Paper Title
Foxp3 Acts as a Transcription Repressor for Mir-325-3p and Encourages Tumour-Associated Treg Cells Differentiation and Proliferation in Tumour Microenvironment

Abstract
Cancer stages increase CD4+ FoxP3+ T Regulatory cells. Treg cells promote cancer. Cancer Micro RNAs increasingly affect Treg cell development and function. In cancers like breast cancer, micro RNA hsa-325-3p (mir-325-3p) regulates Treg homeostasis. We examined tumor-induced Treg cell miR-325-3p transcriptional regulation in vitro and in vivo. TATA box 940–720 bp regulates this. ShRNA-mediated downregulation, ChIP of RNA Pol II and FoxP3, site-directed mutagenesis, and promoter time chase analysis confirmed that Forkhead Box P3 (FoxP3, also known as Scurfin) interacts with these binding sites and down-regulates miR-325-3p expression. Treg cells increase FoxP3 and decrease miR-325-3p. Inhibiting FoxP3-mediated miR-325-3p inactivation improved tumor-induced T-regulatory cell development, survival, and migration. Our findings show the mechanistic basis of hsa-miR-325-3p gene regulation in Treg cells and support a direct interaction between miR-325-3p and FoxP3, two critical regulators of T regulatory cells exploited by the tumour microenvironment to promote tumour cell growth and metastasis.