Purpose: This study aims to investigate the biological effect and molecular mechanism of Lamin B1(LMNB1) in lung cancer cells and its significance for the prognosis of lung adenocarcinoma(LUAD) patients.
Methods: In this study, Bioinformatics was performed to analyze the expression at mRNA level and prognosis effect of LMNB1 in LUAD from TCGA dataset. The immunohistochemistry(IHC) assay was conducted to analyzed the expression of LMNB1 at the protein level in LUAD tissues. The correlation between the expression of LMNB1 and the clinical factors in patients with LUAD was analyzed. Next, LMNB1 transfected into LUAD cell lines (A549 and PC-9) which was proved by Western blot. CCK8 assay, cloning formation assay, and xenograft assay were conducted to explore the effect and mechanism of LMNB1 on the proliferation of LUAD cell lines in vitro and in vivo.
Results: The results of the present study demonstrated that LMNB1 was highly expressed in LUAD tissues and related to tumor stage. High LMNB1 expression was related with more advanced clinicopathological factors such as low degree of differentiation (P=0.02), large tumor size (P< 0.01), lymph node metastasis (P< 0.01) and higher tumor stage (P< 0.01). After knocking down LMNB1, the cell growth rate (P< 0.01) and the number of colonies (P< 0.01) were significantly reduced, and the level of the proliferating marker Ki67 (P< 0.01) was significantly decreased. At the same time, in vivo experiments showed that the tumor volume and tumor of the mice were significantly reduced (P< 0.01). Moreover, we found that knockdown LMNB1 can inhibit the proliferation of lung cancer cells by inhibiting AKT phosphorylation by Western blot.
Conclusion: In summary, LMNB1 play an of vital roles in the growth of LUAD cells, highlighting its potential as a therapeutic target for the treatment of LUAD patients.
Keywords: lamin B1, lung adenocarcinoma, prognosis, malignant behavior