PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

Abstract

Metastasis is the most deadly aspect of cancer and results from acquired gene regulation abnormalities in tumor cells. Transcriptional regulation is an essential component of controlling of gene function and its failure could contribute to tumor progression and metastasis. During cancer progression, deregulation of oncogenic or tumor suppressive transcription factors, as well as master cell fate regulators, collectively influences multiple steps of the metastasis cascade, including local invasion and dissemination of the tumor to distant organs. Transcription factor PAX3/Pax3, which contributes to diverse cell lineages during embryonic development, plays a major role in tumorigenesis. Mutations in this gene can cause neurodevelopmental disease and the existing literature supports that there is a potential link between aberrant expression of PAX3 genes in adult tissues and a wide variety of cancers. PAX3 function is tissue-specific and could contribute to tumorigenesis either directly as oncogene or as a tumor suppressor by losing its function. In this review, we discuss comprehensively the differential role played by PAX3 in various tissues and how its aberrant expression is implicated in disease development. This review particularly highlights the oncogenic and tumor suppressor role played by PAX3 in different cancers and underlines the importance of precisely identifying tissue-specific role of PAX3 in order to determine its exact role in development of cancer.

BAX -248 G>A and BCL2 -938 C>A Variant Lowers the Survival in Patients with Nasopharyngeal Carcinoma and Could be Associated with Tissue-Specific Malignancies: A Multi-Method Approach

“…On the other side, BCL2 -938 C>A might change the binding affinity of PAX 9, PAX3, and CREB to the promoter. PAX gene family, including PAX3 and PAX9, plays the opposite role in BCL2 mediated apoptosis through the increase or decrease of its expression (Lee et al, 2008;Hirai et al, 2010;Tan et al, 2017;Arasu et al, 2018). Another TF, called cAMP response elementbinding protein (CREB) binds at the upstream promoter of BCL2 and up-regulates its expression (Wilson et al, 1996).…”

Non-coding RNA in rhabdomyosarcoma progression and metastasis

“…Pax3 and Pax7 transcription factors are known to be critical in activating the myogenic program whereby in their absence, muscle progenitor cells fail to enter myogenesis and complete differentiation into mature skeletal muscle fibers ( 94 ). However, their aberrant or sustained expression may prevent terminal differentiation of cells or contribute to tumorigenesis ( 48 , 55 , 95 , 96 ). Moreover, using gene and proteomic profiling, low levels of PAX7 transcript and protein were found to be necessary for miR-206-mediated differentiation and cell cycle exit of FN-RMS cells only, which may be due to the absence of miR-206 binding sites in the fusion oncoprotein of FP-RMS cells ( 55 ).…”

Chemical Synthesis of the PAX Protein Inhibitor EG1 and Its Ability to Slow the Growth of Human Colorectal Carcinoma Cells

“…Thus, increased proliferation of epithelial cells in the colon can alter the speed at which tumours form due to an increased likelihood that aberrant cell divisions will result in the acquisition of mutations, which then leads to a more progressive cancer (16,17). The oncogenic properties of PAX can be utilised to develop new cancer treatments by designing therapeutic targets to these proteins in the aim of slowing tumour growth (8,(18)(19)(20)(21).…”