(54.236.58.220) 您好!臺灣時間:2021/02/28 23:59
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:劉欣欣
研究生(外文):XINXIN LIU
論文名稱:長鏈非編碼RNA LINAT藉由控制正向回饋調節的TGF-β訊號通路來促進腫瘤進程
論文名稱(外文):Long non-coding RNA LINAT controls a positive feedback regulation of TGF-β signaling to promote tumor progression
指導教授:陳瑞華陳瑞華引用關係
指導教授(外文):Ruey-Hwa Chen
口試委員:周玉山張茂山
口試委員(外文):Yuh-Shan JouMau-Sun Chang
口試日期:2019-07-17
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生化科學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2019
畢業學年度:107
語文別:英文
論文頁數:52
中文關鍵詞:長鏈非編碼RNALINAT癌症進程皮細胞間質轉化
DOI:10.6342/NTU201901523
相關次數:
  • 被引用被引用:0
  • 點閱點閱:26
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
近些年,非常多研究指出長鏈非編碼RNA重要性,尤其是在癌症進程中。在這,我們研究一個新穎的腫瘤相關長鏈非編碼RNA,LINAT。臨床上,我們發現:LINAT高度表現和多種癌症病人的低生存率成正相關。進一步,LINAT過度表現和肝癌,乳癌病人中淋巴結入侵,惡化的病理學階段以及血管入侵成正相關。然而,LINAT表現量在正常及肝癌組織中沒有差異。這些結果暗示:LINAT在癌症進程中扮演重要角色,比如入侵或轉移階段,但不在腫瘤起始階段。我們為了揭示LINAT在癌症進程中角色,操作了LINAT的表現量。在結直腸癌,乳癌細胞中將LINAT過度或降低表現。結果顯示,LINAT誘導了惡性的病理學形態,包含上皮細胞間質轉化形態,轉移和入侵。為了揭示LINAT是如何誘導上皮細胞間質轉化,我們做了RNA定序,並用生資工具發現LINAT可能參與TGF-β訊號通路。實驗發現,TGF-β訊號通路中下游目標基因表現量及啟動子活性都在LINAT表現量降低時降低了。這表示了LINAT在TGF-β訊號通路中扮演促進者角色。我們進一步又發現Smad3/4介導的TGF-β也可誘導多種癌細胞中LINAT的表現。當我們降低LINAT表現量時,會降低TGF-β訊號通路的強度。因此,我們的研究指出LINAT會參與到一個回饋控制的TGF-β訊號通路。結論,我們找到一個新穎癌症相關的長鏈非編碼RNA, LINAT,且揭示了其在皮細胞間質轉化中及TGF-β訊號通路中的角色。LINAT所誘導的新穎正回饋調節之TGF-β訊號通路,突出其在癌症惡性中的角色。
Recent studies have emerged that long non-coding RNAs (lncRNAs) play vital role in tumor progression. Here, we identified a novel tumor related lncRNA termed LINAT (Long Intergenic Noncoding RNA Activated by TGF-β). Clinically, high expression of LINAT correlates with poor survival among colorectal, breast and liver cancer patients. Furthermore, LINAT overexpression is associated with lymph node invasion, deteriorated pathology stage as well as vascular invasion in liver and breast cancer patients. However, the expression level of LINAT has no significant difference between normal and tumor tissue. These findings imply that LINAT plays a role in tumor progression, such as invasion/metastasis, but not tumor initiation. To address the role of LINAT in tumor progression, we manipulated LINAT expression in breast and colorectal cancer cell lines by overexpression and knockdown approaches. The data revealed that LINAT induces malignant phenotypes, including epithelial-mesenchymal transition (EMT) phenotype, migration and invasion both in morphological and molecular levels. To uncover how LINAT induces EMT, we conducted RNA-seq to identify LINAT-induced transcriptome and utilized bioinformatics tools, including Ingenuity Pathway Analysis and Gene Set Enrichment Analysis, to characterize its features and compare with the signatures of different signaling pathways. Strikingly, LINAT-induced transcriptome has a significant correlation with the signature of TGF-β signaling. Consistently, both the expression level and promoter activity of TGF-β downstream genes are reduced significantly in LINAT knockdown lines, indicating a promoting role of LINAT in TGF-β signaling. We further found that TGF-β is able to induce LINAT expression in multiple tumor cell lines through a Smad3/4 dependent manner. Our following study shows that LINAT knockdown can decrease the amplitude and duration of TGF-β signaling. Thus, our data indicate that LINAT participates in a feedback control of TGF-β signaling. In conclusion, our results not only identify a novel tumor-promoting lncRNA, LINAT, but also dissect its role in EMT and TGF-β signaling. The LINAT-induced novel positive feedback regulation of TGF-β highlights its role in tumor malignancy and supports our findings from the clinical specimens.
