miR-138-5p: From Multidimensional Tumor-Suppressive Regulatory Networks to Nanocarrier-Based Delivery for Solid Tumor...

MicroRNA-138-5p (miR-138-5p) has been reported to exert tumor-suppressive effects in several solid tumors, and its downregulation has been associated with malignant progression, therapeutic resistance, and poor prognosis.

This review summarizes research trends and current evidence on the molecular functions, regulatory networks, and therapeutic potential of miR-138-5p in solid tumors, with particular emphasis on competing endogenous RNA (ceRNA) regulation and nanocarrier-based delivery strategies.

Bibliometric analysis and CiteSpace visualization were conducted using English-language original articles and reviews retrieved from the Web of Science Core Collection from January 2014 to October 2025. Relevant literature was reviewed to examine miR-138-5p expression, biological functions, target genes, signaling pathways, ceRNA networks, and therapeutic strategies. Studies focused exclusively on hematological malignancies were excluded.

Bibliometric mapping identified research clusters spanning multiple solid tumor types, cell-cycle regulation, and proliferation, while metabolic reprogramming and therapeutic resistance emerged as relevant research themes. Mechanistic studies suggest that miR-138-5p regulates proliferation, apoptosis, migration, invasion, autophagy, immune-related signaling, and chemosensitivity through diverse targets and pathways. Long non-coding RNA- and circular RNA-mediated ceRNA networks have been proposed as an additional regulatory layer, although their physiological relevance requires further quantitative validation. Preclinical findings, including exosome-mediated delivery of miR-138-5p, suggest potential for replacement therapy; however, challenges involving delivery efficiency, tumor specificity, biosafety, pharmacokinetics, and manufacturing standardization remain.

miR-138-5p is a potential biomarker and therapeutic target in solid tumors. Further validation of its context-dependent mechanisms and optimization of targeted delivery strategies are needed to support clinical translation.