Mediator complex subunit 1 promotes oral squamous cell carcinoma progression by activating MMP9 transcription and suppressing CD8
Humans
Mouth Neoplasms
/ pathology
CD8-Positive T-Lymphocytes
/ immunology
Mice
Animals
Matrix Metalloproteinase 9
/ metabolism
Disease Progression
Mediator Complex Subunit 1
/ metabolism
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Male
Female
Gene Expression Regulation, Neoplastic
Cell Proliferation
Prognosis
Matrix metalloprotein 9
Notch signaling pathway
Oral squamous cell carcinoma
Programmed death-ligand 1
The Mediator complex subunit 1
Transcriptional regulation
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
received:
06
06
2024
accepted:
13
09
2024
medline:
30
9
2024
pubmed:
30
9
2024
entrez:
29
9
2024
Statut:
epublish
Résumé
The role of Mediator complex subunit 1 (MED1), a pivotal transcriptional coactivator implicated in diverse biological pathways, remains unexplored in the context of oral squamous cell carcinoma (OSCC). This study aims to elucidate the contributory mechanisms and potential impact of MED1 on the progression of OSCC. The expression and clinical significance of MED1 in OSCC tissues were evaluated through the bioinformatics analyses. The effects of MED1 on the biological behavior of OSCC cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay, bioinformatic analysis, CD8 MED1 exhibited upregulation in both OSCC tissues and multiple OSCC cell lines, which correlated with decreased overall survival in patients. In vitro experiments demonstrated that knockdown of MED1 in metastatic OSCC cell lines SCC-9 and UPCI-SCC-154 hindered cell migration and invasion, while overexpression of MED1 promoted these processes. Whereas, MED1 knockdown had no impact on proliferation of cell lines mentioned above. In vivo studies further revealed that downregulation of MED1 effectively suppressed distant metastasis in OSCC. Mechanistically, MED1 enhanced the binding of transcription factors c-Jun and c-Fos to the matrix metalloprotein 9 (MMP9) promoters, resulting in a significant upregulation of MMP9 transcription. This process contributes to the migration and invasion of SCC-9 and UPCI-SCC-154 cells. Furthermore, MED1 modulated the expression of programmed death-ligand 1 (PD-L1) through the Notch signaling pathway, consequently impacting the tumor-killing capacity of CD8 Our findings indicate that MED1 plays a pivotal role in OSCC progression through the activation of MMP9 transcription and suppression of CD8
Sections du résumé
BACKGROUND
BACKGROUND
The role of Mediator complex subunit 1 (MED1), a pivotal transcriptional coactivator implicated in diverse biological pathways, remains unexplored in the context of oral squamous cell carcinoma (OSCC). This study aims to elucidate the contributory mechanisms and potential impact of MED1 on the progression of OSCC.
METHODS
METHODS
The expression and clinical significance of MED1 in OSCC tissues were evaluated through the bioinformatics analyses. The effects of MED1 on the biological behavior of OSCC cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay, bioinformatic analysis, CD8
RESULTS
RESULTS
MED1 exhibited upregulation in both OSCC tissues and multiple OSCC cell lines, which correlated with decreased overall survival in patients. In vitro experiments demonstrated that knockdown of MED1 in metastatic OSCC cell lines SCC-9 and UPCI-SCC-154 hindered cell migration and invasion, while overexpression of MED1 promoted these processes. Whereas, MED1 knockdown had no impact on proliferation of cell lines mentioned above. In vivo studies further revealed that downregulation of MED1 effectively suppressed distant metastasis in OSCC. Mechanistically, MED1 enhanced the binding of transcription factors c-Jun and c-Fos to the matrix metalloprotein 9 (MMP9) promoters, resulting in a significant upregulation of MMP9 transcription. This process contributes to the migration and invasion of SCC-9 and UPCI-SCC-154 cells. Furthermore, MED1 modulated the expression of programmed death-ligand 1 (PD-L1) through the Notch signaling pathway, consequently impacting the tumor-killing capacity of CD8
CONCLUSIONS
CONCLUSIONS
Our findings indicate that MED1 plays a pivotal role in OSCC progression through the activation of MMP9 transcription and suppression of CD8
Identifiants
pubmed: 39343952
doi: 10.1186/s13046-024-03191-9
pii: 10.1186/s13046-024-03191-9
doi:
Substances chimiques
Matrix Metalloproteinase 9
EC 3.4.24.35
MMP9 protein, human
EC 3.4.24.35
Mediator Complex Subunit 1
0
MED1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
270Informations de copyright
© 2024. The Author(s).
