-formation as an assay for stem cells. Cell Stem Cell, 2011. 8(5): p. 486-98. 91. He, S., D. Nakada, and S.J. Morrison, Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol, 2009. 25: p. 377-406. 92. Young, R.A., Control of the embryonic stem cell state. Cell, 2011. 144(6): p. 940-54. 93. Sutherland, J.M., et al., Suppressor of cytokine signaling 4 (SOCS4): moderator of ovarian primordial follicle activation. J Cell Physiol, 2012. 227(3): p. 1188-98. 94. Chuthapisith, S., et al., Breast cancer chemoresistance: emerging importance of cancer stem cells. Surg Oncol, 2010. 19(1): p. 27-32. 95. Anderson, E.C., et al., The role of colorectal cancer stem cells in metastatic disease and therapeutic response. Cancers (Basel), 2011. 3(1): p. 319-39. 96. Yu, F., et al., Mir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells. Oncogene, 2010. 29(29): p. 4194-204. 97. Wang, Y., et al., Transforming growth factor-beta regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and ATM. Oncogene, 2011. 30(12): p. 1470-80. 98. Bartucci, M., et al., TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells. Oncogene, 2015. 34(6): p. 681-90. 99. Hao, N.B., et al., Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol, 2012. 2012: p. 948098. 100. Aldinucci, D. and A. Colombatti, The inflammatory chemokine CCL5 and cancer progression. Mediators Inflamm, 2014. 2014: p. 292376. 101. Chung, F.T., et al., Tumor-associated macrophages correlate with response to epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small cell lung cancer. Int J Cancer, 2012. 131(3): p. E227-35. 102. Ohtaki, Y., et al., Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma. J Thorac Oncol, 2010. 5(10): p. 1507-15. 103. Takanami, I., K. Takeuchi, and S. Kodaira, Tumor-associated macrophage infiltration in pulmonary adenocarcinoma: association with angiogenesis and poor prognosis. Oncology, 1999. 57(2): p. 138-42. 104. Zhang, B., et al., M2-Polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma. Clinics, 2011. 66(11): p. 1879-1886. 105. Waugh, D.J. and C. Wilson, The interleukin-8 pathway in cancer. Clin Cancer Res, 2008. 14(21): p. 6735-41. 106. Wang, S.W., et al., CCL5/CCR5 axis induces vascular endothelial growth factor-mediated tumor angiogenesis in human osteosarcoma microenvironment. Carcinogenesis, 2015. 36(1): p. 104-14. 107. Long, H., et al., CD133(+) ovarian cancer stem-like cells promote non-stem cancer cell metastasis via CCL5 induced epithelial-mesenchymal transition. Oncotarget, 2015. 6(8): p. 5846-59. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52756 | - |
| dc.description.abstract | 肺癌(主要為非小細胞肺癌)是國人及世界上因癌症造成死亡的主要原因之一。其治療的過程中常有許多困難及阻礙，例如：肺癌轉移、癌症復發。近期研究指出腫瘤中的癌幹細胞(CSCs)可能是主要造成原因。微核醣核酸(miRNAs)是小片段且非編碼的(non-coding RNA)的單股內生性RNA，藉由類似RNAi的方式抑制並調控下游基因的表現繼而影響細胞增生、發育及凋亡。特定的微核醣核酸同時也被發現在癌症中扮演抑癌基因或是致癌基因的角色，透過直接或間接調控下游基因群的表現，使正常細胞癌化或是腫瘤惡化。
在實驗室過去的研究發現微核醣核酸-135b(miR-135b)的表現不論在體外(in vitro)或體內(in vivo)的實驗中都與肺癌細胞的轉移能力呈現高度正相關。在本篇論文中，我們發現在非小細胞肺癌細胞株(NSCLC cell line)中過量表現miR-135b能夠增強其幹性及自我更新的能力。相對地，以miR-135b抑制劑(antogmiR-135b)來抑制其表現則減少幹性。透過驗證幹性標記：Oct-4、Nanog、Sox2，也發現這些幹性標記在miR-135b過量表現時會有不同程度的影響。抑制細胞激素訊號四(suppressor of cytokine signaling 4, SOCS4)為我們鑑定的潛在miR-135b標靶之一。我們利用螢光素酶檢測系統驗證SOCS4的下游不轉綠序列(3’-UTR)在miR-135b 存在時，其表現會被抑制。經由逆轉錄聚合酶鏈式反應(RT-PCR)發現內生性SOCS4的訊息核糖核酸(mRNA)並不會受到過量表現的miR-135b影響，然而其內生性蛋白質是否會受到miR-135b的調控仍尚待驗證。利用已建立的HA標記SOCS4的質體(HA-SOCS4 plasmid)，我們發現在NSCLC cell line中過量表現HA-SOCS4能夠抑制其幹性；並可能透過參與在miR-135b所調控的幹性路徑中來抑制其幹性及自我更新的能力。此外我們利用人類細胞激素陣列(human cytokine array)分析，發現在NSCLC cell line中過量表現miR-135b會改變癌細胞原本的細胞激素分泌譜(secreted-cytokine profile)。 綜合以上的研究結果，我們了解miR-135b在調控非小細胞肺癌的幹性中扮演重要的角色，並可能透過改變癌細胞的細胞激素分泌譜而影響其與腫瘤微環境(tumor microenvironment)的交互作用；未來若能更進一步釐清miR-135b調控癌細胞幹性的機轉將有助於發展癌幹細胞標靶治療(CSCs targeting therapy)並幫助肺癌患者。 | zh_TW |
