SATB2 augments ΔNp63α in head and neck squamous cell carcinoma

Chung, Joon; Lau, Joanne; Cheng, Lynn S.; Grant, Ron; Robinson, Fiona; Ketela, Troy; Reis, Patrícia P.; Roche, Olga; Kamel‐Reid, Suzanne; Moffat, Jason; Ohh, Michael; Perez-Ordoñez, Bayardo; Kaplan, David R.; Irwin, Meredith S.

doi:10.1038/embor.2010.125

Cited by 48 publications

(52 citation statements)

References 17 publications

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“…Studies revealed that miR-519A was downregulated by ΔNp63α in cancers (48), and overexpression of ΔNp63α was beneficial for HNSCC resistance to chemotherapy-induced cell death via inhibiting the transcription of TAp73b (49). One study found that the downregulation of ΔNp63α was a determinant of cellular response to DNA damage in HNSCC (50).…”

Section: Discussionmentioning

confidence: 99%

Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways

Zhang²,

Xia

et al. 2015

Oncology Reports

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Abstract. The aim of the present study was to explore the potential mechanisms involved in each subtype of head and neck squamous cell carcinoma (HNSCC) via subpath analysis and to investigate their relevance in the prevention of HNSCC. Gene expression profiles of GSE6631 and GSE39366 containing 44 and 168 HNSCC samples, respectively, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from samples in GSE6631 and GSE393666 were screened using the Detection of Imbalanced Differential Signal (DIDS) method respectively. DEGs in GSE39366 were matched with the DEGs in GSE6631 and were used to classify the subtypes of HNSCC based on hierarchical clustering analysis. Furthermore, DEGs were separated into different subtypes and then the pathway information was analyzed. The regulated miRNAs for the DEGs in each subtype were analyzed to select the significant subpaths. Totally, 1,095 DEGs from GSE6631 and 2,528 DEGs from GSE39366 were screened. Samples in GSE39366 were separated into four subtypes. Specific genes in each subtype and DEGs in the common gene set involved in a variety of pathways were identified. In addition, the significant miRNAtarget-pathway subpath of each subtype of HNSCC and the common gene set of HNSCC were also enriched. Our data suggest that human papillomavirus (HPV) is positively correlated with HNSCC in subtype 2. Several miRNAs (miRLet-7A, miR-1, miR-206, miR-153, miR-519A and miR-506) and their target genes (CYP46A1, BPNT1, MCM7 and COL5A1) are crucial for HNSCC prevention via different pathways and may provide further knowledge of the mechanisms involved in the progression of HNSCC.

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Section: Discussionmentioning

confidence: 99%

Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways

Zhang²,

Xia

et al. 2015

Oncology Reports

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“…Transfections and Lentivirus Infections-HEK293 and H1299 cells were transfected using calcium phosphate and polyethylenimine methods, respectively, as described previously (26). NIH 3T3 cells were transiently transfected using FuGENE6 transfection reagent (Roche Applied Science) according to the manufacturer's instructions.…”

Section: Hematoxylin and Eosin Staining-p63mentioning

confidence: 99%

“…Plasmids encoding wild-type TA and ⌬Np63␣ as well as T7-SATB2 have been described previously (26). AEC-and EEC-associated p63␣ mutants were generated using a QuikChange Site-directed Mutagenesis kit (Stratagene) according to the manufacturer's instructions.…”

Section: Hematoxylin and Eosin Staining-p63mentioning

confidence: 99%

“…NIH 3T3 cells were transiently transfected using FuGENE6 transfection reagent (Roche Applied Science) according to the manufacturer's instructions. Production of lentivirus-expressing shGFP and two different shRNAs targeting SATB2 as well as infection of SCC9 cells were performed as described previously (26).…”

Section: Hematoxylin and Eosin Staining-p63mentioning

confidence: 99%

“…In addition, satb2 Ϫ/Ϫ mice and humans with loss-of-function satb2 mutations develop craniofacial abnormalities including orofacial clefting (22)(23)(24)(25). Previously, we have shown that SATB2 and ⌬Np63␣ form an endogenous molecular complex in vivo, regulating proapoptotic target gene transcriptional activation and survival of cancer cells (26). Here, we show that unlike EEC TAp63␣, AEC TAp63␣-mediated transactivation function is inhibited by SATB2 and specifically attenuates the transactivation of perp, a gene involved in ectodermal development (10).…”

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confidence: 99%

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Special AT-rich Binding Protein-2 (SATB2) Differentially Affects Disease-causing p63 Mutant Proteins

