TFAP2A Induced KRT16 as an Oncogene in Lung Adenocarcinoma via EMT

Liu, Yuanhua; Qian, Peipei; Zhu, Wei; Wu, Yuan; Liu, Delin; Zhang, Yan; Liang, Geyu; Shen, Bo

doi:10.7150/ijbs.34076

Cited by 47 publications

(53 citation statements)

References 20 publications

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“…But the mechanism for the increased ITPKA expression is complex and could be regulated by several molecular mechanisms including DNA methylation, microRNA, or aberrant transcription factor signaling. In the previous study from our lab, Liu et al determined that the transcription factor TFAP2A promotes tumor metastasis and EMT via activating cytokeratin KRT16 transcriptionally [8], in the current study we identified TFAP2A could also activate the expression of ITPKA, which is a new mechanism for the ITPKA hyper-expression in lung adenocarcinoma.…”

Section: Introductionsupporting

confidence: 61%

“…Because we already reported TFAP2A is also significantly hyper-expressed in LUAD [8]. We came to the conclusion that TFAP2A should be an important TF for ITPKA and contribute to the ITPKA hyper expression in LUAD.…”

Section: Tfap2a Is the Upstream Transcription Factor For Itpka And Itmentioning

confidence: 77%

“…Gene set enrichment analysis. GSEA was introduced for potential mechanism exploring [8][9][10], and the transcriptome data from 50 TCGA_LUAD tumor tissues were submitted for GSEA (based on ITPKA expression, top 25 (top 10%) versus bottom 25 (bottom 10%) from 511 TCGA_LUAD tumor samples). These results indicate that epithelial mesenchymal transition (EMT) might be the downstream mechanism for ITPKA's phenotype in LUAD ( Fig 3A & B).…”

Section: Itpka Is Involved With Epithelial Mesenchymal Transition (Emmentioning

confidence: 99%

“…To explore the clinical significance of ITPKA, a tissue microarray described before were introduced [8], the LUAD tissue microarray (TMA) contain 92 tumor samples with follow up survival data, after staining with ITPKA, in the multivariant cox regression survival analysis was performed, several clinical parameters including age, gender, pathology, T stage, N stage, TNM stage and ITPKA level were enrolled. As shown in Fig 6A, in normal lung tissues the ITPKA expression is very low, but LUAD tissues have higher ITPKA level, and the open access survival data from km-plot (http://kmplot.com) indicates higher ITPKA mRNA expression predicts worse prognosis ( Fig 6B) [12].…”

Section: Itpka Hyper Expression Predicts Poor Prognosis In Luadmentioning

confidence: 99%

“…Transfection was followed by instruction of Lipofectamine 3000 (Invitrogen, USA). The human ITPKA targeting small hairpin RNA (shRNA) was designed with the targeting sequence 5′-CCUUGUGUGCUCGACUGCA-3′ adopted from a published paper [14], and the DBN1 shRNA with 5′-GGAUUAACCGAGAGCAGUU-3′ targeting sequence was also introduced [15], the two shRNA were inserted into pGFP-C-shLenti vector for lentivirus packaging, and the expression plasmid with full length of ITPKA and the luciferase reporter plasmids (firefly luciferase) containing the core promotor region of ITPKA were both customized and ordered from RiboBio (Guangzhou, China); and a Renilla luciferase expression plasmid was used for background control, the method for determine the luciferase activity were described before [8].…”

Section: Cell Lines Cell Culture and Plasmidsmentioning

confidence: 99%

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TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma

Zhou¹,

Fan²,

Zhu³

et al. 2020

Int. J. Biol. Sci.

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The inositol polyphosphate kinase (IPK) family member ITPKA (inositol 1,4,5-trisphosphate 3-kinase) regulates the levels of many inositol polyphosphates which are important in cellular signaling. Several recent studies reported the aberrant expression of ITPKA in malignancy disease and usually made cancer more aggressive. However, the contribution of the inositol polyphosphate kinase ITPKA to lung cancer development remains unclear.Here we report that ITPKA is overexpressed in lung adenocarcinoma (LUAD) and positively correlated with advanced clinical parameters. ITPKA contributes to the malignant phenotypes in-vitro. Mechanistically, ITPKA executed its action through the inducting of epithelial-mesenchymal transition (EMT) and interacting with Drebrin 1 (which is related to cancer metastasis). Moreover, the hyper-expression of ITPKA in LUAD is transcriptionally activated by the transcription factor TFAP2A. In survival analysis by using tissue microarray (TMA), we indicate that ITPKA is hyper-expressed in LUAD tissues compared to adjacent normal tissues, and increased expression of ITPKA is associated with poor prognosis. Collectively, this study indicates that TFAP2A induced ITPKA hyperexpression promotes LUAD via interacting with Drebrin 1 and activating epithelial-mesenchymal transition (EMT). ITPKA might represent a potent candidate for the treatment and prognostic prediction of LUAD.