| dc.description.abstract | Dysregulation of microRNAs (miRNAs) had been shown to play a critical role in tumor progression and metastasis. Our lab previously demonstrated an oncogenic miRNA, miR-135b, can promote lung cancer invasion and metastasis. In this study, we identified miR-135b as a promoting cancer stemness miRNA in NSCLC.
Overexpression of miR-135b in non-small-cell lung carcinoma (NSCLC) cells promoted sphere-forming ability and its self-renewal ability in sphere formation assay and secondary sphere formation assay. Vice versa, knocked-down miR-135b decreased its sphere-forming ability. The expression of stemness markers: Oct-4, Nanog and Sox2 was affected by overexpression of miR-135b. The suppressor of cytokine signaling 4 (SOCS4) was predicted one of miR-135b putative target. In luciferase reporter assay, luciferase activity was decreased with present of miR-135b. In RT-PCR, endogenous SOCS4 mRNA expression was not affected by overexpression of miR-135b. Overexpression of SOCS4-expressing plasmid tag with HA (HA-SOCS4) in NSCLC cells suppressed sphere forming ability; and may suppress miR-135b-mediated stemness property and self-renewal ability as well. In addition, upon using human cytokine array, we observed that overexpressing miR-135b cancer cells showed different secreted-cytokine profile compared to the non-overexpressing group. Collectively, we understand that miR-135b play an important role in regulation of stemness in NSCLC and may affect the interaction of cancer cells with its microenvironment by modulation of cancer cells secreted-cytokine profile. Eventually, it should be helpful for lung cancer patients to clarify the detail mechanism of how miR-135b regulates cancer stemness and develop CSC targeting therapy in the future. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:26:13Z (GMT). No. of bitstreams: 1 ntu-104-R02448009-1.pdf: 2193417 bytes, checksum: 9eec0bf0ede45b8922eae271b69dd305 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 中文摘要 i
Abstract iii I. Introduction 6 1. Cancer stem cells 6 1.1 Cancer stem cells markers 7 1.2 Cancer stem cells markers in lung cancer 8 1.3 Cancer stem cells and tumor microenvironments 9 1.4 Cancer stem cells and metastasis 10 2. MicroRNAs (miRNAs) 11 2.1 miRNA-135b 12 2.1.1 miR-135b and cell fate decision 13 2.1.2 miR-135b and oncogenesis 14 3. Suppressor of cytokine signaling 4 (SOCS4) 16 II. Methods & Materials 18 1. Cell Culture 18 2. Infection of lentivirus 18 3. Ultra-low primary sphere-forming assay and secondary sphere forming assay 19 4. Human cytokine antibody array 19 5. Ribonucleic acids extraction 20 6. Western blot 20 7. Reverse-transcription polymerase chain reaction (RT-PCR) 21 8. Quantitative real time polymerase-chain reaction (qPCR) 21 9. Construction of SOCS4 expressing plasmid clone 23 10. Luciferase reporter vectors 23 11. Plasmid and siRNA Transfection 24 12. Luciferase reporter assay 24 III. Result 26 1. Overexpression of miR-135b increase stemness property in CL1-0 and CL141 NSCLC cell lines 26 2. Knockdown of miR-135b