腫瘤壞死因子-α誘發miR-450a去調節TMEM182的表現進而促使口腔鱗狀上皮細胞癌的轉移

簡易檢索 / 詳目顯示

回結果列表

研究生：	邢恩瑋 Hsing, En-Wei
論文名稱：	腫瘤壞死因子-α誘發miR-450a去調節TMEM182的表現進而促使口腔鱗狀上皮細胞癌的轉移 TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility
指導教授：	張俊彥 Chang, Jang-Yang 呂平江 Lyu, Ping-Chiang
口試委員:	夏興國 Shiah, Shine-Gwo 陳雅雯 Chen, Ya-Wen 王慧菁 Wang, Lily Hui-Ching
學位類別：	博士 Doctor
系所名稱：	生命科學暨醫學院 - 生物資訊與結構生物研究所 Institute of Bioinformatics and Structural Biology
論文出版年：	2020
畢業學年度：	108
語文別：	中文
論文頁數：	81
中文關鍵詞：	黏連、細胞外活化蛋白激酶、細胞外間質、侵犯、小分子核糖核酸、miR-450a 、核因子活化B細胞、TMEM182 、腫瘤壞死因子、onco-miRNA 、口腔癌、口腔鱗狀上皮細胞癌
外文關鍵詞：	adhesion, ERK1/2, ECM, invasion, miRNA, miR-450a, NFκB, TMEM182, TNF-α, oncomiRNA, oral cancer, oral squamous cell carcinoma
相關次數：	點閱：3 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

背景：口腔癌在台灣癌症發生率極高，而腫瘤的遠端轉移會使口腔癌病人的存活率降低，並提高癌症復發的可能性。口腔腫瘤細胞的發展中，異常的miRNAs 的表現與腫瘤發生及癌症惡化有關。我們發現儘管在罹患口腔癌(OSCC)的病人中，miR-450a在腫瘤組織的表現是有顯著的上升，但是針對致癌機制卻無相關研究。因此本研究欲探討miR-450a在OSCC癌症發展中，其分子層面上的機轉。
方法：利用即時定量聚合酶連鎖反應檢測miR-450a在OSCC癌症細胞株與病人 (35個群體樣本數)的表現量。經由資料庫與癌症病人基因表現進行分析比對，發現蛋白質分子TMEM182是miR-450a重要的靶基因。並進一步利用雙螢光素酶報告基因檢測和蛋白質的表現分析，驗證TMEM182與miR-450a的關聯性。使用細胞黏連實驗與細胞侵入實驗，探討miR-450a 與TMEM182兩者對於腫瘤細胞功能上的影響。TMEM182的表現與細胞內位置的判斷，是利用反轉錄聚合酶鏈式反應以及免疫螢光細胞染色進行分析。利用激酶抑制劑進一步驗證miR-450a在口腔癌細胞內的訊息傳遞機轉。
結果：在OSCC病人中，相較於鄰近正常細胞組織，miR-450a在腫瘤細胞中的表現量是高的。OSCC細胞株的檢測結果亦是如此。實驗結果發現，miR-450a會降低OSCC細胞對細胞外基質的黏連功能與誘發癌症細胞侵入性。此結果說明miR-450a在口腔癌上是扮演著oncomiR的角色。我們發現在OSCC細胞中，TMEM182是miR-450a的靶基因。TMEM182的降低，其對OSCC細胞的影響與miR-450a表現量上升是一致的。TMEM182在OSCC細胞內上升，對細胞呈現與miR-450a相反的結果。有趣的是，我們發現TNF-α降低TMEM182的表現是透過miR-450a的調控。然而恢復TMEM182於細胞內的表現，會阻斷miR-450a或TNF-α造成的細胞黏連能力的下降。更進一步,我們的研究發現TNF-α/miR-450a/TMEM182樞紐中，促使癌細胞移動的訊息是透過ERK1/2與NF-κB 傳遞。ERK1/2與NF-κB激酶抑制劑，有效的阻止TNF-α造成下降的細胞黏連。我們的研究指出，TNF-α活化ERK1/2與NF-κB去誘發miR-450a的表現來降低TMEM182的表現，最終促進OSCC細胞侵入能力提升。此途徑對腫瘤侵入佔一席重要的影響力。這結果提出由一嶄新的分子角度，去了解口腔癌惡化的過程。

