BACKGROUND: Acquired resistance to temozolomide is a major challenge for the effective treatment of glioblastoma (GBM). TRIML2, a member of the TRIM family, plays an important role in cancer genesis, progression, and treatment resistance. However, its mechanism of action in GBM resistance to temozolomide remains unclear. METHODS: RNA bulk sequencing data from temozolomide-resistant U87 cells and wild-type U87 cells were downloaded from the NCBI public database (GEO: GSE193957) and analyzed. A temozolomide-resistant cell line (U87-TR) was induced with temozolomide, and the expression of TRIML2 in temozolomide-resistant and wild-type cell lines (U87-WT) was verified by cell activity assays, wound-healing assays, and western blotting. The alteration of resistance to temozolomide was assessed following the overexpression of TRIML2 in the resistant cell line by lentiviral transfection. The differences in TRIML2 expression between primary GBM and recurrent GBM after temozolomide chemotherapy were verified by immunofluorescence, immunohistochemistry, and western blotting. RESULTS: The expression of TRIML2 was significantly lower in U87-TR cells than in U87-WT cells. After the TRIML2 overexpressed in U87-TR cells, their resistance to temozolomide was significantly decreased and became sensitive to temozolomide treatment. TRIML2 expression was significantly decreased in the temozolimide-resistant GBM tumors
in contrast, TRIML2 was relatively high expressed in the temozolimide-sensitive GBM tumors. CONCLUSIONS: TRIML2 inhibits temozolomide resistance in GBM and thus may serve as a novel therapeutic target for overcoming GBM resistance to temozolomide.