Références
Carnielli CM, Macedo CCS, De Rossi T, Granato DC, Rivera C, Domingues RR, et al. Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer. Nat Commun. 2018;9(1):3598.
Tan Y, Wang Z, Xu M, Li B, Huang Z, Qin S, et al. Oral squamous cell carcinomas: state of the field and emerging directions. Int J Oral Sci. 2023;15(1):44.
pubmed: 37736748
pmcid: 10517027
doi: 10.1038/s41368-023-00249-w
Peña-Oyarzún D, Reyes M, Hernández-Cáceres MP, Kretschmar C, Morselli E, Ramirez-Sarmiento CA, et al. Role of Autophagy in the Microenvironment of Oral Squamous Cell Carcinoma. Front Oncol. 2020;10:602661.
Chai AWY, Lim KP, Cheong SC. Translational genomics and recent advances in oral squamous cell carcinoma. Semin Cancer Biol. 2020;61:71–83.
pubmed: 31542510
doi: 10.1016/j.semcancer.2019.09.011
Sasahira T, Kirita T. Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma. Int J Mol Sci. 2018;19(8):2413.
Radaic A, Kamarajan P, Cho A, Wang S, Hung GC, Najarzadegan F, et al. Biological biomarkers of oral cancer. Periodontology 2000. 2023. https://doi.org/10.1111/prd.12542 .
Bradner JE, Hnisz D, Young RA. Transcriptional addiction in cancer. Cell. 2017;168(4):629–43.
pubmed: 28187285
pmcid: 5308559
doi: 10.1016/j.cell.2016.12.013
Ell B, Kang Y. Transcriptional control of cancer metastasis. Trends Cell Biol. 2013;23(12):603–11.
pubmed: 23838335
doi: 10.1016/j.tcb.2013.06.001
Richter WF, Nayak S, Iwasa J, Taatjes DJ. The mediator complex as a master regulator of transcription by RNA polymerase II. Nat Rev Mol Cell Biol. 2022;23(11):732–49.
pubmed: 35725906
pmcid: 9207880
doi: 10.1038/s41580-022-00498-3
Soutourina J. Transcription regulation by the mediator complex. Nat Rev Mol Cell Biol. 2018;19(4):262–74.
pubmed: 29209056
doi: 10.1038/nrm.2017.115
Borggrefe T, Yue X. Interactions between subunits of the Mmediator complex with gene-specific transcription factors. Semin Cell Dev Biol. 2011;22(7):759–68.
pubmed: 21839847
doi: 10.1016/j.semcdb.2011.07.022
Chen X, Yin X, Li J, Wu Z, Qi Y, Wang X, et al. Structures of the human Mediator and Mediator-bound preinitiation complex. Science. 2021;372(6546):eabg0635.
Spaeth JM, Kim NH, Boyer TG. Mediator and human disease. Semin Cell Dev Biol. 2011;22(7):776–87.
pubmed: 21840410
pmcid: 4100472
doi: 10.1016/j.semcdb.2011.07.024
Grueter CE. Mediator complex dependent regulation of cardiac development and disease. Genomics Proteomics Bioinformatics. 2013;11(3):151–7.
pubmed: 23727265
pmcid: 4357813
doi: 10.1016/j.gpb.2013.05.002
Schiano C, Casamassimi A, Rienzo M, de Nigris F, Sommese L, Napoli C. Involvement of mediator complex in malignancy. Biochim Biophys Acta. 2014;1845(1):66–83.
pubmed: 24342527
Jia Y, Viswakarma N, Reddy JK. Med1 subunit of the mediator complex in nuclear receptor-regulated energy metabolism, liver regeneration, and hepatocarcinogenesis. Gene Expr. 2014;16(2):63–75.
pubmed: 24801167
pmcid: 4093800
doi: 10.3727/105221614X13919976902219
Viswakarma N, Jia Y, Bai L, Gao Q, Lin B, Zhang X, et al. The Med1 subunit of the mediator complex induces liver cell proliferation and is phosphorylated by AMP kinase. J Biol Chem. 2013;288(39):27898–911.
pubmed: 23943624
pmcid: 3784705
doi: 10.1074/jbc.M113.486696
Slominski AT, Yoshizaki K, Hu L, Nguyen T, Sakai K, He B, et al. Ablation of Coactivator Med1 Switches the Cell Fate of Dental Epithelia to That Generating Hair. PLoS ONE. 2014;9(6):e99991.