Regardless of the well medical care system in Taiwan, the incidence rate of oral cancer has increased in years. Oral cancer metastasis is a critical issue which reduces the treatment outcome and causes the death. Recently, microRNA (miRNA) has been studied for its fine-tuning role in gene regulation and contributes to oral carcinogenesis. Previously, we found that there was a significantly upregulated hsa-mir-450a (miR-450a) in 35 clinical Oral Squamous Cell Carcinoma (OSCCs) specimens than those in corresponding adjacent normal (p<0.01). However, its function was unclear in oral cancer. Our purpose of this study was to unravel the function of miR-450a in OSCCs. MiR-450a expression was accessed with quantitative RT-PCR with OSCC cell lines and patients. We found that miR-450a impaired the OSCC attachment ability. Due to the fact that detachment of cancer cells is the initial step of cancer invasion, miR-450a increased cells invasion as well. Our results suggested that miR-450a acts as an onco-microRNA (oncomiR) in oral cancer progression. MicroRNA aligns the complementary site in the 3'UTR of target messenger RNA (mRNA) and silences its protein expression. We used gene microarray analysis to identify the target of miR-450a in OSCC cell lines, DOK and SAS. After in silico analysis, TMEM182 3'UTR luciferase expression, and TMEM182 protein expression, we found that TMEM182 was a putative target of miR-450a in OSCC. TMEM182-downregulated OSCCs mediated by shRNA plasmids decreased cell attachment ability, which was consistent with the function of miR-450a-overexpressed OSCCs. We further demonstrated that TMEM182 was located at intercellular connecting regions with green fluorescent protein-fused TMEM182 plasmids. MiR-450a-reduced cellular adhesion was recovered by TMEM182 addition. Moreover, we found that tumor necrosis factor alpha (TNF-α) induced miR-450a, and subsequent reduction of TMEM182. Using kinase inhibitors, we found that extracellular signal–regulated kinase 1/2 (ERK1/2) and nuclear factor NF-κB were involved in TNF-α-induced miR-450a regulation. Our findings provide a global story that miR-450a overexpression is important in facilitating OSCC tumor progression. In general, our data illustrated how a novel microRNA and a new adhesion protein promote oral carcinogenesis.

Titles                                                Page numbers

Chapter 1. Introduction
1.1.    Oral cancer........................................9
1.2.    MiRNA..............................................11
1.3.    MiR-450a...........................................13
1.4.    TMEM182............................................15
1.5.    TNF-α..............................................17
1.6.    Specific aims......................................19

Chapter 2. Materials and methods
2.1    Clinical human samples.............................20
2.2    Illumina array and microarray analysis.............20
2.3    Cell culture and transfection......................21
2.4    Cytokine and chemical inhibitors treatment.........22
2.5    RNA extraction and reverse-transcription PCR (RT-
PCR)........................                    ...22
2.6    Quantitative real-time PCR (qPCR)..................23
2.7    Plasmids...........................................23
2.8    Protein extraction and Western blot................25
2.9    Microscopic examination and Immunofluorescence
staining...........................................25
2.10    Adhesion and invasion assay.......................26
2.11    Luciferase reporter assay.........................27
2.12    Statistical analysis..............................28

Chapter 3. Results
3.1     Up-regulated miR-450a impairs cell adhesion ability, but
increases OSCC invasion...........................28
3.2     TMEM182 is down-regulated by miR-450a.............30
3.3     TMEM182 increases cell adhesion, but decreases
OSCC cell invasion ability........................31
3.4     TMEM182 makes OSCC cells resist to miR-450a
influence on cells................................32
3.5     TMEM182 is mediated by miR-450a in response to TNF-
α.................................................33
3.6     TNF-α activates ERK and NFκB pathways to induce
miR-450a expression...............................33

Chapter 4. Conclusion and future perspectives
4.1     Summary and discussion............................34
4.2     Perpectives and further research
4.2.1   Searching for intracellular mechanism of TMEM18...41
4.2.2   Larger statistics, better understanding about
miR-450a and TMEM182 at early-onset of oral cancer42
4.2.3  Besides TMEM182, the role of miR-450a in OSCC......43

