TRIM55 suppresses malignant biological behavior of lung adenocarcinoma cells by increasing protein degradation of Snail1.

Up until now, cancer refractoriness and distal organ metastatic disease remain as major obstacles for oncologists to achieve satisfactory therapeutic effects for lung adenocarcinoma patients. Previous studies indicated that TRIM55, which participates in the natural development of muscle and cardiovascular system, plays a protective role in hepatocellular carcinoma (HCC) pathogenesis. Therefore, in this study, we aimed to unveil the detailed molecular mechanism of TRIM55 and identify the potential target for lung adenocarcinoma patients. Surgical samples and lung cancer cell lines were collected to detect the TRIM55 expression for patients with or without lymph node/distal organ metastasis. Cellular functional assays including transwell assay, wound healing assay, cellular survivability assay, etc. as well as ubiquitination assay were performed to evaluate the impact of TRIM55/Snail1 regulatory network via the UPP pathway on lung cancer tumor cell migration and chemo-resistance. Lung cancer tissues and tumor cell lines exhibited significantly lower levels of TRIM55 expression. Functional study further indicated that TRIM55 inhibited chemo-resistance, migration, and cancer stem-cell like phenotype of tumor cells. Further detailed molecular experiments indicated that TRIM55 promoted degradation of Snail1 via the UPP pathway, which played an interesting role in the regulation of cancer cell malignancy. This study provided novel theory that TRIM55 acted as a potential tumor suppressor by inhibition of tumor cell malignancy through enhancement of Snail1 degradation via the UPP pathway. Our research will inspire further exploration on TRIM55 to promote therapeutic effects for lung adenocarcinoma patients.