ΔNp63 to TAp63 expression ratio as a potential molecular marker for cervical cancer prognosis

Park, Sunyoung; Lee, Suji; Kim, Jungho; Kim, Geehyuk; Park, Kwang Hwa; Kim, Tae Ue; Chung, Dawn; Lee, Hyeyoung

doi:10.1371/journal.pone.0214867

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…To investigate whether miR-944 interacts with p63 , which is the miR-944 host gene, the expression levels of two major isoforms of TAp63 and ΔNp63 mRNAs were compared with miR-944 expression levels. The mRNA expression levels of TAp63 and ΔNp63 were divided into negative and positive groups according to a cut-off value identified by receiver operator characteristic (ROC) curve analysis in normal and cervical cancer tissues [ 22 ]. Hence, the expression levels of miR-944 were compared in the TAp63 - and ΔNp63 -positive and negative groups.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, it was hypothesized that miR-944 may be functionally connected to its host gene, TP 63, especially ΔNp63 , in cervical cancer. Previous studies showed that ΔNp63 mRNA expression levels were significantly higher in the ME-180, SiHa, CaSki, and C33A cell lines than TAp63 mRNA expression levels and that miR-944 expression levels in ME-180, CaSki, and C4I were higher than those in other cervical cancer cell lines such as HeLa, SW756, and C33A [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…ΔNp63 in breast and esophageal squamous carcinoma was previously reported to act as an activator of cell migration and invasion [ 30 , 31 ]. ΔNp63 was also highly expressed in several cancer tissues such as esophageal squamous cell carcinoma and cervical cancer with poor prognosis [ 22 , 32 ]. Similarly, our results also demonstrated that ΔNp63 induces apoptosis and activates migration and invasion in cervical cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Synergetic Effects of Intronic Mature miR-944 and ΔNp63 Isoforms on Tumorigenesis in a Cervical Cancer Cell Line

Kim

Park

Chang

et al. 2020

IJMS

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miR-944 is located in an intron of the tumor protein p63 gene (TP63). miR-944 expression levels in cervical cancer tissues are significantly higher than in normal tissues and are associated with tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and survival. However, associations of miR-944 with its host gene, TP63, which encodes TAp63 and ΔNp63, in cervical cancer have not been fully investigated. A positive correlation between miR-944 and ΔNp63 mRNA expression was identified in cervical cancer tissues. Furthermore, when the expression of miR-944 and ΔNp63 was simultaneously inhibited, cell proliferation-, differentiation- epithelial–mesenchymal transition (EMT)-, transcription-, and virus-associated gene clusters were shown to be significantly more active according to functional annotation analysis. Cell viability and migration were more reduced upon simultaneous inhibition with anti-miR-944 or ΔNp63 siRNA than with inhibition with anti-miR-944 or ΔNp63 siRNA alone, or scramble. In addition, Western blot analysis showed that the simultaneous inhibition of miR-944 and ΔNp63 reduced EMT by increasing the expression of epithelial markers such as claudin and by decreasing mesenchymal markers such as N-cadherin and vimentin. Slug, an EMT transcription factor, was also decreased by the simultaneous inhibition of miR-944 and ΔNp63. Thus, associations between miR-944 and ΔNp63 in cervical cancer could help to elucidate the function of this intronic microRNA and its role in carcinogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Synergetic Effects of Intronic Mature miR-944 and ΔNp63 Isoforms on Tumorigenesis in a Cervical Cancer Cell Line

Kim

Park

Chang

et al. 2020

IJMS

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“…p63 is a transcription factor and a member of the same family as p53. Two isoforms of this protein have been identified, one with a normal transactivation domain and another, ΔNp63 with a truncated transactivation domain, and thus has an opposite function to that of p53, showing carcinogenic activity ( 115 ). miR-203 and ΔNp63 showed higher levels of expression in cervical tissues obtained from UCC compared with premalignant cervical lesions.…”