Wei R, Guo S, Meng Z, Li Z, Liu J, Hu L, et al. Mediator1 involved in functional integration of Smad3 and Notch1 promoting enamel mineralization. Biochem Biophys Res Commun. 2023;663:47–53.
pubmed: 37119765
doi: 10.1016/j.bbrc.2023.04.053
Meng Z, Li Z, Guo S, Wu D, Wei R, Liu J, et al. MED1 Ablation Promotes Oral Mucosal Wound Healing via JNK Signaling Pathway. Int J Mol Sci. 2022;23(21):13414.
Cui J, Germer K, Wu T, Wang J, Luo J, Wang SC, et al. Cross-talk between HER2 and MED1 regulates tamoxifen resistance of human breast cancer cells. Cancer Res. 2012;72(21):5625–34.
pubmed: 22964581
pmcid: 4141533
doi: 10.1158/0008-5472.CAN-12-1305
Jin F, Claessens F, Fondell JD. Regulation of androgen receptor-dependent transcription by coactivator MED1 is mediated through a newly discovered noncanonical binding motif. J Biol Chem. 2012;287(2):858–70.
pubmed: 22102282
doi: 10.1074/jbc.M111.304519
Matsumoto K, Yu S, Jia Y, Ahmed MR, Viswakarma N, Sarkar J, et al. Critical role for transcription coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein/TRAP220 in liver regeneration and PPARalpha ligand-induced liver tumor development. J Biol Chem. 2007;282(23):17053–60.
pubmed: 17438330
doi: 10.1074/jbc.M701956200
Jiang C, Chen H, Shao L, Wang Q. MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31. Oncol Rep. 2014;32(3):1249–56.
pubmed: 24969180
doi: 10.3892/or.2014.3274
Howard JH, Frolov A, Tzeng CW, et al. Epigenetic downregulation of the DNA repair gene MED1/MBD4 in colorectal and ovarian cancer. Cancer Biol Ther. 2009;8(1):94–100.
pubmed: 19127118
doi: 10.4161/cbt.8.1.7469
Klumper N, Syring I, Vogel W, Schmidt D, Muller SC, Ellinger J, et al. Mediator complex subunit med1 protein expression is decreased during bladder cancer progression. Front Med (Lausanne). 2017;4:30.
pubmed: 28367434
doi: 10.3389/fmed.2017.00030
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.
pubmed: 21376230
doi: 10.1016/j.cell.2011.02.013
Casey SC, Baylot V, Felsher DW. MYC: master regulator of immune privilege. Trends Immunol. 2017;38(4):298–305.
pubmed: 28233639
pmcid: 5378645
doi: 10.1016/j.it.2017.01.002
Zhang Q, Wei F, Wang HY, Liu X, Roy D, Xiong Q-B, et al. The potent oncogene NPM-ALK mediates malignant transformation of normal human CD4+ T lymphocytes. Am J Pathol. 2013;183(6):1971–80.
pubmed: 24404580
pmcid: 5745542
doi: 10.1016/j.ajpath.2013.08.030
Seliger B, Massa C. Modulation of Lymphocyte Functions in the Microenvironment by Tumor Oncogenic Pathways. Front Immunol. 2022;13:883639.
Lin CJ, Grandis JR, Carey TE, Gollin SM, Whiteside TL, Koch WM, et al. Head and neck squamous cell carcinoma cell lines: stablished models and rationale for selection. Head Neck. 2006;29(2):163–88.
doi: 10.1002/hed.20478
Göttgens EL, Ansems M, Leenders WPJ, Bussink J, Span PN. Genotyping and characterization of HPV status, hypoxia, and radiosensitivity in 22 head and neck cancer cell lines. Cancers (Basel). 2021;13(5):1069.
pubmed: 33802339
doi: 10.3390/cancers13051069
de Almeida LGN, Thode H, Eslambolchi Y, Chopra S, Young D, Gill S, et al. Matrix metalloproteinases: from molecular mechanisms to physiology, pathophysiology, and pharmacology. Pharmacol Rev. 2022;74(3):714–70.
doi: 10.1124/pharmrev.121.000349
Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, et al. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2020;21(24):9739.