謝辭 i
中文摘要 ii
Abstract iii
I. Introduction 01
1. Tumor progression and metastasis 01
2. TGF-β pathway 05
2.1 Overview of TGF-β pathway 05
2.2 Mechanism of TGF-β signaling pathway 07
2.3 The role of TGF-β pathway in EMT and metastasis 08
3. Long noncoding RNA (LncRNA) 10
3.1 Characteristics of long noncoding RNA 10
3.2 Molecular mechanism of long noncoding RNA 11
3.3 The functions of lncRNA in tumor progression and metastasis 13
4. LncRNA in TGF-β pathway 15
5. LINAT 16
II. Materials and Methods 18
Cell culture 18
Plasmids 18
Patient specimens 18
Lentivirus transduction 19
RNA extraction, RT/real-time PCR 20
Cell migration and invasion assays 21
Cell lysate preparation and western blot 21
Luciferase reporter assay and transfection 23
Subcellular fractionation assay. 23
Statistical Analysis 24
III. Results 25
LINAT expression correlates tumor progression and poor prognosis in several cancer types 25
LINAT induces malignant phenotypes in breast and colorectal cancer cell lines 26
LINAT - induced gene expression - an association with TGF-β signaling 27
LINAT knockdown impairs TGF-β signaling 27
LINAT is induced by TGF-β signaling through Smad3/4 28
LINAT is involved a feedback control of TGF-β signaling 29
IV. Discussion 30
V. References 34
VI. Figures 42
Figure 1. The clinical significance of LINAT in various cancer types 42
Figure 2. The expression levels of LINAT in various breast cancer cells 43
Figure 3. Knockdown of LINAT impairs EMT, migration and invasion 44
Figure 4. Overexpression of LINAT promotes EMT, migration and invasion 45
Figure 5. LINAT is mainly located at nucleus 46
Figure 6. Knockdown of LINAT reduces the expression of Smad target genes 47
Figure 7. Knockdown of LINAT reduces the promoter activity of Smad target genes 48
Figure 8. LINAT is induced by TGF-β signaling through Smad3/4 49
Figure 9. LINAT KD decreases the amplitude and duration of TGF-β induced genes expression 50
Figure 10. The model shows the mechanism for LINAT in TGF-β pathway 51
VII. Appendix 52
Alcorn JF, Guala AS, van der Velden J, McElhinney B, Irvin CG, Davis RJ, Janssen-Heininger YM. 2008. Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-beta1. J Cell Sci 121:1036-1045.
Ansieau S, et al. 2008. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell 14:79-89.
Araujo-Jorge TC, Waghabi MC, Soeiro Mde N, Keramidas M, Bailly S, Feige JJ. 2008. Pivotal role for TGF-beta in infectious heart disease: The case of Trypanosoma cruzi infection and consequent Chagasic myocardiopathy. Cytokine Growth Factor Rev 19:405-413.
Brown JM. 2000. Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Mol Med Today 6:157-162.
Bruna A, et al. 2007. High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell 11:147-160.
