FBLN2 inhibits gastric cancer proliferation and metastasis via the TGFβ/TGIF2 pathway

Abstract

Gastric cancer (GC) ranks among the most common gastrointestinal tumours and is a significant contributor to cancer mortality globally. The proliferation, metastasis, occurrence and development of GC have obvious malignant tendencies. This study is based on our previous studies. Previously, we reported that Fibulin-2 (FBLN2) can inhibit the distant metastasis of GC by promoting lost-nest apoptosis. Despite its clinical importance, the biological function of FBLN2 in GC remains inadequately understood. This study investigated the underlying molecular mechanisms of FBLN2 in the pathogenesis and progression of GC, as well as its impact on the biological behaviour of GC cells. In vivo and in vitro experiments, we demonstrated that FBLN2 overexpression resulted in a reduction in GC cell proliferation and metastasis, whereas its knockdown led to enhancement of GC proliferation and metastasis. Moreover, we used RNA-seq technology to conduct KEGG enrichment analysis of differential genes in wild-type GC cells and FBLN2 knockout GC cells and successfully confirmed that FBLN2 plays a corresponding biological role through the TGFβ/TGIF2 axis. In addition, in terms of the clinical data, we revealed a correlation between FBLN2 and TGIF2 and patient prognosis. In summary, our study revealed that FBLN2 suppressed GC proliferation, migration and invasion by downregulating the TGFβ/TGIF2 axis, suggesting that FBLN2 is a promising target for GC treatment.