Chapter 5. Reference......................................44

Chapter 6. Figures
Figure 1. Evolutionary conserved miR-450a in
primates................................54
Figure 2. Hydrophobic region prediction of
TMEM182.................................55
Figure 3. MiR-450a is up-regulated in OSCC........56
Figure 4. Overexpressed miR-450a reduces cell
adhesion ability........................57
Figure 5. MiR-450a enhances OSCC invasion ability.58
Figure 6. Kaplan-Meier survival plots of miR-450a.59
Figure 7. TMEM182 is a target of miR-450a in oral
cancer..................................60
Figure 8. MiR-450a regulates TMEM182 in
posttranslational level.................61
Figure 9. TMEM182 is down-regulated in clinical
specimens...............................62
Figure 10. TMEM182 knock-down decreases cell
adhesion ability........................63
Figure 11. Overexpressed TMEM182 impairs cell
motility................................64
Figure 12. Restoration of TMEM182 rescues
miR-450a effect on OSCC.................65
Figure 13. Invasion assay of TMEM182 recovers the
influence of miR-450a...................66
Figure 14. Fluorescence images of TMEM182 in OSCC
cells...................................67
Figure 15. TNF-α induces miR-450a expression, but
decreases TMEM182 expression............69
Figure 16. TNF-α represses TMEM182 through miR-
450a....................................70
Figure 17. Invasion assay of TMEM182 rescues TNF-α
effect..................................71
Figure 18. TNF-α induces miR-450a via ERK and
NFκB....................................72
Figure 19. ERK and NFκB inhibitors abolish TNF-α
effect on cells.........................73
Figure 20. ERK directly induces miR-450a to suppress
TMEM182.................................74
Figure 21. Effects of ERK and NFκB pathways on TNF-
α.......................................75
Figure 22. TNF-α activates miR-450a to mediate
TMEM182 expression......................76
Figure 23. Cellular locations analysis of
downregulated 256 common genes..........77
Table 1. Patients’ clinicopathological analysis...78
Table 2. Twelve of candidate genes are
downregulated by miR-450a................79
Table 3. Gene enriched analysis of KEGG pathways..80

                                