Buck MB, Knabbe C. 2006. TGF-beta signaling in breast cancer. Ann N Y Acad Sci 1089:119-126.
Carlini MJ, De Lorenzo MS, Puricelli L. 2011. Cross-talk between tumor cells and the microenvironment at the metastatic niche. Curr Pharm Biotechnol 12:1900-1908.
Chaffer CL, Weinberg RA. 2011. A perspective on cancer cell metastasis. Science 331:1559-1564.
Chang H, Brown CW, Matzuk MM. 2002. Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 23:787-823.
Cho HJ, Baek KE, Saika S, Jeong MJ, Yoo J. 2007. Snail is required for transforming growth factor-beta-induced epithelial-mesenchymal transition by activating PI3 kinase/Akt signal pathway. Biochem Biophys Res Commun 353:337-343.
Dai FQ, Li CR, Fan XQ, Tan L, Wang RT, Jin H. 2019. miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and beta-Catenin Signaling. Mol Ther Nucleic Acids 16:675-685.
Derynck R, Akhurst RJ, Balmain A. 2001. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29:117-129.
Fabregat I, Fernando J, Mainez J, Sancho P. 2014. TGF-beta signaling in cancer treatment. Curr Pharm Des 20:2934-2947.
Feng XH, Derynck R. 2005. Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol 21:659-693.
Figueroa JD, et al. 2010. Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics. Breast Cancer Res Treat 121:727-735.
Foletta VC, Lim MA, Soosairajah J, Kelly AP, Stanley EG, Shannon M, He W, Das S, Massague J, Bernard O. 2003. Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. J Cell Biol 162:1089-1098.
Friedl P, Wolf K. 2003. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362-374.
Gay LJ, Felding-Habermann B. 2011. Contribution of platelets to tumour metastasis. Nat Rev Cancer 11:123-134.
Grimshaw MJ, Hagemann T, Ayhan A, Gillett CE, Binder C, Balkwill FR. 2004. A role for endothelin-2 and its receptors in breast tumor cell invasion. Cancer Res 64:2461-2468.
Guise T. 2010. Examining the metastatic niche: targeting the microenvironment. Semin Oncol 37 Suppl 2:S2-14.
Gupta GP, Nguyen DX, Chiang AC, Bos PD, Kim JY, Nadal C, Gomis RR, Manova-Todorova K, Massague J. 2007. Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446:765-770.
Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100:57-70.
Hegarty SV, Sullivan AM, O''Keeffe GW. 2014. Roles for the TGFbeta superfamily in the development and survival of midbrain dopaminergic neurons. Mol Neurobiol 50:559-573.
Higgins SP, Tang Y, Higgins CE, Mian B, Zhang W, Czekay RP, Samarakoon R, Conti DJ, Higgins PJ. 2018. TGF-beta1/p53 signaling in renal fibrogenesis. Cell Signal 43:1-10.
Hoot KE, Lighthall J, Han G, Lu SL, Li A, Ju W, Kulesz-Martin M, Bottinger E, Wang XJ. 2008. Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression. J Clin Invest 118:2722-2732.
Hu J, Xu J, Li M, Zhang Y, Yi H, Chen J, Dong L, Zhang J, Huang Z. 2019. Targeting Lymph Node Sinus Macrophages to Inhibit Lymph Node Metastasis. Mol Ther Nucleic Acids 16:650-662.
Ikushima H, Miyazono K. 2010. Cellular context-dependent "colors" of transforming growth factor-beta signaling. Cancer Sci 101:306-312.
---. 2012. TGF-beta signal transduction spreading to a wider field: a broad variety of mechanisms for context-dependent effects of TGF-beta. Cell Tissue Res 347:37-49.
Imamura T, Hikita A, Inoue Y. 2012. The roles of TGF-beta signaling in carcinogenesis and breast cancer metastasis. Breast Cancer 19:118-124.
