Abstract 6686: Bioinformatic evidence for the involvement of SP1, MYC, and HIF1A in the regulation of miRNAs and histone H2AZ1

Abstract We previously proposed the concept that the inhibitors for SP1, MYC, and HIF1A should induce strong anticancer activity by reducing the expression of stem cell-related proteins (Curr. Issues Mol. Biol. 2023, 45, 9262-9283). Then, it was shown that in LN229 and U87MG glioblastoma cells, either tetra-methyl-O-nordihydroguaiaretic acid (M4N) or tetra-acetyl-O-nordihydroguaiaretic acid (A4N) suppressed SP1 and only a few stem cell-related proteins and induced only a small amount of cell death while the combination treatment of M4N with A4N greatly suppressed the expression of SP1, MYC, and HIF1A, and all stem cell-related proteins examined, and greatly induced cell death. This data provided the biochemical evidences to support the aforementioned concept. In this study we did bioinformatic analysis to seek for further evidences to support this concept. The ontology analysis showed that the proteins associated with SP1, MYC, and HIF1A were specifically involved in the regulation of transcription and that various miRNAs which had been shown to induce either anti- or pro-cancer activity were associated with SP1, MYC, and HIF1A, which suggested that the inhibition of SP1, MYC, and HIF1A could modulate transcription of both coding and noncoding RNAs and affect cancers. It has been known that nucleosomes, containing histone variants H2AZ1, are important for gene transcription initiation and termination, chromosome segregation and DNA double-strand break repair. The network analysis showed that there were intricate connections between three transcription factors (SP1, MYC, and HIF1A) and H2AZ1. These data overall showed that SP1, MYC, and HIF1A in combination played important roles in transcription regulations via multiple ways (modulations of both coding and non-coding RNAs, miRNAs, and H2AZ1) and that the inhibitions of these transcription factors should have strong negative impacts on cancers which required enhanced production of energy and materials for their rapid proliferation. Thus, these bioinformatic data overall supported our concept as well. Citation Format: Kotohiko Kimura, Monika Rajput, John Ho Chun, Ru Chih C. Huang. Bioinformatic evidence for the involvement of SP1, MYC, and HIF1A in the regulation of miRNAs and histone H2AZ1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6686.