Mondal S, Adhikari N, Banerjee S, Amin SA, Jha T. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview. Eur J Med Chem. 2020;205:112642.
Lu L, Xue X, Lan J, Gao Y, Xiong Z, Zhang H, et al. MicroRNA-29a upregulates MMP2 in oral squamous cell carcinoma to promote cancer invasion and anti-apoptosis. Biomed Pharmacother. 2014;68(1):13–9.
pubmed: 24210072
doi: 10.1016/j.biopha.2013.10.005
Ruan S, Lin M, Zhu Y, Lum L, Thakur A, Jin R, et al. Integrin β4–targeted cancer immunotherapies inhibit tumor growth and decrease metastasis. Can Res. 2020;80(4):771–83.
doi: 10.1158/0008-5472.CAN-19-1145
Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T. Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem. 2003;253(1–2):269–85.
pubmed: 14619979
doi: 10.1023/A:1026028303196
Dolina JS, Van Braeckel-Budimir N, Thomas GD, Salek-Ardakani S. CD8+ T cell exhaustion in cancer. Front Immunol. 2021;12:715234.
Park J, Hsueh P-C, Li Z, Ho P-C. Microenvironment-driven metabolic adaptations guiding CD8+ T cell anti-tumor immunity. Immunity. 2023;56(1):32–42.
pubmed: 36630916
doi: 10.1016/j.immuni.2022.12.008
Mortezaee K, Majidpoor J. Mechanisms of CD8+ T cell exclusion and dysfunction in cancer resistance to anti-PD-(L)1. Biomed Pharmacother. 2023;163:114824.
Farhood B, Najafi M, Mortezaee K. CD8+ cytotoxic T lymphocytes in cancer immunotherapy: a review. J Cell Physiol. 2018;234(6):8509–21.
pubmed: 30520029
doi: 10.1002/jcp.27782
Tang E, Lahmi L, Meillan N, Pietta G, Albert S, Maingon P. Treatment Strategy for Distant Synchronous Metastatic Head and Neck Squamous Cell Carcinoma. Curr Oncol Rep. 2019;21(11):102.
Jeronimo C, Robert F. The mediator complex: at the nexus of RNA polymerase II transcription. Trends Cell Biol. 2017;27(10):765–83.
pubmed: 28778422
doi: 10.1016/j.tcb.2017.07.001
Rasool RU, Natesan R, Deng Q, Aras S, Lal P, Sander Effron S, et al. CDK7 inhibition suppresses castration-resistant prostate cancer through MED1 inactivation. Cancer Discov. 2019;9(11):1538–55.
pubmed: 31466944
doi: 10.1158/2159-8290.CD-19-0189
Chen Z, Ye Z, Soccio RE, Nakadai T, Hankey W, Zhao Y, et al. Phosphorylated MED1 links transcription recycling and cancer growth. Nucleic Acids Res. 2022;50(8):4450–63.
pubmed: 35394046
pmcid: 9071494
doi: 10.1093/nar/gkac246
Lee YL, Ito K, Pi WC, Lin IH, Chu CS, Malik S, et al. Mediator subunit MED1 is required for E2A-PBX1–mediated oncogenic transcription and leukemic cell growth. Proc Natl Acad Sci. 2021;118(6):e1922864118.
pubmed: 33542097
pmcid: 8017927
doi: 10.1073/pnas.1922864118
Jurado Acosta A, Rysä J, Szabo Z, Moilanen A-M, Komati H, Nemer M, et al. Transcription factor PEX1 modulates extracellular matrix turnover through regulation of MMP-9 expression. Cell Tissue Res. 2016;367(2):369–85.
pubmed: 27826738
doi: 10.1007/s00441-016-2527-2
Noll B, Mougeot FB, Brennan MT, Mougeot J-LC. Regulation of MMP9 transcription by ETS1 in immortalized salivary gland epithelial cells of patients with salivary hypofunction and primary Sjögren’s syndrome. Sci Rep. 2022;12(1):14552.