Incardona F, Doroudchi MM, Ismail N, Carreno A, Griner E, Anna Lim M, Reproducibility Project: Cancer B. 2015. Registered report: Interactions between cancer stem cells and their niche govern metastatic colonization. Elife 4:e06938.
Jakowlew SB. 2006. Transforming growth factor-beta in cancer and metastasis. Cancer Metastasis Rev 25:435-457.
Jorda M, Olmeda D, Vinyals A, Valero E, Cubillo E, Llorens A, Cano A, Fabra A. 2005. Upregulation of MMP-9 in MDCK epithelial cell line in response to expression of the Snail transcription factor. J Cell Sci 118:3371-3385.
Kano MR, et al. 2007. Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-beta signaling. Proc Natl Acad Sci U S A 104:3460-3465.
Kelly RJ, Morris JC. 2010. Transforming growth factor-beta: a target for cancer therapy. J Immunotoxicol 7:15-26.
Khoshakhlagh M, Soleimani A, Binabaj MM, Avan A, Ferns GA, Khazaei M, Hassanian SM. 2019. Therapeutic potential of pharmacological TGF-beta signaling pathway inhibitors in the pathogenesis of breast cancer. Biochem Pharmacol 164:17-22.
Ko YH, Lin Z, Flomenberg N, Pestell RG, Howell A, Sotgia F, Lisanti MP, Martinez-Outschoorn UE. 2011. Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: implications for preventing chemotherapy resistance. Cancer Biol Ther 12:1085-1097.
Labelle M, Begum S, Hynes RO. 2011. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20:576-590.
Leivonen SK, Kahari VM. 2007. Transforming growth factor-beta signaling in cancer invasion and metastasis. Int J Cancer 121:2119-2124.
Liotta LA. 1986. Tumor invasion and metastases--role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res 46:1-7.
Liotta LA, Kleinerman J, Catanzaro P, Rynbrandt D. 1977. Degradation of basement membrane by murine tumor cells. J Natl Cancer Inst 58:1427-1431.
Lozar T, Gersak K, Cemazar M, Kuhar CG, Jesenko T. 2019. The biology and clinical potential of circulating tumor cells. Radiol Oncol.
Massague J. 2000. How cells read TGF-beta signals. Nat Rev Mol Cell Biol 1:169-178.
Massari ME, Murre C. 2000. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 20:429-440.
Miettinen PJ, Ebner R, Lopez AR, Derynck R. 1994. TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J Cell Biol 127:2021-2036.
Moreno-Bueno G, Portillo F, Cano A. 2008. Transcriptional regulation of cell polarity in EMT and cancer. Oncogene 27:6958-6969.
Moustakas A, Heldin CH. 2005. Non-Smad TGF-beta signals. J Cell Sci 118:3573-3584.
Nieswandt B, Hafner M, Echtenacher B, Mannel DN. 1999. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res 59:1295-1300.
Oskarsson T, Acharyya S, Zhang XH, Vanharanta S, Tavazoie SF, Morris PG, Downey RJ, Manova-Todorova K, Brogi E, Massague J. 2011. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med 17:867-874.
Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, Massague J. 2008. TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133:66-77.
Peinado H, Olmeda D, Cano A. 2007. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7:415-428.
Piek E, Moustakas A, Kurisaki A, Heldin CH, ten Dijke P. 1999. TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. J Cell Sci 112 ( Pt 24):4557-4568.
Postigo AA, Depp JL, Taylor JJ, Kroll KL. 2003. Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins. EMBO J 22:2453-2462.
Psaila B, Kaplan RN, Port ER, Lyden D. 2006. Priming the ''soil'' for breast cancer metastasis: the pre-metastatic niche. Breast Dis 26:65-74.
Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW. 2011. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475:222-225.
Quigley JP, Armstrong PB. 1998. Tumor cell intravasation alu-cidated: the chick embryo opens the window. Cell 94:281-284.
Sahai E. 2005. Mechanisms of cancer cell invasion. Curr Opin Genet Dev 15:87-96.
