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

**Authors:** Xin Hu, Rui Chen, Famin Ke, Dandan Wang, Xiaowei Gao, Can Song, Aimin Fu, Zuojin Ao, Hanyu Yang, Xiaoyan Liu, Xiurong Guo, Qiuyu Liu

PMC · DOI: 10.3390/cimb48010098 · 2026-01-18

## TL;DR

This paper reviews how hypoxia and non-coding RNAs interact in breast cancer to influence tumor growth and treatment resistance.

## Contribution

The paper systematically outlines the molecular interactions between hypoxia signaling and non-coding RNAs in breast cancer progression.

## Key findings

- Hypoxia-inducible factors like HIF-1α drive adaptive tumor responses such as angiogenesis and metabolic changes.
- Non-coding RNAs play regulatory roles in breast cancer development and progression under hypoxic conditions.
- The crosstalk between HIFs and ncRNAs remains poorly understood but has potential clinical implications.

## Abstract

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.

## Linked entities

- **Genes:** HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091]
- **Proteins:** HIF1A (hypoxia inducible factor 1 subunit alpha)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}
- **Diseases:** Breast Cancer (MESH:D001943), Hypoxia (MESH:D000860), metastasis (MESH:D009362), tumor (MESH:D009369), hypoxic (MESH:D002534)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12840453/full.md

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Source: https://tomesphere.com/paper/PMC12840453