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Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway.

ABSTRACT: 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.

SUBMITTER: Li W

PROVIDER: S-EPMC7167283 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway.

Li Wei W Li Xiaoqing X Li Xiaoping X Li Mingjiang M Yang Pan P Wang Xuhui X Li Lei L Yang Bo B

OncoTargets and therapy 20200415

<h4>Purpose</h4>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.<h4>Methods</h4>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 corre ...[more]

PMID: 32346296

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Project description:BACKGROUND:The ubiquitin-proteasome pathway, mediated in part, by ubiquitin E3 ligases, is critical in regulating cellular processes such as cell proliferation, apoptosis, and migration. FBXO17 was recently identified as an F-box protein that targets glycogen synthase kinase-3? to the E3 ubiquitin ligase protein complex for polyubiquitination and proteasomal degradation. Here, we identified that in several lung adenocarcinoma cell lines, FBXO17 cellular protein was detected at relatively high levels, as was expression in a subset of lung cancers. Hence, we investigated the effects of FBXO17 on cell proliferation. METHODS:Single cell RNA sequencing analysis was performed on a resection of a non-small cell lung carcinoma tumor to examine FBXO17 expression. Multiple lung cancer cell lines were immunoblotted, and The Cancer Genome Atlas was analyzed to determine if FBXO17 expression was amplified in a subset of lung cancers. A549 cells were transfected with empty vector or FBXO17-V5 plasmid and immunoblotted for Akt pathway mediators including PDK1, ERK1/2, ribosomal protein S6, and CREB. Cell proliferation and viability were analyzed by trypan blue exclusion, BrdU incorporation and an MTS-based fluorometric assay. Studies were also performed after transfecting with sifbxo17. Samples were used in an RNA microarray analysis to evaluate pathways affected by reduced FBXO17 gene expression. RESULTS:We observed that overexpression of FBXO17 increased A549 cell proliferation coupled with Akt activation. Ectopically expressed FBXO17 also increased ERK1/2 kinase activation and increased phosphorylation of RPS6, a downstream target of mTOR. We also observed an increased number of cells in S-phase and increased metabolic activity of lung epithelial cells expressing FBXO17. FBXO17 knockdown reduced Akt Ser 473 phosphorylation approaching statistical significance with no effect on Thr 308. However, ERK1/2 phosphorylation, cellular metabolic activity, and overall cell numbers were reduced. When we analyzed RNA profiles of A549 cells with reduced FBXO17 expression, we observed downregulation of several genes associated with cell proliferation and metabolism. CONCLUSIONS:These data support a role for FBXO17 abundance, when left unchecked, in regulating cell proliferation and survival through modulation of Akt and ERK kinase activation. The data raise a potential role for the F-box subunit in modulating tumorigenesis.

Dataset Information

Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway.

Publications

Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway.

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