Sufu mutation promotes malignant progression of lung adenocarcinoma by regulating Gli1

Abstract

Objective To explore the effect of Sufu on lung adenocarcinoma by observing its mutation and the changes in Gli1 transcription after its mutation. Methods cBioPortal for Cancer Genomics was used to obtain the mutation status of Sufu in lung cancer. Four Sufu single base mutation vectors were constructed and transfected into lung adenocarcinoma cell lines A549 and H1975 to establish cells with Sufu overexpression and knockout. Wounding healing assay was employed to determine the effect of Sufu on cell migration, and RT-qPCR, immunofluorescence assay and dual luciferase reporter gene assay were utilized to explore the changes in Gli1 transcription after Sufu mutation. Results cBioPortal data showed that the mutation rate of Sufu in lung cancer was 11.76% in squamous cell carcinoma (2/17), 0.96% in adenocarcinoma (6/625), 1.01% in small cell lung cancer (4/396), and 0.69% in non-small cell lung cancer (77/11 227). The median survival of lung cancer patients was significantly decreased in those with Sufu mutation than those without (38.00 vs 54.34 months, HR=1.943, P < 0.05). A549 cells were sensitive to Sufu knockout, and it resulted in significant increase of the transcription level of Gli1 (P < 0.05). Overexpression of Sufu inhibited cell migration ability in both A549 and H1975 cells (P < 0.05). Sufu mutation had no significant influence on the location of Gli1 in the cells. The Sufu-T411M mutation up-regulated the the transcription level of Gli1 (P < 0.05). Conclusion Sufu has an inhibitory effect on lung adenocarcinoma metastasis, and can be regarded as a potential target for lung adenocarcinoma metastasis.

Keywords

• lung adenocarcinoma
• hedgehog signaling pathway
• sufu
• gli1