Sameni M, Dosescu J, Moin K, Sloane BF. 2003. Functional imaging of proteolysis: stromal and inflammatory cells increase tumor proteolysis. Mol Imaging 2:159-175.
Sasahira T, Bosserhoff AK, Kirita T. 2018. The importance of melanoma inhibitory activity gene family in the tumor progression of oral cancer. Pathol Int 68:278-286.
Sato M, Muragaki Y, Saika S, Roberts AB, Ooshima A. 2003. Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 112:1486-1494.
Savagner P, Yamada KM, Thiery JP. 1997. The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. J Cell Biol 137:1403-1419.
Seton-Rogers SE, Lu Y, Hines LM, Koundinya M, LaBaer J, Muthuswamy SK, Brugge JS. 2004. Cooperation of the ErbB2 receptor and transforming growth factor beta in induction of migration and invasion in mammary epithelial cells. Proc Natl Acad Sci U S A 101:1257-1262.
Syed V. 2016. TGF-beta Signaling in Cancer. J Cell Biochem 117:1279-1287.
Taki M, Verschueren K, Yokoyama K, Nagayama M, Kamata N. 2006. Involvement of Ets-1 transcription factor in inducing matrix metalloproteinase-2 expression by epithelial-mesenchymal transition in human squamous carcinoma cells. Int J Oncol 28:487-496.
Thiery JP. 2002. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442-454.
Valastyan S, Weinberg RA. 2011. Tumor metastasis: molecular insights and evolving paradigms. Cell 147:275-292.
Wolf MJ, et al. 2012. Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway. Cancer Cell 22:91-105.
Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, Zhou BP. 2009. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell 15:416-428.
Wyckoff JB, Jones JG, Condeelis JS, Segall JE. 2000. A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res 60:2504-2511.
Xu J, Lamouille S, Derynck R. 2009. TGF-beta-induced epithelial to mesenchymal transition. Cell Res 19:156-172.
Yadav H, et al. 2011. Protection from obesity and diabetes by blockade of TGF-beta/Smad3 signaling. Cell Metab 14:67-79.
Yagi K, Furuhashi M, Aoki H, Goto D, Kuwano H, Sugamura K, Miyazono K, Kato M. 2002. c-myc is a downstream target of the Smad pathway. J Biol Chem 277:854-861.
Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. 2004. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927-939.
Yang J, Mani SA, Weinberg RA. 2006. Exploring a new twist on tumor metastasis. Cancer Res 66:4549-4552.
You W, Hong Y, He H, Huang X, Tao W, Liang X, Zhang Y, Li X. 2019. TGF-beta mediates aortic smooth muscle cell senescence in Marfan syndrome. Aging (Albany NY).
Yuan Y, Jiang YC, Sun CK, Chen QM. 2016. Role of the tumor microenvironment in tumor progression and the clinical applications (Review). Oncol Rep 35:2499-2515.
Zi Z. 2019. Molecular Engineering of the TGF-beta Signaling Pathway. J Mol Biol.
Zhang L, Ridgway LD, Wetzel MD, Ngo J, Yin W, Kumar D, Goodman JC, Groves MD, Marchetti D. 2013. The identification and characterization of breast cancer CTCs competent for brain metastasis. Sci Transl Med 5:180ra148.
Wu Y, et al. 2012. The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer. Int J Oncol 41:1337-1346.
Carninci P, et al. 2005. The transcriptional landscape of the mammalian genome. Science 309:1559-1563.
Clark MB, Johnston RL, Inostroza-Ponta M, Fox AH, Fortini E, Moscato P, Dinger ME, Mattick JS. 2012. Genome-wide analysis of long noncoding RNA stability. Genome Res 22:885-898.
Dahariya S, Paddibhatla I, Kumar S, Raghuwanshi S, Pallepati A, Gutti RK. 2019. Long non-coding RNA: Classification, biogenesis and functions in blood cells. Mol Immunol 112:82-92.
