OBJECTIVETo investigate the role of USP33 as an independent prognostic marker in the regulation of SLIT2/ROBO1 signaling pathway to inhibit lung adenocarcinoma invasion and metastasis.

METHODSThe expression of USP33 in 20 lung adenocarcinoma specimens was detected by qPCR and immunohistochemistry. A549 and SPC-A-1 cells with small interfering RNA (siRNA)-mediated USP33 silencing were examined for changes in invasion and metastasis abilities using scratch assay and Matrigel assay. Western blotting was used to detect the expression of SLIT2 and ROBO1 in the cells after USP33 silencing and the expression of USP33 after interleukin-6 (IL-6) stimulation.

RESULTSqPCR and immunohistochemistry showed that USP33 was significantly decreased in lung adenocarcinoma tissues as compared with the adjacent tissues. USP33 silencing in A549 and SPC-A-1 cells significantly promoted the cell migration, invasion and metastasis and obviously down-regulated the expressions of SLIT2 and ROBO1. IL-6 stimulation of the cells obviously enhanced the expression of USP33.

CONCLUSIONSUSP33 silencing can promote the migration, invasion and metastasis of lung adenocarcinoma cells , and the mechanism may involve IL-6 and SLIT2/ROBO1 signaling pathways.