miR-143-3p: A Critical Regulator of KRAS and HRAS with Potential for Targeted Therapies in Breast Cancer

Breast cancer is a heterogeneous disease with distinct subtypes, including the highly aggressive triple-negative breast cancer (TNBC), which lacks estrogen, progesterone, and HER2 receptors. The rapid recurrence, high metastatic potential, and poor clinical outcomes of breast cancer are driven by dysregulated signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, and JAK/STAT, which contribute to breast cancer progression, therapy resistance, and metastasis. Among these, the Ras family of proteins, particularly KRAS and HRAS, is pivotal in promoting tumor survival, epithelial-to-mesenchymal transition (EMT), and chemotherapy resistance. Recent research highlights the regulatory role of microRNAs (miRNAs) in these pathways, with miR-143-3p emerging as a critical modulator of the RAS signaling cascade. miR-143-3p acts as a tumor suppressor by targeting key components of the RAS pathway, including KRAS, thereby influencing downstream effectors. This regulation impacts cellular processes such as proliferation, apoptosis, and EMT, crucial in breast cancer progression and therapeutic resistance. This review focuses on the role of miR-143-3p in breast cancer, particularly its regulation of the RAS pathway. It discusses its potential as a therapeutic target for improving outcomes in aggressive breast cancer subtypes. HIGHLIGHTS This article reviewed how miR-143-3p targets KRAS and HRAS and influences breast cancer cell proliferation, apoptosis, and migration and development of miR-143-3p carrier agent. miR-143-3p targets KRAS and HRAS both directly and indirectly. Several miR-143-3p carriers, organic and inorganic, have been developed to increase their stability, bioavailability, and efficiency in targeting cancer cells. GRAPHICAL ABSTRACT