Regulation of PI3K Signaling by lncRNAs in Breast Cancer: A Mini-Review.

Abstract

Despite remarkable advancements, the treatment of breast cancer remains a serious challenge. In recent decades, extensive studies have been conducted to identify new therapeutic targets for the treatment of breast cancer. Among these therapeutic targets that have gained attention in recent years are lncRNAs. These molecules appear to affect proliferation, metastasis, and drug resistance in cancer cells by regulating multiple signaling pathways. Among the signaling pathways implicated in breast cancer, the PI3K/AKT/mTOR pathway is one of the most important. Given the frequent dysregulation of the PI3K/AKT/mTOR pathway in breast cancer, numerous recent studies have investigated its interplay with lncRNAs. Emerging evidence indicates that lncRNAs regulate the PI3K/AKT/mTOR pathway by modulating microRNA availability, influencing transcriptional programs, and serving as molecular platforms for chromatin-modifying complexes. This mini-review synthesizes recent evidence on lncRNAs targeting the PI3K/AKT/mTOR cascade in breast cancer, summarizing molecular mechanisms, functional consequences for proliferation, invasion, and therapy resistance, and available in vitro and in vivo evidence. Representative oncogenic lncRNAs (e.g., HOTAIR, DANCR, and LINC01133) and tumor-suppressive lncRNAs (e.g., MEG3 and ZFAS1) are discussed, together with their potential as therapeutic targets. Finally, the current challenges and future perspectives for integrating lncRNAtargeted approaches with PI3K pathway inhibition in breast cancer therapy are highlighted.