Evidence to Support the Collaboration of SP1, MYC, and HIF1A and Their Association with microRNAs

Jong Ho Chun; Kotohiko Kimura; Monika Rajput; Ming-Hua Hsu; Yu-Chuan Liang; Akanksha Ramadas Shanbhag; Pei-Ju Chiang; Tiffany L B Jackson; Ru Chih C Huang

doi:10.3390/cimb46110741

Evidence to Support the Collaboration of SP1, MYC, and HIF1A and Their Association with microRNAs

Curr Issues Mol Biol. 2024 Nov 5;46(11):12481-12496. doi: 10.3390/cimb46110741.

Authors

Jong Ho Chun¹, Kotohiko Kimura¹, Monika Rajput^{1

2}, Ming-Hua Hsu³, Yu-Chuan Liang⁴, Akanksha Ramadas Shanbhag^{1

5}, Pei-Ju Chiang⁶, Tiffany L B Jackson¹, Ru Chih C Huang^{1

7}

Affiliations

¹ Department of Biology, Johns Hopkins University, 3400 N. Charles St-Levi Hall 250, Baltimore, MD 21218, USA.
² Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
³ Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan.
⁴ Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan.
⁵ Advanced Academic Programs, Johns Hopkins University, Baltimore, MD 21218, USA.
⁶ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
⁷ Academia Sinica, Taipei 115, Taiwan.

Abstract

This study provides evidence to support the concept proposed by Kimura et al. in 2023 that the inhibitors of SP1, MYC, and HIF1A should induce strong anticancer activity by reducing the expression of stem cell-related proteins. 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; in contrast, the combination treatment of M₄N with A₄N greatly suppressed the expression of SP1, MYC, and HIF1A, as well as all of the stem cell-related proteins examined, and greatly induced cell death. The bioinformatic analysis showed that the proteins associated with SP1, MYC, and HIF1A were specifically involved in the regulation of transcription and that various microRNAs (miRNAs) that had been shown to induce either anti- or procancer activity were associated with SP1, MYC, and HIF1A, which suggested that the inhibition of SP1, MYC, and HIF1A could modulate the transcription of both coding and noncoding RNAs and affect cancers. These data overall supported our concept.

Keywords: HIF1A; M4N; MYC; SP1; anticancer; stem cell.

Grants and funding

This study was supported by grants from the National Institutes of Health (R01DE12165), 806 Biocure medical, LLC, and the Dorothy Yen Trust (P 690-C25-2407) to RCH. The funders had no role in the conceptualization, design of the study, interpretation of the data, decision to publish, or preparation of the manuscript.