Lung adenocarcinoma (LUAD) is a prevalent type of thoracic cancer with a poor prognosis and high mortality rate. DNA methylation is a potential factor contributing to the development of LUAD, leading to chromosomal structural changes and potentially tumorigenesis. The baculoviral IAP repeat-encoded 5 (BIRC5) gene encodes the survivin protein, a multifunctional gene involved in tumor cell proliferation, migration, and invasion. Here, researchers identified eight hub genes with aberrant expression and significant alterations in DNA methylation in LUAD. BIRC5 is a marker significantly upregulated in tumor tissues. To investigate the role of BIRC5 in LUAD cell death, A549 cells and mouse xenografts were analyzed using flow cytometry, lactate dehydrogenase (LDH) release assays, and micro-PET imaging. The researchers found that BIRC5 expression was upregulated and associated with high mortality in LUAD patients. Mechanistically, knockdown of BIRC5 inhibited A549 cell proliferation and induced pyroptosis via the caspase3/GSDME signaling pathway. These findings suggest that BIRC5 may be a novel biomarker and therapeutic target for lung adenocarcinoma. Furthermore, the researchers discovered a new pathway by which inhibition of BIRC5 can induce pyroptosis in lung adenocarcinoma cells through the caspase3-GSDME pathway.
To further elucidate the in vivo function of BIRC5, the researchers generated a BIRC5 knockdown cell line (Figure 1a). The A549 cell line was then divided into three groups: control, si-BIRC5, and si-NC. The tumorigenicity of the cells from these different groups was assessed in xenografted mice. Static PET images were acquired 1 hour after 18F-FDG injection in the control, si-BIRC5, and si-NC groups. The researchers observed a significant reduction in tumor size in BIRC5 knockdown A549 xenografted mice compared to the NC group (Figure 1b). Furthermore, tumor volume and weight were significantly reduced in BIRC5 knockdown A549 xenografted mice compared to the NC group (Figures 1c-e). Cell viability and migration of A549 cells were assessed using CCK8 and Transwell assays. The results showed that BIRC5 inhibition significantly suppressed cell survival and migration (Figures 1f, g). These data demonstrate that BIRC5 silencing exhibits anti-cancer effects both in vivo and in vitro.
Figure 1. The BIRC5 deletion inhibits LUAD progression. (Zhang Q, et al., 2023)