Human SERPING1 Stable Cell Line - A549

The long-term prognosis for patients with lung cancer (LC) remains grim, with lung adenocarcinoma (LUAD) emerging as the predominant histological subtype. Mendelian randomization (MR) studies have revealed that elevated levels of circulating Serpin Family G Member 1 (SERPING1) can significantly reduce the risk of lung cancer. Analyses employing multi-omics strategies indicate that, compared to healthy individuals, LUAD patients exhibit a downward trend in SERPING1 expression levels within both tissue and serum samples; conversely, within the LUAD patient cohort, individuals demonstrating higher levels of SERPING1 expression tend to experience better clinical outcomes. Furthermore, SERPING1 expression levels demonstrate a strong correlation with the efficacy of immunotherapy. Through a combination of in vitro and in vivo experiments, researchers have elucidated that SERPING1 inhibits the proliferation, migration, invasion, and wound-healing capabilities of LUAD cells via the Tuberous Sclerosis Complex 2 (TSC2)/mammalian Target of Rapamycin (mTOR) signaling pathway. Mechanistically, the WNT Inhibitor Specific Protein 5 (SP5) promotes the transcription of SERPING1 by binding to the promoter region of the SERPING1 gene. Notably, aside from its established associations with systolic blood pressure, glycated hemoglobin (HbA1c), and Type 1 diabetes, there is currently no definitive evidence to suggest a significant link between high SERPING1 expression and an increased risk of developing other cardiometabolic diseases. In summary, SERPING1 has been identified as a novel tumor suppressor gene, and the SP5/SERPING1/TSC2 signaling axis holds great promise as a potential therapeutic target for the treatment of LUAD.

To validate the tumor-suppressive effect of SERPING1 in vivo, researchers established a nude mouse xenograft model (Figure 1A). First, the researchers successfully generated an A549 cell line stably overexpressing SERPING1 (Figure 1B). Subsequently, these SERPING1-overexpressing A549 cells were subcutaneously injected into nude mice to establish a tumor-bearing model. Tumor volume and body weight were measured every three days, and the mice were euthanized on day 31 post-inoculation (Figure 1C). Notably, no statistically significant differences in body weight were observed among the various groups of mice (Figure 1D). Strikingly, compared to the control group, both tumor volume (Figure 1E) and tumor weight (Figure 1F) were significantly reduced following the overexpression of SERPING1. Furthermore, immunohistochemistry (IHC) analysis confirmed that, following in vivo overexpression of SERPING1, SERPING1 exhibited high expression levels, whereas Ki67 and Type I collagen (COL1A1) exhibited low expression levels (Figure 1G). These results strongly substantiate the inhibitory role played by SERPING1 in the progression of LUAD in vivo.

Figure 1. SERPING1 restrained LUAD progression in vivo. (Shen Y, et al., 2025)