miRNA-381 regulates renal cancer stem cell properties and sunitinib resistance via targeting SOX4

Cancer stem cells (CSCs) are crucial in the pathogenesis of human cancers. Existing studies reported that microRNA (miRNA) modulates the stemness of CSCs. We discovered that renal cell CSCs have suppressed miR-381. Suppression of miR-381 promotes renal cell tumorigenesis and CSC-like properties. Furthermore, the forced expression of miR-381 prevents the renal cell tumorigenesis and CSC-like properties. Mechanistically, renal cell CSCs have been found to interact with SOX4 through miR-381 directly. miR-381 inhibits renal cell CSC-like properties and tumorigenesis via downregulating SOX4. Examination of the patient-derived xenografts (PDX) and patient cohorts reveals that miR-381 may be able to forecast the advantages of Sunitinib in RCC patients. Moreover, the introduction of SOX4 could reverse the sensitivity of miR-381 overexpression RCC cells to Sunitinib-induced cell apoptosis. These results indicated that miR-381 is critical in renal cell CSC-like properties and tumorigenesis, making it the ideal therapeutic target for RCC.