Chung

Grant

Kaplan

et al. 2011

Journal of Biological Chemistry

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p63, a p53 family member, is critical for proper skin and limb development and directly regulates gene expression in the ectoderm. Mice lacking p63 exhibit skin and craniofacial defects including cleft palate. In humans p63 mutations are associated with several distinct developmental syndromes. p63 sterile-␣-motif domain, AEC (ankyloblepharon-ectodermal dysplasiaclefting)-associated mutations are associated with a high prevalence of orofacial clefting disorders, which are less common in EEC (ectrodactyly-ectodermal dysplasia-clefting) patients with DNA binding domain p63 mutations. However, the mechanisms by which these mutations differentially influence p63 function remain unclear, and interactions with other proteins implicated in craniofacial development have not been identified. Here, we show that AEC p63 mutations affect the ability of the p63 protein to interact with special AT-rich binding protein-2 (SATB2), which has recently also been implicated in the development of cleft palate. p63 and SATB2 are co-expressed early in development in the ectoderm of the first and second branchial arches, two essential sites where signaling is required for craniofacial patterning. SATB2 attenuates p63-mediated gene expression of perp (p53 apoptosis effector related to PMP-22), a critical downstream target gene during development, and specifically decreases p63 perp promoter binding. Interestingly, AEC but not EEC p63 mutations affect the ability of p63 to interact with SATB2 and the inhibitory effects of SATB2 on p63 transactivation of perp are most pronounced for AEC-associated p63 mutations. Our findings reveal a novel gain-of-function property of AEC-causing p63 mutations and identify SATB2 as the first p63 binding partner that differentially influences AEC and EEC p63 mutant proteins.p63, a member of the p53 family of transcription factors, encodes multiple isoforms that arise from alternative splicing and transcription from two distinct promoters (1, 2). The latter mechanism generates transactivating (TA) 4 or dominant negative (⌬N) p63 proteins (1, 2). TAp63 proteins possess typical p53-like properties whereas ⌬Np63 are incapable of inducing characteristic p53 target genes and can also inhibit TAp53 family members (1, 2).In addition to inhibiting TAp53 family proteins, ⌬Np63 can also activate transcription of a distinct subset of genes, including integrin-␤4, dlx3/5/6, p57Kip2, and claudin-1 (3-7). These genes have been implicated in early embryonic patterning processes and ectodermal development. Consistent with these observations, p63Ϫ/Ϫ mice exhibit malformations in ectodermderived structures such as the skin and limbs that are not found in mice lacking the other p53 family members (8, 9). Furthermore, a majority of mice specifically lacking TAp63 die during embryonic development, and any remaining pups that are born exhibit multiple defects (3). A significant proportion of TAp63 Ϫ/Ϫ animals develop blisters and ulcerations due to impaired wound healing (3). Hair follicle defects and cysts were also detected in...

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MiR‐34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2

Gao

Sun

Wang

et al. 2019

Journal Cellular Physiology

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In various kinds of carcinomas, the special AT-rich sequence-binding protein 2 (SATB2) with its atypical expression promotes the metastasis and progression of the tumor, though in the oral squamous cell carcinoma (OSCC) its inherent mechanism and the status of SATB2 remain unclear. The role played by the SATB2 expression in the OSCC cell lines and tissue samples in the target of miR-34a downstream is the intended endeavor of this study. In te OSCCs the miR-34a expression was determined by quantitative real-time polymerase chain reaction (q-PCR), while the SATB2 expression in the cell lines and tissue samples in OSCC was analyzed with the q-PCR and the western blot. Studies in both in vitro and in vivo of the effects of miR-34a on the initiation of OSCC were conducted. As a direct target of the miR-34a the SATB2 was verified with the luciferase reporter assay. In cases where the miR-34a levels were low, the SATB2 in OSCCs seemed to be overexpressed. Besides, both in the in vitro and in vivo a suppression of migration, invasion, and cell growth was caused by miR-34a by down regulating the SATB2 expression. The SATB2 being a direct target of miR-34a was confirmed by the cotransfection of miR-34a mimics specifically the decrease in the expression of luciferase of SATB2-3′UTR-wt reporter.As a whole, our study confirmed the inhibition of miR-34a in the invasion, proliferation, and migration of the OSCCs, playing a potential tumor suppressor role with SATB2 as its downstream target.

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SATB2 augments ΔNp63α in head and neck squamous cell carcinoma

Cited by 48 publications

References 17 publications

Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways

Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways

Special AT-rich Binding Protein-2 (SATB2) Differentially Affects Disease-causing p63 Mutant Proteins

MiR‐34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2

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