1. Zeljic, K., et al., MicroRNA meta-signature of oral cancer: evidence from a meta-analysis. Ups J Med Sci, 2018. 123(1): p. 43-49.
2. Su, C.C., et al., Distinctive features of oral cancer in Changhua County: high incidence, buccal mucosa preponderance, and a close relation to betel quid chewing habit. J Formos Med Assoc, 2007. 106(3): p. 225-33.
3. Jemal, A., et al., Cancer statistics, 2010. CA Cancer J Clin, 2010. 60(5): p. 277-300.
4. Friedlander, P.L., et al., Squamous cell carcinoma of the tongue in young patients: a matched-pair analysis. Head Neck, 1998. 20(5): p. 363-8.
5. Chuang, S.L., et al., Population-based screening program for reducing oral cancer mortality in 2,334,299 Taiwanese cigarette smokers and/or betel quid chewers. Cancer, 2017. 123(9): p. 1597-1609.
6. Goertzen, C., et al., Oral inflammation promotes oral squamous cell carcinoma invasion. Oncotarget, 2018. 9(49): p. 29047-29063.
7. Jerjes, W., et al., Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head Neck Oncol, 2010. 2: p. 9.
8. Stucky, A., et al., Single-cell genomic analysis of head and neck squamous cell carcinoma. Oncotarget, 2017. 8(42): p. 73208-73218.
9. Leemans, C.R., B.J. Braakhuis, and R.H. Brakenhoff, The molecular biology of head and neck cancer. Nat Rev Cancer, 2011. 11(1): p. 9-22.
10. Wang, B., et al., The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases. Chin J Cancer, 2013. 32(11): p. 614-8.
11. Mohan, S.P., et al., Immunotherapy in Oral Cancer. J Pharm Bioallied Sci, 2019. 11(Suppl 2): p. S107-s111.
12. Gomes, C.C. and R.S. Gomez, MicroRNA and oral cancer: future perspectives. Oral Oncol, 2008. 44(10): p. 910-4.
13. Manikandan, M., et al., Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism. Mol Cancer, 2016. 15: p. 28.
14. Fukumoto, I., et al., MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways. Br J Cancer, 2015. 112(5): p. 891-900.
15. Ries, J., et al., miR-186, miR-3651 and miR-494: potential biomarkers for oral squamous cell carcinoma extracted from whole blood. Oncol Rep, 2014. 31(3): p. 1429-36.
16. Yoon, A.J., et al., Prognostic value of miR-375 and miR-214-3p in early stage oral squamous cell carcinoma. Am J Transl Res, 2014. 6(5): p. 580-92.
17. Yoshizawa, J.M. and D.T. Wong, Salivary microRNAs and oral cancer detection. Methods Mol Biol, 2013. 936: p. 313-24.
18. Schneider, A., et al., Tissue and serum microRNA profile of oral squamous cell carcinoma patients. Sci Rep, 2018. 8(1): p. 675.
19. Yan, Y., et al., Circulating miRNAs as biomarkers for oral squamous cell carcinoma recurrence in operated patients. Oncotarget, 2017. 8(5): p. 8206-8214.
20. Shiah, S.G., Y.S. Shieh, and J.Y. Chang, The Role of Wnt Signaling in Squamous Cell Carcinoma. J Dent Res, 2016. 95(2): p. 129-34.
21. Kozaki, K., et al., Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res, 2008. 68(7): p. 2094-105.
22. Londin, E., et al., Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. Proc Natl Acad Sci U S A, 2015. 112(10): p. E1106-15.
23. Artzi, S., A. Kiezun, and N. Shomron, miRNAminer: a tool for homologous microRNA gene search. BMC Bioinformatics, 2008. 9: p. 39.
24. Tu, H.F., et al., Upregulation of miR-372 and -373 associates with lymph node metastasis and poor prognosis of oral carcinomas. Laryngoscope, 2015.
25. Baba, O., et al., MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis. J Oral Pathol Med, 2015.
26. Wienholds, E. and R.H. Plasterk, MicroRNA function in animal development. FEBS Lett, 2005. 579(26): p. 5911-22.
27. Rossi, S., et al., Cancer-associated genomic regions (CAGRs) and noncoding RNAs: bioinformatics and therapeutic implications. Mamm Genome, 2008. 19(7-8): p. 526-40.
28. Peng, H.Y., et al., IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma. Mol Oncol, 2016. 10(6): p. 895-909.
29. Bayraktar, R., K. Van Roosbroeck, and G.A. Calin, Cell-to-cell communication: microRNAs as hormones. Mol Oncol, 2017. 11(12): p. 1673-1686.
30. Shiah, S.G., et al., Downregulated miR329 and miR410 promote the proliferation and invasion of oral squamous cell carcinoma by targeting Wnt-7b. Cancer Res, 2014. 74(24): p. 7560-72.
