Estrogen-Driven Crosstalk Among RUNX-2, PDLIM3, and Novel microRNAs via ERG Signaling: A Network Meta-Analysis Using IPA

Estrogens govern the female reproductive cycle indefinitely. Estrogens, including estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4), regulate the female life cycle since early embryonic stages and play a crucial role in development, metabolism, and cell function. Throughout evolution, estrogen has regulated reproduction by affecting reproductive organ development and behavior. Estrogen impacts all vertebrates, including fish, and has a role in physiological and pathological states in both genders. RUNX-2 gene is a member of the RUNX family of transcription factors and encodes a nuclear protein with a Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. In 2022, a study was conducted to characterize novel genes that are regulated by estrogen binding to its receptors (α or β). The PDLIM3 gene, with a coefficient of variation (CV) of 0.083, received the most stable CV score among other genes. We found a strong correlation between estrogen binding to its receptors α or β, followed by expression of PDLIM3 gene, and activation of RUNX-2 expression through regulation of specifically miR-9 and miR-10. We also determined a novel miRNA that is integrated in the activation of RUNX-2 through transcription of PDLIM3 gene.