Vandooren J, Van den Steen PE, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade. Crit Rev Biochem Mol Biol. 2013;48(3):222–72.
pubmed: 23547785
doi: 10.3109/10409238.2013.770819
Zhao X, Benveniste EN. Transcriptional activation of human matrix metalloproteinase-9 gene expression by multiple co-activators. J Mol Biol. 2008;383(5):945–56.
pubmed: 18790699
pmcid: 2748421
doi: 10.1016/j.jmb.2008.08.071
Shin Y, Kim S, Ghate N, Rhie S, An WJO. MMP-9 drives the melanomagenic transcription program through histone H3 tail proteolysis. Oncogene. 2022;41(4):560–70.
pubmed: 34785776
doi: 10.1038/s41388-021-02109-5
Santer FR, Höschele PPS, Oh SJ, Erb HHH, Bouchal J, Cavarretta IT, et al. Inhibition of the acetyltransferases p300 and cbp reveals a targetable function for p300 in the survival and invasion pathways of prostate cancer cell lines. Mol Cancer Ther. 2011;10(9):1644–55.
pubmed: 21709130
doi: 10.1158/1535-7163.MCT-11-0182
El Messaoudi S, Fabbrizio E, Rodriguez C, et al. Coactivator-associated arginine methyltransferase 1 (CARM1) is a positive regulator of the Cyclin E1 gene. Proc Natl Acad Sci U S A. 2006;103(36):13351–6.
pubmed: 16938873
pmcid: 1569167
doi: 10.1073/pnas.0605692103
Hong H, Kao C, Jeng MH, Eble JN, Koch MO, Gardner TA, et al. Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status. Cancer. 2004;101(1):83–9.
pubmed: 15221992
doi: 10.1002/cncr.20327
Yuan H, Yu S, Cui Y, Men C, Yang D, Gao Z, et al. Knockdown of mediator subunit Med19 suppresses bladder cancer cell proliferation and migration by downregulating Wnt/β-catenin signalling pathway. J Cell Mol Med. 2017;21(12):3254–63.
pubmed: 28631286
pmcid: 5706513
doi: 10.1111/jcmm.13229
Sun K, Wang S, He J, et al. NCOA5 promotes proliferation, migration and invasion of colorectal cancer cells via activation of PI3K/AKT pathway. Oncotarget. 2017;8(64):107932–46.
pubmed: 29296214
pmcid: 5746116
doi: 10.18632/oncotarget.22429
Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2(3):161–74.
pubmed: 11990853
doi: 10.1038/nrc745
Zhang Q, Liu S, Wang H, Xiao K, Lu J, Chen S, et al. ETV4 mediated tumor-associated neutrophil infiltration facilitates lymphangiogenesis and lymphatic metastasis of bladder cancer. Adv Sci. 2023;10(11):e2205613.
Herszényi L, Hritz I, Lakatos G, Varga M, Tulassay Z. The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer. Int J Mol Sci. 2012;13(12):13240–63.
pubmed: 23202950
pmcid: 3497324
doi: 10.3390/ijms131013240
van der Leun AM, Thommen DS, Schumacher TN. CD8+ T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer. 2020;20(4):218–32.
pubmed: 32024970
pmcid: 7115982
doi: 10.1038/s41568-019-0235-4
Meurette O, Mehlen P. Notch Signaling in the Tumor Microenvironment. Cancer Cell. 2018;34(4):536–48.
pubmed: 30146333
doi: 10.1016/j.ccell.2018.07.009
Peng D, Tanikawa T, Li W, Zhao L, Vatan L, Szeliga W, et al. Myeloid-derived suppressor cells endow stem-like qualities to breast cancer cells through IL6/STAT3 and NO/NOTCH cross-talk signaling. Can Res. 2016;76(11):3156–65.
doi: 10.1158/0008-5472.CAN-15-2528
Otani Y, Yoo JY, Lewis CT, Chao S, Swanner J, Shimizu T, et al. NOTCH-induced MDSC Recruitment after oHSV virotherapy in cns cancer models modulates antitumor immunotherapy. Clin Cancer Res. 2022;28(7):1460–73.
pubmed: 35022322
pmcid: 8976724
doi: 10.1158/1078-0432.CCR-21-2347
Meng J, Jiang Y-z, Zhao S, Tao Y, Zhang T, Wang X, et al. Tumor-derived Jagged1 promotes cancer progression through immune evasion. Cell Reports. 2022;38(10):110492.
Petty AJ, Dai R, Lapalombella R, Baiocchi RA, Benson DM, Li Z, et al. Hedgehog-induced PD-L1 on tumor-associated macrophages is critical for suppression of tumor-infiltrating CD8+ T cell function. JCI Insight. 2021;6(6):e146707.
