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PAX9 在癌症发生发展中的作用。

PAX9 in Cancer Development.

机构信息

Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC 27707, USA.

Department of Thoracic Surgery, National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli Road, Beijing 100021, China.

出版信息

Int J Mol Sci. 2022 May 17;23(10):5589. doi: 10.3390/ijms23105589.

DOI:10.3390/ijms23105589
PMID:35628401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9147292/
Abstract

Paired box 9 (PAX9) is a transcription factor of the PAX family functioning as both a transcriptional activator and repressor. Its functional roles in the embryonic development of various tissues and organs have been well studied. However, its roles and molecular mechanisms in cancer development are largely unknown. Here, we review the current understanding of PAX9 expression, upstream regulation of PAX9, and PAX9 downstream events in cancer development. Promoter hypermethylation, promoter SNP, microRNA, and inhibition of upstream pathways (e.g., NOTCH) result in PAX9 silencing or downregulation, whereas gene amplification and an epigenetic axis upregulate PAX9 expression. PAX9 may contribute to carcinogenesis through dysregulation of its transcriptional targets and related molecular pathways. In summary, extensive studies on PAX9 in its cellular and tissue contexts are warranted in various cancers, in particular, HNSCC, ESCC, lung cancer, and cervical SCC.

摘要

配对盒 9（PAX9）是 PAX 家族的转录因子，既能作为转录激活因子，也能作为转录抑制因子。其在胚胎发育过程中对各种组织和器官的功能作用已得到充分研究。然而，其在癌症发展中的作用和分子机制在很大程度上尚不清楚。本文综述了 PAX9 的表达、上游调控以及在癌症发展中的下游事件的最新研究进展。启动子超甲基化、启动子 SNP、微小 RNA 以及上游通路（如 NOTCH）的抑制导致 PAX9 沉默或下调，而基因扩增和表观遗传轴则上调 PAX9 的表达。PAX9 可能通过其转录靶标和相关分子通路的失调而促进肿瘤发生。总之，在各种癌症中，特别是在头颈部鳞状细胞癌、食管鳞状细胞癌、肺癌和宫颈癌中，需要在细胞和组织背景下对 PAX9 进行广泛研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/7fde67080a80/ijms-23-05589-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/df38309cf242/ijms-23-05589-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/a586d0485826/ijms-23-05589-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/7b303ca56b26/ijms-23-05589-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/e4988dde2cd2/ijms-23-05589-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/7cffc73a255c/ijms-23-05589-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/7fde67080a80/ijms-23-05589-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/df38309cf242/ijms-23-05589-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/a586d0485826/ijms-23-05589-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/7b303ca56b26/ijms-23-05589-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/e4988dde2cd2/ijms-23-05589-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/7cffc73a255c/ijms-23-05589-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3f/9147292/7fde67080a80/ijms-23-05589-g006.jpg

相似文献

[1]
PAX9 in Cancer Development.

Int J Mol Sci. 2022-5-17

[2]
PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium.

J Pathol. 2017-12-1

[3]
The clinical significance and correlative signaling pathways of paired box gene 9 in development and carcinogenesis.

Biochim Biophys Acta Rev Cancer. 2021-8

[4]
PAX9 Determines Epigenetic State Transition and Cell Fate in Cancer.

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[5]
Transcriptional analysis of the human PAX9 promoter.

J Appl Oral Sci. 2010

[6]
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Gen Comp Endocrinol. 2007

[7]
PAX9 reactivation by inhibiting DNA methyltransferase triggers antitumor effect in oral squamous cell carcinoma.

Biochim Biophys Acta Mol Basis Dis. 2022-9-1

[8]
Alcohol drinking inhibits NOTCH-PAX9 signaling in esophageal squamous epithelial cells.

J Pathol. 2021-4

[9]
Prognostic value of PAX9 in patients with esophageal squamous cell carcinoma and its prediction value to radiation sensitivity.

Mol Med Rep. 2017-7

[10]
Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in human PAX9.

Hum Mol Genet. 2009-8-1

引用本文的文献

[1]
GWAS and 3D chromatin mapping identifies multicancer risk genes associated with hormone-dependent cancers.

PLoS Genet. 2024-11-25

[2]
Benchmarking of Approaches for Gene Copy-Number Variation Analysis and Its Utility for Genetic Aberration Detection in High-Grade Serous Ovarian Carcinomas.

Cancers (Basel). 2024-9-24

[3]
Onco-Ontogeny of Squamous Cell Cancer of the First Pharyngeal Arch Derivatives.

Int J Mol Sci. 2024-9-16

[4]
A novel PAX9 variant in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9variants.

Hua Xi Kou Qiang Yi Xue Za Zhi. 2024-10-1

[5]
Upregulation and functional roles of miR-450b in canine oral melanoma.

Noncoding RNA Res. 2024-2-1

[6]
Pan-cancer analysis reveals the characteristics and roles of tooth agenesis mutant genes.

Medicine (Baltimore). 2023-12-15

[7]
In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene.

Biochem Genet. 2024-8

[8]
Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants.

J Appl Oral Sci. 2023

[9]
PAX9 Is Involved in Periodontal Ligament Stem Cell-like Differentiation of Human-Induced Pluripotent Stem Cells by Regulating Extracellular Matrix.

Biomedicines. 2022-9-22

本文引用的文献

[1]
PAX9 functions as a tumor suppressor gene for cervical cancer via modulating cell proliferation and apoptosis.

Kaohsiung J Med Sci. 2022-4

[2]
Functional Screenings Identify Regulatory Variants Associated with Breast Cancer Susceptibility.

Curr Issues Mol Biol. 2021-10-26

[3]
Mutant clones in normal epithelium outcompete and eliminate emerging tumours.

Nature. 2021-10

[4]
Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype.

BMC Dev Biol. 2021-10-6

[5]
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.

Clin Epigenetics. 2021-8-28

[6]
A body map of somatic mutagenesis in morphologically normal human tissues.

Nature. 2021-9

[7]
PAX9 Determines Epigenetic State Transition and Cell Fate in Cancer.

Cancer Res. 2021-9-15

[8]
RETRACTED ARTICLE: Long non-coding RNA DIO3OS binds to microRNA-130b to restore radiosensitivity in esophageal squamous cell carcinoma by upregulating PAX9.

Cancer Gene Ther. 2022-6

[9]
The clinical significance and correlative signaling pathways of paired box gene 9 in development and carcinogenesis.

Biochim Biophys Acta Rev Cancer. 2021-8

[10]
Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers.

Cancer Res. 2021-5-15

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