31. Luo, J., et al., MicroRNA duplication accelerates the recruitment of new targets during vertebrate evolution. Rna, 2018. 24(6): p. 787-802.
32. Pinheiro, I., L. Dejager, and C. Libert, X-chromosome-located microRNAs in immunity: might they explain male/female differences? The X chromosome-genomic context may affect X-located miRNAs and downstream signaling, thereby contributing to the enhanced immune response of females. Bioessays, 2011. 33(11): p. 791-802.
33. Bianchi, I., et al., The X chromosome and immune associated genes. J Autoimmun, 2012. 38(2-3): p. J187-92.
34. Devor, E.J., et al., The miR-503 cluster is coordinately under-expressed in endometrial endometrioid adenocarcinoma and targets many oncogenes, cell cycle genes, DNA repair genes and chemotherapy response genes. Onco Targets Ther, 2018. 11: p. 7205-7211.
35. Jenkins, R.H., et al., miR-192 induces G2/M growth arrest in aristolochic acid nephropathy. Am J Pathol, 2014. 184(4): p. 996-1009.
36. Mouillet, J.F., et al., The unique expression and function of miR-424 in human placental trophoblasts. Biol Reprod, 2013. 89(2): p. 25.
37. Castellano, L., et al., The estrogen receptor-α-induced microRNA signature regulates itself and its transcriptional response. Proceedings of the National Academy of Sciences, 2009. 106(37): p. 15732-15737.
38. Huang, F., et al., Identification of potential diagnostic biomarkers for pneumonia caused by adenovirus infection in children by screening serum exosomal microRNAs. Mol Med Rep, 2019. 19(5): p. 4306-4314.
39. Lyu, L., et al., Small RNA Profiles of Serum Exosomes Derived From Individuals With Latent and Active Tuberculosis. Front Microbiol, 2019. 10: p. 1174.
40. Muys, B.R., et al., miR-450a acts as a tumor suppressor in ovarian cancer by regulating energy metabolism. Cancer Research, 2019: p. canres.0490.2019.
41. Zhu, Y., et al., miR-125b-5p and miR-99a-5p downregulate human gammadelta T-cell activation and cytotoxicity. Cell Mol Immunol, 2019. 16(2): p. 112-125.
42. Zhou, R.S., et al., Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue. BMC Cancer, 2019. 19(1): p. 779.
43. Weng, Z., et al., microRNA-450a targets DNA methyltransferase 3a in hepatocellular carcinoma. Exp Ther Med, 2011. 2(5): p. 951-955.
44. Liu, F., et al., Upregulation of microRNA-450 inhibits the progression of lung cancer in vitro and in vivo by targeting interferon regulatory factor 2. Int J Mol Med, 2016. 38(1): p. 283-90.
45. Zhang, Y., et al., Integrated transcriptome analysis reveals miRNA-mRNA crosstalk in laryngeal squamous cell carcinoma. Genomics, 2014. 104(4): p. 249-56.
46. Baffa, R., et al., MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol, 2009. 219(2): p. 214-21.
47. Castilla, M.A., et al., Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma. J Pathol, 2011. 223(1): p. 72-80.
48. Almeida, R.S., et al., MicroRNA expression profiles discriminate childhood T- from B-acute lymphoblastic leukemia. Hematol Oncol, 2019. 37(1): p. 103-112.
49. Wrzesinski, T., et al., Expression of pre-selected TMEMs with predicted ER localization as potential classifiers of ccRCC tumors. BMC Cancer, 2015. 15: p. 518.
50. Cheng, Z., et al., Overexpression of TMEM158 contributes to ovarian carcinogenesis. J Exp Clin Cancer Res, 2015. 34: p. 75.
51. Matsuba, S., et al., Downregulation of Ca2+-activated Cl- channel TMEM16A by the inhibition of histone deacetylase in TMEM16A-expressing cancer cells. J Pharmacol Exp Ther, 2014. 351(3): p. 510-8.
52. Qin, Y., et al., The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas and modulates endolysosomal function. Hum Mol Genet, 2014. 23(9): p. 2428-39.
53. Zhao, L.C., et al., TMEM45B promotes proliferation, invasion and migration and inhibits apoptosis in pancreatic cancer cells. Mol Biosyst, 2016. 12(6): p. 1860-70.
54. Kuninger, D., et al., Gene discovery by microarray: identification of novel genes induced during growth factor-mediated muscle cell survival and differentiation. Genomics, 2004. 84(5): p. 876-89.
