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. Strong correlation between estrogen binding to its receptors α or β, was found, followed by expression of PDLIM3 gene, and activation of RUNX-2 expression through regulation of specifically miR-9 and miR-10. Also a novel miRNA, was determined, that is integrated in the activation of RUNX-2 through transcription of PDLIM3 gene.