Role of LASP-1, a novel SOX9 transcriptional target, in the progression of lung cancer.

Lung cancer accounts for most cancer-related deaths worldwide. However, the underlying mechanism by which it mediates the progression of lung cancer remains unclear. Expression of LASP-1 (LIM and SH3 protein 1) was evaluated in lung cancer tissues and tumor-adjacent normal tissues using immunohistochemistry and western blotting. Functional studies have shown that siRNA-mediated silencing of LASP-1 in human lung cancer cells and reduced cell proliferation, migration, and invasion. Flow cytometry and immunofluorescence staining also revealed that rate of cell apoptosis was increased after knockdown of expression of LASP-1, thereby suggesting that LASP-1 may function as an oncogene during lung cancer progression. SOX9 is an important transcription factor, which is involved in the development of several types of human cancer. Further analysis has showed the presence of a consensus-binding site of SOX9 in the promoter region of LASP-1. Mechanistic investigations showed that LASP-1 was transcriptionally activated by SOX9. Through luciferase reporter and ChIP assays, we demonstrated that LASP-1 was a direct target gene of sex determining region Y-box 9 (SOX9). Knockdown of SOX9 expression by RNA interference reduces cell proliferation and induces apoptosis of lung cancer cells, which was consistent with the results obtained from silencing the expression of LASP-1 in NCI‑H1650 cells. Together, these findings indicated that LASP-1, as a downstream target of SOX9, may act as a novel biomarker for lung cancer and plays an important role in cell proliferation, migration, and invasion.