Wang JJ, Siu MK, Jiang YX, Leung TH, Chan DW, Cheng RR, et al. Aberrant upregulation of PDK1 in ovarian cancer cells impairs CD8+ T cell function and survival through elevation of PD-L1. OncoImmunology. 2019;8(11):e1659092.
Thibaudin M, Limagne E, Hampe L, Ballot E, Truntzer C, Ghiringhelli F. Targeting PD-L1 and TIGIT could restore intratumoral CD8 T cell function in human colorectal cancer. Cancer Immunol Immunother. 2022;71(10):2549–63.
pubmed: 35292828
pmcid: 10992601
doi: 10.1007/s00262-022-03182-9
Lei L, Yang X, Su Y, Zheng H, Liu J, Liu H, et al. Med1 controls CD8 T cell maintenance through IL-7R-mediated cell survival signalling. J Cell Mol Med. 2021;25(10):4870–6.
pubmed: 33733611
pmcid: 8107092
doi: 10.1111/jcmm.16465
Jiao A, Liu H, Ding R, Zheng H, Zhang C, Feng Z, et al. Med1 controls effector CD8+ T cell differentiation and survival through C/EBPβ-mediated transcriptional control of T-bet. J Immunol. 2022;209(5):855–63.
pubmed: 36130132
doi: 10.4049/jimmunol.2200037
Furukawa K, Kawasaki G, Yoshida T, Umeda M. Clinicopathological and prognostic analysis of PD-L1 and PD-L2 expression in surgically resected primary tongue squamous cell carcinoma. Anticancer Res. 2021;41(1):101–11.
pubmed: 33419803
doi: 10.21873/anticanres.14755
Ye Y, Kuang X, Xie Z, Liang L, Zhang Z, Zhang Y, et al. Small-molecule MMP2/MMP9 inhibitor SB-3CT modulates tumor immune surveillance by regulating PD-L1. Genom Med. 2020;12(1):83.
Pott S, Lieb JD. What are super-enhancers? Nat Genet. 2015;47(1):8–12.
pubmed: 25547603
doi: 10.1038/ng.3167
Dong J, Li J, Li Y, Ma Z, Yu Y, Wang CY. Transcriptional super-enhancers control cancer stemness and metastasis genes in squamous cell carcinoma. Nat Commun. 2021;12(1):3974.
pubmed: 34172737
pmcid: 8233332
doi: 10.1038/s41467-021-24137-1
Cai H, Liang J, Jiang Y, Wang Z, Li H, Wang W, et al. KLF7 regulates super-enhancer-driven IGF2BP2 overexpression to promote the progression of head and neck squamous cell carcinoma. J Exp Clin Cancer Res. 2024;43(1):69.
pubmed: 38443991
pmcid: 10913600
doi: 10.1186/s13046-024-02996-y
Bian E, Chen X, Cheng L, Cheng M, Chen Z, Yue X, et al. Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc. J Exp Clin Cancer Res. 2021;40(1):337.
pubmed: 34696771
pmcid: 8543865
doi: 10.1186/s13046-021-02129-9
Jung AR, Eun YG, Lee YC, Noh JK, Kwon KH. Clinical Significance of CUB and Sushi Multiple Domains 1 Inactivation in Head and Neck Squamous Cell Carcinoma. Int J Mol Sci. 2018;19(12):3996.
Baltaci E, Karaman E, Dalay N, Buyru N. Analysis of gene copy number changes in head and neck cancer. Clin Otolaryngol. 2018;43(4):1004–9.
pubmed: 27259694
doi: 10.1111/coa.12686
Khan AA, Patel K, Patil S, Babu N, Mangalaparthi KK, Solanki HS, et al. Multi-omics analysis to characterize cigarette smoke induced molecular alterations in esophageal cells. Front Oncol. 2020;10: 1666.
pubmed: 33251127
pmcid: 7675040
doi: 10.3389/fonc.2020.01666
Chen X, Kong D, Deng J, Mo F, Liang J. Overexpression of circFNDC3B promotes the progression of oral tongue squamous cell carcinoma through the miR-1322/MED1 axis. Head Neck. 2022;44(11):2417–27.
pubmed: 35916453
doi: 10.1002/hed.27152