Das M, Renganathan A, Dighe SN, Bhaduri U, Shettar A, Mukherjee G, Kondaiah P, Satyanarayana Rao MR. 2018. DDX5/p68 associated lncRNA LOC284454 is differentially expressed in human cancers and modulates gene expression. RNA Biol 15:214-230.
Derrien T, et al. 2012. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775-1789.
Fan C, et al. 2019. Long non-coding RNA LOC284454 promotes migration and invasion of nasopharyngeal carcinoma via modulating the Rho/Rac signaling pathway. Carcinogenesis 40:380-391.
Fang H, Declerck YA. 2013. Targeting the tumor microenvironment: from understanding pathways to effective clinical trials. Cancer Res 73:4965-4977.
Fang Y, Fullwood MJ. 2016. Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer. Genomics Proteomics Bioinformatics 14:42-54.
Farooqi AA, Attar R, Qureshi MZ, Fayyaz S, Sohail MI, Sabitaliyevich UY, Nurmurzayevich SB, Yelekenova A, Yaylim I, Alaaeddine N. 2018. Interplay of long non-coding RNAs and TGF/SMAD signaling in different cancers. Cell Mol Biol (Noisy-le-grand) 64:1-6.
Grote P, et al. 2013. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell 24:206-214.
Gulei D, Mehterov N, Ling H, Stanta G, Braicu C, Berindan-Neagoe I. 2017. The "good-cop bad-cop" TGF-beta role in breast cancer modulated by non-coding RNAs. Biochim Biophys Acta Gen Subj 1861:1661-1675.
Huarte M. 2015. The emerging role of lncRNAs in cancer. Nat Med 21:1253-1261.
Huarte M, et al. 2010. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142:409-419.
Labelle M, Begum S, Hynes RO. 2011. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20:576-590.
Lee S, Kopp F, Chang TC, Sataluri A, Chen B, Sivakumar S, Yu H, Xie Y, Mendell JT. 2016. Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins. Cell 164:69-80.
Liotta LA, Kohn EC. 2001. The microenvironment of the tumour-host interface. Nature 411:375-379.
Liu P, Yang H, Zhang J, Peng X, Lu Z, Tong W, Chen J. 2017. The lncRNA MALAT1 acts as a competing endogenous RNA to regulate KRAS expression by sponging miR-217 in pancreatic ductal adenocarcinoma. Sci Rep 7:5186.
Long Y, Wang X, Youmans DT, Cech TR. 2017. How do lncRNAs regulate transcription? Sci Adv 3:eaao2110.
Louro R, Smirnova AS, Verjovski-Almeida S. 2009. Long intronic noncoding RNA transcription: expression noise or expression choice? Genomics 93:291-298.
Lozar T, Gersak K, Cemazar M, Kuhar CG, Jesenko T. 2019. The biology and clinical potential of circulating tumor cells. Radiol Oncol.
Ma L, Bajic VB, Zhang Z. 2013. On the classification of long non-coding RNAs. RNA Biol 10:925-933.
Mondal T, et al. 2015. MEG3 long noncoding RNA regulates the TGF-beta pathway genes through formation of RNA-DNA triplex structures. Nat Commun 6:7743.
Nguyen VT, Kiss T, Michels AA, Bensaude O. 2001. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414:322-325.
Orimo A, Weinberg RA. 2006. Stromal fibroblasts in cancer: a novel tumor-promoting cell type. Cell Cycle 5:1597-1601.
Pan Y, Chen J, Tao L, Zhang K, Wang R, Chu X, Chen L. 2017. Long noncoding RNA ROR regulates chemoresistance in docetaxel-resistant lung adenocarcinoma cells via epithelial mesenchymal transition pathway. Oncotarget 8:33144-33158.
Qian M, et al. 2016. P50-associated COX-2 extragenic RNA (PACER) overexpression promotes proliferation and metastasis of osteosarcoma cells by activating COX-2 gene. Tumour Biol 37:3879-3886.