55. Shi, D., et al., Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population. PLoS One, 2013. 8(1): p. e54115.
56. Wales, S., et al., Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling. Nucleic Acids Res, 2014. 42(18): p. 11349-62.
57. Wu, Y. and C.M. Smas, Expression and regulation of transcript for the novel transmembrane protein Tmem182 in the adipocyte and muscle lineage. BMC Res Notes, 2008. 1: p. 85.
58. Greuber, E.K., et al., Role of ABL family kinases in cancer: from leukaemia to solid tumours. Nat Rev Cancer, 2013. 13(8): p. 559-71.
59. Chuang, Y.C., et al., Molecular Modeling of ALK L1198F and/or G1202R Mutations to Determine Differential Crizotinib Sensitivity. Sci Rep, 2019. 9(1): p. 11390.
60. De Donato, M., et al., Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6. Sci Rep, 2018. 8(1): p. 16047.
61. Sigismund, S., D. Avanzato, and L. Lanzetti, Emerging functions of the EGFR in cancer. Mol Oncol, 2018. 12(1): p. 3-20.
62. Gehne, N., R.F. Haseloff, and I.E. Blasig, Identity crisis in the PMP-22/EMP/MP20/Claudin superfamily (Pfam00822). Tissue Barriers, 2015. 3(4): p. e1089680.
63. Heiskala, M., P.A. Peterson, and Y. Yang, The roles of claudin superfamily proteins in paracellular transport. Traffic, 2001. 2(2): p. 93-8.
64. Krause, G., et al., Structure and function of claudins. Biochim Biophys Acta, 2008. 1778(3): p. 631-45.
65. Rosenthal, R., et al., Claudin-2, a component of the tight junction, forms a paracellular water channel. Journal of Cell Science, 2010. 123(11): p. 1913.
66. Paquet-Fifield, S., et al., Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells. Cancer Res, 2018. 78(11): p. 2925-2938.
67. Tabaries, S., et al., Afadin cooperates with Claudin-2 to promote breast cancer metastasis. Genes Dev, 2019. 33(3-4): p. 180-193.
68. G, D., S.R.K. Nandan, and P.G. Kulkarni, Salivary Tumour Necrosis Factor-alpha as a Biomarker in Oral Leukoplakia and Oral Squamous Cell Carcinoma. Asian Pac J Cancer Prev, 2019. 20(7): p. 2087-2093.
69. Sahibzada, H.A., et al., Salivary IL-8, IL-6 and TNF-alpha as Potential Diagnostic Biomarkers for Oral Cancer. Diagnostics (Basel), 2017. 7(2).
70. Scheff, N.N., et al., Tumor necrosis factor alpha secreted from oral squamous cell carcinoma contributes to cancer pain and associated inflammation. Pain, 2017. 158(12): p. 2396-2409.
71. Ameena, M. and R. Rathy, Evaluation of tumor necrosis factor: Alpha in the saliva of oral cancer, leukoplakia, and healthy controls – A comparative study. Journal of International Oral Health, 2019. 11(2): p. 92-99.
72. Tang, D., et al., TNF-Alpha Promotes Invasion and Metastasis via NF-Kappa B Pathway in Oral Squamous Cell Carcinoma. Med Sci Monit Basic Res, 2017. 23: p. 141-149.
73. Yan, M., et al., [Inflammatory factors promote oral squamous cell carcinoma cells metastasis, via nuclear factor kappa B signal pathway in vitro]. Zhonghua Kou Qiang Yi Xue Za Zhi, 2010. 45(3): p. 146-51.
74. Furuta, H., et al., Selective inhibition of NF-kappaB suppresses bone invasion by oral squamous cell carcinoma in vivo. Int J Cancer, 2012. 131(5): p. E625-35.
75. Wu, J., et al., MicroRNA Roles in the Nuclear Factor Kappa B Signaling Pathway in Cancer. Front Immunol, 2018. 9: p. 546.
76. Zhao, X.W., et al., The role of MAPK signaling pathway in formation of EMT in oral squamous carcinoma cells induced by TNF-alpha. Mol Biol Rep, 2019. 46(3): p. 3149-3156.
77. Ding, J., D. Sun, and P. Xie, Elevated microRNA-145 inhibits the development of oral squamous cell carcinoma through inactivating ERK/MAPK signaling pathway by down-regulating HOXA1. Biosci Rep, 2019. 39(6).
78. Zhang, D., C. Lu, and H. Ai, Rab5a is overexpressed in oral cancer and promotes invasion through ERK/MMP signaling. Mol Med Rep, 2017. 16(4): p. 4569-4576.
79. Bu, W., et al., Disulfiram inhibits epithelial-mesenchymal transition through TGFbeta-ERK-Snail pathway independently of Smad4 to decrease oral squamous cell carcinoma metastasis. Cancer Manag Res, 2019. 11: p. 3887-3898.
80. Aggarwal, S., et al., Contrasting effects of ERK on tight junction integrity in differentiated and under-differentiated Caco-2 cell monolayers. Biochem J, 2011. 433(1): p. 51-63.
