Non-Coding RNAs in breast cancer bone metastasis: Regulators and novel therapeutic targets

Bone metastasis is one of the most common complications in patients with advanced breast cancer, severely impairing quality of life and significantly increasing the risk of mortality. This process is driven by complex interactions between tumor cells and the bone microenvironment, where non-coding RNAs (ncRNAs) act as key regulatory molecules playing a central role. This article systematically reviews the expression changes, molecular mechanisms, and biological functions of microRNAs, long non-coding RNAs, and circular RNAs in breast cancer bone metastasis. Studies have demonstrated that these ncRNAs precisely regulate tumor cell colonization and proliferation in bone, osteoclast-mediated bone resorption, and osteoblast-mediated bone formation through multiple mechanisms - including competitive endogenous RNA networks, signaling pathway modulation, exosome-mediated intercellular communication, and even the encoding of functional short peptides - thereby disrupting bone homeostasis. Simultaneously, ncRNAs can also regulate the occurrence of bone metastasis by modulating the immune microenvironment in breast cancer. Furthermore, ncRNAs exhibit significant clinical translational potential in the early diagnosis, prognostic evaluation, and targeted therapy of breast cancer bone metastasis. By synthesizing the ncRNA regulatory networks, this review aims to provide a theoretical basis and research directions for further exploring the molecular mechanisms of breast cancer bone metastasis and developing novel therapeutic strategies.