Rinn JL, et al. 2007. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311-1323.
Sannigrahi MK, Sharma R, Panda NK, Khullar M. 2018. Role of non-coding RNAs in head and neck squamous cell carcinoma: A narrative review. Oral Dis 24:1417-1427.
Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY. 2010. Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689-693.
Vance KW, Ponting CP. 2014. Transcriptional regulatory functions of nuclear long noncoding RNAs. Trends Genet 30:348-355.
Wang F, Ying HQ, He BS, Pan YQ, Deng QW, Sun HL, Chen J, Liu X, Wang SK. 2015. Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway. Oncotarget 6:7899-7917.
Wang SH, Zhang WJ, Wu XC, Weng MZ, Zhang MD, Cai Q, Zhou D, Wang JD, Quan ZW. 2016. The lncRNA MALAT1 functions as a competing endogenous RNA to regulate MCL-1 expression by sponging miR-363-3p in gallbladder cancer. J Cell Mol Med 20:2299-2308.
Wen Q, Liu Y, Lyu H, Xu X, Wu Q, Liu N, Yin Q, Li J, Sheng X. 2017. Long Noncoding RNA GAS5, Which Acts as a Tumor Suppressor via microRNA 21, Regulates Cisplatin Resistance Expression in Cervical Cancer. Int J Gynecol Cancer 27:1096-1108.
Wu J, Zhang J, Shen B, Yin K, Xu J, Gao W, Zhang L. 2015. Long noncoding RNA lncTCF7, induced by IL-6/STAT3 transactivation, promotes hepatocellular carcinoma aggressiveness through epithelial-mesenchymal transition. J Exp Clin Cancer Res 34:116.
Wyckoff JB, Jones JG, Condeelis JS, Segall JE. 2000. A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res 60:2504-2511.
Yuan JH, et al. 2014. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell 25:666-681.
Zhang Y, Tang L. 2018. The Application of lncRNAs in Cancer Treatment and Diagnosis. Recent Pat Anticancer Drug Discov 13:292-301.
Zhao B, et al. 2018. Overexpression of lncRNA ANRIL promoted the proliferation and migration of prostate cancer cells via regulating let-7a/TGF-beta1/ Smad signaling pathway. Cancer Biomark 21:613-620.
Zhao JJ, et al. 2016. Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer cells through TGF-beta/Smad signaling pathway. Oncotarget 7:57903-57918.
Zhao L, et al. 2017. Long Noncoding RNA LINC00092 Acts in Cancer-Associated Fibroblasts to Drive Glycolysis and Progression of Ovarian Cancer. Cancer Res 77:1369-1382.
Arun G, et al. 2016. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev 30:34-51.
Gutschner T, Hammerle M, Diederichs S. 2013. MALAT1 -- a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl) 91:791-801.
Ji P, et al. 2003. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22:8031-8041.
Yang F, Huo XS, Yuan SX, Zhang L, Zhou WP, Wang F, Sun SH. 2013. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell 49:1083-1096.
Ying L, Chen Q, Wang Y, Zhou Z, Huang Y, Qiu F. 2012. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst 8:2289-2294.
Consortium EP, et al. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816.
Wang KC, Chang HY. 2011. Molecular mechanisms of long noncoding RNAs. Mol Cell 43:904-914.
Imamura T, Hikita A, Inoue Y. 2012. The roles of TGF-beta signaling in carcinogenesis and breast cancer metastasis. Breast Cancer 19:118-124.
MR. 2018. DDX5/p68 associated lncRNA LOC284454 is differentially expressed in human cancers and modulates gene expression. RNA Biol 15:214-230.
Fan C, et al. 2019. Long non-coding RNA LOC284454 promotes migration and invasion of nasopharyngeal carcinoma via modulating the Rho/Rac signaling pathway. Carcinogenesis 40:380-391.
Chandran PA, et al. 2014. The TGF-beta-inducible miR-23a cluster attenuates IFN-gamma levels and antigen-specific cytotoxicity in human CD8(+) T cells. J Leukoc Biol 96:633-645.
