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