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Section: Introductionsupporting

confidence: 61%

Section: Tfap2a Is the Upstream Transcription Factor For Itpka And Itmentioning

confidence: 77%

Section: Itpka Is Involved With Epithelial Mesenchymal Transition (Emmentioning

confidence: 99%

Section: Itpka Hyper Expression Predicts Poor Prognosis In Luadmentioning

confidence: 99%

Section: Cell Lines Cell Culture and Plasmidsmentioning

confidence: 99%

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TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma

Zhou¹,

Fan²,

Zhu³

et al. 2020

Int. J. Biol. Sci.

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Integration of bioinformatics analysis and experimental validation identifies plasma exosomal miR‐103b/877‐5p/29c‐5p as diagnostic biomarkers for early lung adenocarcinoma

Feng

Wang

et al. 2022

Cancer Medicine

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The aim of this study was to identify miRNAs in plasma exosomes as noninvasive biomarkers for the early diagnosis of lung adenocarcinoma (LUAD). First, exosomal miRNA profiling of three patients with early LUAD and three patients with benign lung disease were screened by next‐generation sequencing (NGS) method. Sequencing results showed that 154 exosomal miRNAs were differentially expressed in the plasma of LUAD patients, among which 68 miRNAs were up‐regulated and 86 miRNAs were down‐regulated. GSE137140 is a GEO database containing serum miRNAs sequencing data from 1566 lung cancer patients and 1774 non‐cancer patients controls. When comparing the sequencing data, it was found that most miRNAs (37/68) up‐regulated in our LUAD group were also significantly up‐regulated in GSE137140, suggesting that circulating miRNAs in lung cancer patients may be enriched in plasma exosomes. In GSE137140, the AUC of the combination of hsa‐miR‐103b, hsa‐miR‐29c‐5p and hsa‐miR‐877‐5p was 0.873, showing great potential as new tumor markers. To our knowledge, these three exosomal miRNAs have not been reported in lung cancer research. Furthermore, bioinformatics tools were used to analyze the target genes of three candidate miRNAs, which were indeed closely related to the occurrence and development of lung cancer. Bioinformatics algorithms deduced a highly conserved sequence in the 3’‐UTR of SFRP4, FOXM1 and TMEM98 that could be bound with miR‐103b/877‐5p/29c‐5p. A luciferase assay indicated that miR‐103b/877‐5p/29c‐5p directly targeted the 3’‐UTR of SFRP4, FOXM1 and TMEM98, respectively. Finally, three candidate miRNAs were validated by qRT‐PCR in 17 early LUAD samples and 17 control plasma samples. Integration of bioinformatics analysis and experimental validation identifies, this study provides novel insights into miRNA‐related networks in LUAD. Hsa‐miR‐103b, hsa‐miR‐29c‐5p, and hsa‐miR‐877‐5p may be used as diagnostic biomarkers for early LUAD.

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High KRT17 expression in tumour budding indicates immunologically ‘hot’ tumour budding and predicts good survival in patients with colorectal cancer

Liang,

Jie,

Xie

et al. 2024

Clin & Trans Imm

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ObjectivesEmerging evidence has demonstrated that tumour budding (TB) is negatively associated with T‐lymphocyte infiltration in CRC. Despite extensive research, the molecular characteristics of immunologically ‘hot’ TB remain poorly understood.MethodsWe quantified the number of TB by haematoxylin–eosin (H&E) sections and the densities of CD3+ and CD8+ T‐lymphocytes by immunohistochemistry in a CRC cohort of 351 cases who underwent curative resection. We analysed the differential expression and T‐lymphocyte infiltration score of 37 human epithelial keratins in CRC using RNA sequencing from the TCGA dataset. In 278 TB‐positive cases, KRT17 expression was evaluated in tumour centre (TC) and TB with a staining score. Patient demographic, clinicopathological features and survival rates were analysed.ResultsIn a CRC cohort of 351 cases, low‐grade TB was associated with high CD3+ and CD8+ T‐cell densities in the invasive margin (IM) but not in the TC. Of 37 human epithelial keratins, only KRT17 expression in TB had an apparent association with TB‐grade and T‐lymphocyte infiltration. In 278 TB‐positive cases, high KRT17 expression in TB (KRT17TB) was negatively associated with low‐grade TB and positively associated with high CD3+ and CD8+ T‐cell densities in IM. High KRT17TB predicted early tumour grade, absence of lymph node metastasis and absence of tumour deposits. Additionally, patients with high KRT17TB had good overall survival and disease‐free survival. Notably, low KRT17TB can specifically identify those patients with a poor prognosis among colorectal cancer patients with low TB and high T‐lymphocyte infiltration.ConclusionsKRT17 can be employed as a new indicator for distinguishing different immunological TBs.

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TFAP2A Induced KRT16 as an Oncogene in Lung Adenocarcinoma via EMT

Cited by 47 publications

References 20 publications

TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma

TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma

Integration of bioinformatics analysis and experimental validation identifies plasma exosomal miR‐103b/877‐5p/29c‐5p as diagnostic biomarkers for early lung adenocarcinoma

High KRT17 expression in tumour budding indicates immunologically ‘hot’ tumour budding and predicts good survival in patients with colorectal cancer

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