Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer

The hypoxic microenvironment within breast cancer tumors leads to the sustained activation of hypoxia-inducible factors (HIFs), notably HIF-1α, which, in turn, triggers adaptive responses such as angiogenesis and metabolic reprogramming. These processes contribute to tumor invasion, progression, metastasis, and therapy resistance. Although a substantial portion of the human genome is transcribed into non-coding RNAs (ncRNAs), which have been shown to play key regulatory roles in the development and progression of breast cancer, the interplay between HIFs and ncRNAs—and how such crosstalk influences breast cancer pathogenesis—remains poorly understood. This review aims to systematically outline the mechanisms of hypoxia-related signaling and ncRNA function in breast cancer, with a focus on their molecular interactions in disease progression and their potential clinical implications.