Cao M, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y, Noro R, Yoshimura A, Cai L, Gemma A. 2012. MiR-23a regulates TGF-beta-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol 41:869-875.
Dai F, Duan X, Liang YY, Lin X, Feng XH. 2010. Coupling of dephosphorylation and nuclear export of Smads in TGF-beta signaling. Methods Mol Biol 647:125-137.
Duca M, Vekhoff P, Oussedik K, Halby L, Arimondo PB. 2008. The triple helix: 50 years later, the outcome. Nucleic Acids Res 36:5123-5138.
Ferre F, Colantoni A, Helmer-Citterich M. 2016. Revealing protein-lncRNA interaction. Brief Bioinform 17:106-116.
Gindin Y, Jiang Y, Francis P, Walker RL, Abaan OD, Zhu YJ, Meltzer PS. 2015. miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1. Front Genet 6:233.
Gong C, Li Z, Ramanujan K, Clay I, Zhang Y, Lemire-Brachat S, Glass DJ. 2015. A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation. Dev Cell 34:181-191.
Li G, Yang M, Zuo L, Wang MX. 2018. MELK as a potential target to control cell proliferation in triple-negative breast cancer MDA-MB-231 cells. Oncol Lett 15:9934-9940.
Niu D, Wang G, Wang X. 2015. Up-regulation of cyclin E in breast cancer via estrogen receptor pathway. Int J Clin Exp Med 8:910-915.
Swier L, Dzikiewicz-Krawczyk A, Winkle M, van den Berg A, Kluiver J. 2019. Intricate crosstalk between MYC and non-coding RNAs regulates hallmarks of cancer. Mol Oncol 13:26-45.
Tu AW, Luo K. 2007. Acetylation of Smad2 by the co-activator p300 regulates activin and transforming growth factor beta response. J Biol Chem 282:21187-21196.
Wang C, Wang L, Ding Y, Lu X, Zhang G, Yang J, Zheng H, Wang H, Jiang Y, Xu L. 2017. LncRNA Structural Characteristics in Epigenetic Regulation. Int J Mol Sci 18.
Yip CH, Rhodes A. 2014. Estrogen and progesterone receptors in breast cancer. Future Oncol 10:2293-2301.
Zhang A, Zhao JC, Kim J, Fong KW, Yang YA, Chakravarti D, Mo YY, Yu J. 2015. LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer. Cell Rep 13:209-221.
Lin X, et al. 2006. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell 125:915-928.
Clarke C, et al. 2013. Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis. Carcinogenesis 34:2300-2308.
Fan C, et al. 2019. Long non-coding RNA LOC284454 promotes migration and invasion of nasopharyngeal carcinoma via modulating the Rho/Rac signaling pathway. Carcinogenesis 40:380-391.
Gutschner T, Hammerle M, Diederichs S. 2013. MALAT1 -- a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl) 91:791-801.
Ji P, et al. 2003. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22:8031-8041.
Moustakas A, Heldin CH. 2005. Non-Smad TGF-beta signals. J Cell Sci 118:3573-3584.
Smith JJ, et al. 2010. Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. Gastroenterology 138:958-968.
Xu J, Lamouille S, Derynck R. 2009. TGF-beta-induced epithelial to mesenchymal transition. Cell Res 19:156-172.
Du M, et al. 2018. TGF- beta regulates the ERK/MAPK pathway independent of the SMAD pathway by repressing miRNA-124 to increase MALAT1 expression in nasopharyngeal carcinoma. Biomed Pharmacother 99:688-696.
Chandran PA, et al. 2014. The TGF-beta-inducible miR-23a cluster attenuates IFN-gamma levels and antigen-specific cytotoxicity in human CD8(+) T cells. J Leukoc Biol 96:633-645.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
無相關期刊
 
無相關點閱論文
 
系統版面圖檔 系統版面圖檔