expression reduced stemness property in CL1-5 NSCLC cell line 27 3. Overexpression of miR-135b increases self-renewal ability in CL1-0 and CL141 NSCLC cell lines 28 4. miR-135b may affect the expression of stemness markers in NSCLC cell line 30 5. Stemness markers expression in miR-135b overexpressing spheres of NSCLC cell line 31 6. miR-135b targets 3’-UTR of SOCS4 in luciferase reporter assay 32 7. Endogenous suppressor of cytokine signaling 4 (SOCS4) mRNA expression level did not affected by overexpression of miR-135b 33 8. Overexpression of HA-SOCS4 reduced stemness property in CL141 NSCLC cell line 34 9. SOCS4 may represses miR-135b-mediated stemness property and self-renewal ability in NSCLC cell lines 35 10. Overexpression of miR-135b affected secreted cytokine profile of CL1-0 NSCLC cell line 37 IV. Discussion 39 V. Figures 45 Figure 1. Overexpression of miR-135b increase stemness property in CL1-0 NSCLC cell line 46 Figure 2. Overexpression of miR-135b increase stemness property in CL141 NSCLC cell line 49 Figure 3. Knockdown of miR-135b reduced stemness property in CL1-5 NSCLC cell line 52 Figure 4. Overexpression of miR-135b increase self-renewal ability in CL1-0 NSCLC cell line 55 Figure 5. Overexpression of miR-135b increase self-renewal ability in CL141 NSCLC cell line 58 Figure 6. miR-135b may affects stemness markers expression in NSCLC cell line 61 Figure 7. Stemness markers expression in overexpressing miR-135b spheres of NSCLC cell line 64 Figure 8. miR-135b down-regulated 3’-UTR of SOCS4 expression in luciferase reporter assay 67 Figure 9. Overexpression of miR-135b did not affect SOCS4 mRNA expression level 69 Figure 10. Manipulation of SOCS4 expression level 72 Figure 11. Overexpression of HA-SOCS4 decrease stemness property in CL141 NSCLC cell line 74 Figure 12. Overexpression of HA-SOCS4 may suppress stemness property in miR-135b-expressing lentiviral vector-transduced CL1-0 NSCLC cell line 76 Figure 13. Overexpression of HA-SOCS4 may suppress stemness property in miR-135b-expressing lentiviral vector-transduced CL141 NSCLC cell line 78 Figure 14. Overexpression of HA-SOCS4 may suppress self-renewal ability in miR-135b-expressing lentiviral vector-transduced CL1-0 NSCLC cell line 80 Figure 15. Overexpression of HA-SOCS4 may suppress self-renewal ability in miR-135b-expressing lentiviral vector-transduced CL141 NSCLC cell line 82 Figure 16. Overexpression of miR-135b affected secreted cytokine profile of CL1-0 NSCLC cell line 84 VI. Reference 85 | |
| dc.language.iso | en | |
| dc.subject | 微核醣核酸-135b | zh_TW |
| dc.subject | 肺癌 | zh_TW |
| dc.subject | 幹性 | zh_TW |
| dc.subject | 抑制細胞激素訊號四 | zh_TW |
| dc.subject | microRNA-135b | en |
| dc.subject | stemness | en |
| dc.subject | suppressor of cytokine signaling 4 | en |
| dc.subject | lung cancer | en |
| dc.title | 探討微核醣核酸-135b在肺癌幹性中所扮演的角色 | zh_TW |
| dc.title | Identification of the role of miR-135b in
lung cancer stemness | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 洪澤民(Tse-Ming Hung),吳君泰(June-Tai Wu) | |
| dc.subject.keyword | 肺癌,微核醣核酸-135b,幹性,抑制細胞激素訊號四, | zh_TW |
| dc.subject.keyword | lung cancer,microRNA-135b,stemness,suppressor of cytokine signaling 4, | en |
| dc.relation.page | 98 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-14 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-104-1.pdf 未授權公開取用 | 2.14 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。