Section: The Role Of Ncrnas In Hpv-induced Uccmentioning

confidence: 99%

The role of HPV‑induced epigenetic changes in cervical carcinogenesis (Review)

et al. 2021

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Cervical cancer is associated with infection by certain types of human papillomaviruses (HPVs), and this affects women worldwide. Despite the improvements in prevention and cure of HPV-induced cervical cancer, it remains the second most common type of cancer in women in the least developed regions of the world. Epigenetic modifications are stable long-term changes that occur in the DNA, and are part of a natural evolutionary process of necessary adaptations to the environment. They do not result in changes in the DNA sequence, but do affect gene expression and genomic stability. Epigenetic changes are important in several biological processes. The effects of the environment on gene expression can contribute to the development of numerous diseases. Epigenetic modifications may serve a critical role in cancer cells, by silencing tumor suppressor genes, activating oncogenes, and exacerbating defects in DNA repair mechanisms. Although cervical cancer is directly related to a persistent high-risk HPV infection, several epigenetic changes have been identified in both the viral DNA and the genome of the infected cells: DNA methylation, histone modification and gene silencing by non-coding RNAs, which initiate and sustain epigenetic changes. In the present review, recent advances in the role of epigenetic changes in cervical cancer are summarized.

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“…Gene targets of TAp63 and ΔNp63 are also partially different [18,24]. The distinction of ΔNp63 and TAp63 in clinical samples may be important because p63 expression patterns are associated with clinicopathological features of tumours and long-term prognosis [39,40]. ΔNp63 has a dominant-negative effect on p53 and p63 function [18] because it is able to functionally inactivate p53 [27].…”

Section: Introductionmentioning

confidence: 99%

Pan-p63 but not ΔNp63 (p40) expression in undifferentiated carcinoma of the pancreas

Liszka

2020

pjp

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Undifferentiated carcinoma of the pancreas (UC) is a carcinoma without a definitive direction of differentiation. Tumour protein p63 is a regulator of squamous phenotype, which may also be engaged in tumour development. N-terminal isoforms of p63 are TAp63 and ΔNp63. Pan-p63 antibodies are able to detect both isoforms, whereas p40 antibodies recognise the ΔNp63 isoform only. The aim of the study was to describe pan-p63/p40 immunohistochemical expression patterns in pancreatic neoplasms: UC, ductal adenocarcinomas, neuroendocrine tumours, neuroendocrine carcinomas, serous cystic neoplasms, and solid pseudopapillary neoplasms. DAK-p63 and BC28 antibodies were used for pan-p63 and p40 detection, respectively. Moderate-to-strong pan-p63 was found in anaplastic (pleomorphic giant cell) UC (n = 4), sarcomatoid UC (n = 2), UC with osteoclast-like giant cells (n = 3), and ductal carcinomas with partial squamous differentiation. Weak and focal pan-p63 expression was found in monomorphic UC (n = 3) and in the majority of neuroendocrine carcinomas (6/7 cases). Pan-p63 expression was infrequent in ductal carcinomas without squamous differentiation and in neuroendocrine tumours. Serous cystic and solid pseudopapillary neoplasms were pan-p63-negative. Ductal carcinomas with partial squamous differentiation were the only tumours with evident p40 expression. Pan-p63(+)/p40(-) immunohistochemical status may be supportive for UC diagnosis. The pan-p63 expression was not equivalent to squamous differentiation in pancreatic neoplasia.

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ΔNp63 to TAp63 expression ratio as a potential molecular marker for cervical cancer prognosis

Cited by 11 publications

References 29 publications

Synergetic Effects of Intronic Mature miR-944 and ΔNp63 Isoforms on Tumorigenesis in a Cervical Cancer Cell Line

Synergetic Effects of Intronic Mature miR-944 and ΔNp63 Isoforms on Tumorigenesis in a Cervical Cancer Cell Line

The role of HPV‑induced epigenetic changes in cervical carcinogenesis (Review)

Pan-p63 but not ΔNp63 (p40) expression in undifferentiated carcinoma of the pancreas

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