MicroRNA-125 (miR-125)

MicroRNA-125 (miR-125) is a highly conserved family of small non-coding RNAs, primarily comprising miR-125a and miR-125b, that function as master regulators of post-transcriptional gene expression [1, 9]. By binding to the 3' untranslated regions (UTRs) of target mRNAs, miR-125 induces translational repression or mRNA degradation, thereby controlling essential biological processes such as cell differentiation, proliferation, and apoptosis [2, 15]. In human health, miR-125 plays a dual role as both a tumor suppressor and an oncogene (oncomiR), with its function being highly dependent on the specific cellular context and tissue type [10, 14]. Dysregulation of miR-125 is a hallmark of numerous diseases, including various solid tumors, hematological malignancies, cardiovascular disorders, and inflammatory conditions [3, 13, 23]. In oncology, it often modulates sensitivity to chemotherapeutic agents like cisplatin and paclitaxel by targeting pro-apoptotic or anti-apoptotic genes [18, 22]. Therapeutic development focuses on restoring miR-125 levels using synthetic mimics in cases of downregulation or using antagomirs to silence its activity when overexpressed [17, 25]. Despite its therapeutic potential, challenges such as off-target effects and the need for efficient tissue-specific delivery systems remain significant hurdles for clinical translation [6, 29].

Other names

miR-125 familyhsa-miR-125ahsa-miR-125bMIR125AMIR125B1MIR125B2miR-125a-5pmiR-125b-5p

Therapeutic agents targeting microRNA-125 operate by either replenishing deficient levels of the microRNA using synthetic double-stranded RNA mimics to restore its tumor-suppressive functions, or by employing single-stranded antisense oligonucleotides (antagomirs or antimiRs) to bind and sequester the microRNA, thereby preventing it from silencing its target mRNAs when it acts as an oncogene [15, 17, 25].