miR-378f targets CAB39 to regulate autophagy in chemotherapy-induced peripheral neuropathy

Chemotherapy is the most common cancer therapy due to its ability to effectively destroy cancer cells. However, peripheral neuropathy is a notable side effect, which has no clearly established prevention or treatment methods. Although various therapeutic strategies using microRNAs (miRNAs) have been developed for a wide range of diseases, the role of miRNAs in neuroregeneration has yet to be elucidated. Our group previously identified five differentially expressed miRNAs in the plasma of patients with gastric cancer receiving XELOX (capecitabine and oxaliplatin) chemotherapy. Among these, miR-378f alone showed a significant correlation with peripheral neuropathy severity, providing the rationale for the present study. Bioinformatic analysis further predicted calcium-binding protein 39 (CAB39), a regulator of autophagy, as a shared target of these miRNAs. The downregulation of miR-378f increased CAB39 expression, activated AMPK and inhibited mTOR. Furthermore, changes in autophagy-related markers were observed, including increased Beclin-1 expression, elevated LC3-I to LC3-II conversion, and decreased p62 expression. The findings of the present study suggest that autophagy regulation by miR-378f may be a novel diagnostic and therapeutic target for peripheral neuropathy.