A Study of Molecular Mechanism of CSMD1 as a Tumor Suppressor in Lung Cancer

Abstract

Lung cancer accounts for a large portion of cancer patient mortality, but lung cancer treatment remained as a challenge for many people. Furthermore, most patients who use immune checkpoint inhibitors (ICIs) develop resistant tumor during or after treatment is discontinued. The CUB and Sushi multi- domain 1 (CSMD1) gene has been proposed as a tumor suppressor gene in many cancers. But the role of CSMD1 as a tumor suppressor in lung cancer is largely unknown. Thus, the objective of this study was to understand the function of CSMD1 as a tumor suppressor gene in lung cancer. CSMD1 over-expression in LLC1 shows inhibition of cell proliferation. And selected candidate genes from RNA- seq recover inhibition of cell proliferation by CSMD1 over-expression. It could possibly relate to the anti- tumor pathway of CSMD1. In BrdU/7-AAD assay, over-expression of CSMD1 decreased S phase. It suggests that the decrease in cell proliferation by CSMD1 expression possibly due to cell cycle arrest. In the tumor allograft model, induction of CSMD1 expression through doxycycline treatment tend to have less cancer metastasis than the control group. The control group showed significantly lower protein expression of pan-cytokeratin and lower ki-67 score than the doxycycline treatment group. It indicates that there were fewer lung cancer cells, which suggest that there was less lung metastasis. Considering that the gene expression level of CSMD1 was significantly higher in the doxycycline treatment group, this suggests that CSMD1 inhibits lung cancer metastasis. Taken together, our results suggest that CSMD1 could function as a biomarker for diagnosing lung cancer or be applied as a immunotherapy target.