TRIM36 enhances lung adenocarcinoma radiosensitivity and inhibits tumorigenesis through promoting RAD51 ubiquitination and antagonizing hsa-miR-376a-5p.

The tripartite motif (TRIM) family proteins exhibit oncogenic or anti-oncogenic roles in various cancers. As a TRIM family member, TRIM36 is expressed in lung adenocarcinoma (LUAD), but its roles remain unexplored. Here, we set to investigate the clinical relevance and the biological actions of TRIM36 in LUAD. mRNA levels of TRIM36 and the Kaplan-Meier survival analysis for patients with LUAD were analyzed from The Cancer Genome Atlas (TCGA) database. Real-time PCR and western blotting were utilized to measure TRIM36 levels both in vivo and in vitro. We demonstrated that TRIM36 levels were significantly decreased in LUAD patients. The low expression of TRIM36 was correlated with a poor prognosis. Overexpression and knock-down studies illustrated that TRIM36 inhibits cell proliferation and promotes apoptosis in LUAD cell lines. LUAD cells were irradiated with 60Co. In addition, TRIM36 enhanced radiosensitivity in LUAD cell lines. Moreover, we found that TRIM36 expression was negatively associated with RAD51. Co-overexpressing RAD51 blocked TRIM36's effects on proliferation and apoptosis. TRIM36 formed a complex with RAD51, promoting its ubiquitination. Inhibiting hsa-miR-376a-5p enhanced apoptosis and the effects were mediated by TRIM36 in response to radiation. In conclusion, our results indicated that TRIM36 is anti-oncogenic in LUAD by promoting RAD1 ubiquitination. Hsa-miR-376a-5p acts upstream of TRIM36. TRIM36 and RAD1 may serve as prognostic indicators for LUAD. The interactions between TRIM36, RAD1 and hsa-miR-376a-5p can be future therapeutic targets to increase radiation sensitivity in LUAD patients. • Downregulation of TRIM36 contributed to the poor prognosis of LUAD. • TRIM36 inhibited proliferation and promoted apoptosis in LUAD cells. • TRIM36 was negatively related to DNA repair in LUAD cells. • TRIM36 increased radiation-sensitivity by promoting RAD51 ubiquitination. • miR-376a-5p acted as an upstream regulator of TRIM36. [ABSTRACT FROM AUTHOR]