81. Bhat, A.A., et al., Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk. Front Physiol, 2018. 9: p. 1942.
82. Amoozadeh, Y., et al., Tumor necrosis factor-alpha induces a biphasic change in claudin-2 expression in tubular epithelial cells: role in barrier functions. Am J Physiol Cell Physiol, 2015. 309(1): p. C38-50.
83. Ziober, B.L., S.S. Silverman, Jr., and R.H. Kramer, Adhesive mechanisms regulating invasion and metastasis in oral cancer. Crit Rev Oral Biol Med, 2001. 12(6): p. 499-510.
84. Ramos Gde, O., et al., Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma. PLoS One, 2016. 11(3): p. e0151338.
85. Kamarajan, P., et al., The CS1 segment of fibronectin is involved in human OSCC pathogenesis by mediating OSCC cell spreading, migration, and invasion. BMC Cancer, 2010. 10: p. 330.
86. Kalliolias, G.D. and L.B. Ivashkiv, TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol, 2016. 12(1): p. 49-62.
87. Kim, J., et al., MicroRNAs and metastasis: small RNAs play big roles. Cancer Metastasis Rev, 2018. 37(1): p. 5-15.
88. Dernowsek, J.A., et al., Posttranscriptional Interaction Between miR-450a-5p and miR-28-5p and STAT1 mRNA Triggers Osteoblastic Differentiation of Human Mesenchymal Stem Cells. J Cell Biochem, 2017. 118(11): p. 4045-4062.
89. Koperski, L., et al., Next-generation sequencing reveals microRNA markers of adrenocortical tumors malignancy. Oncotarget, 2017. 8(30): p. 49191-49200.
90. Lv, Y., et al., Bioinformatics facilitating the use of microarrays to delineate potential miRNA biomarkers in aristolochic acid nephropathy. Oncotarget, 2016. 7(32): p. 52270-52280.
91. Delic, D., et al., Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats. Int J Mol Sci, 2016. 17(5).
92. Turksen, K. and T.C. Troy, Junctions gone bad: claudins and loss of the barrier in cancer. Biochim Biophys Acta, 2011. 1816(1): p. 73-9.
93. Heerboth, S., et al., EMT and tumor metastasis. Clin Transl Med, 2015. 4: p. 6.
94. Phattarataratip, E. and K. Sappayatosok, Expression of claudin-5, claudin-7 and occludin in oral squamous cell carcinoma and their clinico-pathological significance. J Clin Exp Dent, 2016. 8(3): p. e299-306.
95. Sappayatosok, K. and E. Phattarataratip, Overexpression of Claudin-1 is Associated with Advanced Clinical Stage and Invasive Pathologic Characteristics of Oral Squamous Cell Carcinoma. Head Neck Pathol, 2015. 9(2): p. 173-80.
96. Oku, N., et al., Tight junction protein claudin-1 enhances the invasive activity of oral squamous cell carcinoma cells by promoting cleavage of laminin-5 gamma2 chain via matrix metalloproteinase (MMP)-2 and membrane-type MMP-1. Cancer Res, 2006. 66(10): p. 5251-7.
97. Yoshizawa, K., et al., Loss of claudin-7 is a negative prognostic factor for invasion and metastasis in oral squamous cell carcinoma. Oncol Rep, 2013. 29(2): p. 445-50.
98. Bello, I.O., et al., Expression of claudins 1, 4, 5, and 7 and occludin, and relationship with prognosis in squamous cell carcinoma of the tongue. Hum Pathol, 2008. 39(8): p. 1212-20.
99. Venugopal, S., S. Anwer, and K. Szaszi, Claudin-2: Roles beyond Permeability Functions. Int J Mol Sci, 2019. 20(22).
100. Ghosh, S., et al., Loss of adhesion-regulated proteinase production is correlated with invasive activity in oral squamous cell carcinoma. Cancer, 2002. 95(12): p. 2524-33.
101. Lyons, A.J. and J. Jones, Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. Int J Oral Maxillofac Surg, 2007. 36(8): p. 671-9.
102. Jiang, R., et al., Kallikrein-5 promotes cleavage of desmoglein-1 and loss of cell-cell cohesion in oral squamous cell carcinoma. J Biol Chem, 2011. 286(11): p. 9127-35.
103. Lourenco, S.V., et al., Oral squamous cell carcinoma: status of tight junction claudins in the different histopathological patterns and relationship with clinical parameters. A tissue-microarray-based study of 136 cases. J Clin Pathol, 2010. 63(7): p. 609-14.
104. Ding, L., et al., The claudin family of proteins in human malignancy: a clinical perspective. Cancer Manag Res, 2013. 5: p. 367-75.
105. Shin, K., V.C. Fogg, and B. Margolis, Tight junctions and cell polarity. Annu Rev Cell Dev Biol, 2006. 22: p. 207-35.
106. Singh, A.B. and P. Dhawan, Claudins and cancer: Fall of the soldiers entrusted to protect the gate and keep the barrier intact. Semin Cell Dev Biol, 2015. 42: p. 58-65.
107. Thomas, G.J. and P.M. Speight, Cell adhesion molecules and oral cancer. Crit Rev Oral Biol Med, 2001. 12(6): p. 479-98.
108. Brockmeyer, P., et al., Membrane connexin 43 acts as an independent prognostic marker in oral squamous cell carcinoma. Int J Oncol, 2014. 45(1): p. 273-81.
109. Lee, L.T., et al., Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma. Int J Oral Maxillofac Surg, 2018. 47(6): p. 699-707.
110. Salazar, C., et al., A novel saliva-based microRNA biomarker panel to detect head and neck cancers. Cell Oncol (Dordr), 2014. 37(5): p. 331-8.
111. Xie, Z., et al., Salivary microRNAs as promising biomarkers for detection of esophageal cancer. PLoS One, 2013. 8(4): p. e57502.
112. Takamune, Y., et al., Involvement of NF-kappaB-mediated maturation of ADAM-17 in the invasion of oral squamous cell carcinoma. Biochem Biophys Res Commun, 2008. 365(2): p. 393-8.
113. Krishnan, R., et al., Association of serum and salivary tumor necrosis factor-alpha with histological grading in oral cancer and its role in differentiating premalignant and malignant oral disease. Asian Pac J Cancer Prev, 2014. 15(17): p. 7141-8.
114. Zhou, J.P., et al., Snail interacts with Id2 in the regulation of TNF-alpha-induced cancer cell invasion and migration in OSCC. Am J Cancer Res, 2015. 5(5): p. 1680-91.
115. Wu, Y. and B.P. Zhou, TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion. Br J Cancer, 2010. 102(4): p. 639-44.
116. Yu, T., et al., CXCR4 promotes oral squamous cell carcinoma migration and invasion through inducing expression of MMP-9 and MMP-13 via the ERK signaling pathway. Mol Cancer Res, 2011. 9(2): p. 161-72.
117. Ou, B., et al., CCR4 promotes metastasis via ERK/NF-kappaB/MMP13 pathway and acts downstream of TNF-alpha in colorectal cancer. Oncotarget, 2016.
118. Ghoda, L., X. Lin, and W.C. Greene, The 90-kDa ribosomal S6 kinase (pp90rsk) phosphorylates the N-terminal regulatory domain of IkappaBalpha and stimulates its degradation in vitro. J Biol Chem, 1997. 272(34): p. 21281-8.
119. Van Itallie, C.M., et al., Phosphorylation of claudin-2 on serine 208 promotes membrane retention and reduces trafficking to lysosomes. J Cell Sci, 2012. 125(Pt 20): p. 4902-12.
120. Capaldo, C.T., et al., Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins. Mol Biol Cell, 2014. 25(18): p. 2710-9.
121. Kakiashvili, E., et al., GEF-H1 mediates tumor necrosis factor-alpha-induced Rho activation and myosin phosphorylation: role in the regulation of tubular paracellular permeability. J Biol Chem, 2009. 284(17): p. 11454-66.
122. Akizuki, R., et al., Decrease in paracellular permeability and chemosensitivity to doxorubicin by claudin-1 in spheroid culture models of human lung adenocarcinoma A549 cells. Biochim Biophys Acta Mol Cell Res, 2018. 1865(5): p. 769-780.
123. Garavello, W., et al., Family history and the risk of oral and pharyngeal cancer. Int J Cancer, 2008. 122(8): p. 1827-31.
124. Chandler, K. and R. Goldman, Glycoprotein disease markers and single protein-omics. Mol Cell Proteomics, 2013. 12(4): p. 836-45.
125. Chen, J.T., et al., Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and immune response. Proc Natl Acad Sci U S A, 2015. 112(42): p. 13057-62.
126. Jang, J.Y., et al., The role of mitochondria in aging. J Clin Invest, 2018. 128(9): p. 3662-3670.
127. Porporato, P.E., et al., Mitochondrial metabolism and cancer. Cell Res, 2018. 28(3): p. 265-280.
128. Lemire, J., R.J. Mailloux, and V.D. Appanna, Mitochondrial lactate dehydrogenase is involved in oxidative-energy metabolism in human astrocytoma cells (CCF-STTG1). PLoS One, 2008. 3(2): p. e1550.
129. Jacobs, R.A., et al., Lactate oxidation in human skeletal muscle mitochondria. Am J Physiol Endocrinol Metab, 2013. 304(7): p. E686-94.

簡易檢索 / 詳目顯示

相關論文