ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation

Qiu, Bai‐Quan; Lin, Xiahui; Lai, Songqing; Lü, Feng; Lin, Kun; Long, Xiang; Zhu, Shu‐Qiang; Zou, Hua-Xi; Xu, Jianjun; Liu, Jichun; Wu, Yuanyi

doi:10.1186/s12935-021-02380-2

Cited by 11 publications

(11 citation statements)

References 86 publications

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“…ITGB1-DT was associated with T stage, treatment effect, DSS, and PFI and was an independent risk factor for poor prognosis, suggesting that ITGB1-DT could be a prognostic biomarker for STAD. I T G B 1 -D T p l a y s a n i m p o r t a n t r o l e i n l u n g adenocarcinoma, and it has been reported that interference with ITGB1-DT induces the growth and migration of lung adenocarcinoma cells (8,9). Using the GO analysis, we found that interference with ITGB1-DT expression was related to cell growth.…”

Section: Discussionmentioning

confidence: 78%

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Inhibition of ITGB1-DT expression delays the growth and migration of stomach adenocarcinoma and improves the prognosis of cancer patients using the bioinformatics and cell model analysis

Ni¹,

Guo²,

Luo³

2022

J Gastrointest Oncol

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Background: The long non-coding RNA, integrin subunit beta 1 (ITGB1) divergent transcript (ITGB1-DT), is known to be involved in cancer progression and associated with the poor prognosis of cancer patients. At present, the role of ITGB1-DT in stomach adenocarcinoma (STAD) has not been reported. Methods:The expression level of ITGB1-DT was detected in normal gastric and STAD tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. A receiver operating characteristic (ROC) analysis was used to evaluate the role of ITGB1-DT in diagnosing STAD. The relationship between ITGB1-DT overexpression and clinicopathological features, prognosis, and immuneinfiltrated cells in STAD were explored using correlation, survival, and Cox regression analyses. A cell model of ITGB1-DT interference was constructed to explore the roles of ITGB1-DT on STAD cell proliferation and migration, and the signaling mechanism was investigated using Gene Set Enrichment Analysis (GSEA).Results: ITGB1-DT was expressed up-regulated in STAD tissues. ITGB1-DT overexpression was associated with the T stage, therapeutic effect, overall survival, progression-free interval status, and poor prognosis in STAD patients. ITGB1-DT overexpression was valuable in diagnosing STAD and a negative factor affecting the prognosis of STAD patients. Interference with ITGB1-DT expression inhibited STAD cell proliferation, invasion, and migration. GSEA results showed that ITGB1-DT may be involved in STAD progression through the insulin, p53, mechanistic target of rapamycin kinase (MTOR), and other signaling pathways. Overexpression of ITGB1-DT was significantly correlated with the levels of STAD B cells, T cells, T helper cells, CD8 T cells, cytotoxic cells, and other immune cells.Conclusions: ITGB1-DT was overexpressed and associated with poor prognosis in STAD. Interference with ITGB1-DT expression may delay the progression of STAD to improve the prognosis of STAD patients.

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Section: Discussionmentioning

confidence: 78%

“…The ITGB1-DT/ITGB1/ Wnt/β-catenin/MYC positive feedback loop was involved in lung adenocarcinoma progression (8). ITGB1-DT/ ARNTL2 promoted the growth and migration of lung adenocarcinoma cells, whereas miR-30b-3p reversed ITGB1/ARNTL2-mediated carcinogenesis (9). Currently, the mechanism of ITGB1-DT in STAD has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of ITGB1-DT expression delays the growth and migration of stomach adenocarcinoma and improves the prognosis of cancer patients using the bioinformatics and cell model analysis

Ni¹,

Guo²,

Luo³

2022

J Gastrointest Oncol

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“…etc. In our previous study, bioinformatics analysis showed that the ITGB1-DT/ARNTL2 axis induces lung adenocarcinoma progression [ 60 ], suggesting the important role of bioinformatics. Moreover, the application of bioinformatic analysis can enhance our understanding of research at the molecular level [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

circRanGAP1/miR-27b-3p/NRAS Axis may promote the progression of hepatocellular Carcinoma

et al. 2022

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Background Though circular RNAs (circRNAs) are the key regulators in tumor carcinogenesis, they remain largely unexplored in hepatocellular carcinoma (HCC). Methods The expression of RanGAP1-derived circRNAs (circ_0063531, circ_0063534, circ_0063513, circ_0063518, circ_0063507, circ_0063723) were evaluated in eight paired HCC and normal tissues, and the correlation between circRanGAP1 (circ_0063531) expression and clinicopathological characteristics in 40 HCC patients was determined. The association between miR-27b-3p and circRanGAP1 or NRAS was predicted using bioinformatics analysis. The expression of circRanGAP1, miR-27b-3p, and NRAS were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The potential oncogenic role of circ-RanGAP1 was assessed using CCK-8, colony formation, transwell assays in vitro, subcutaneous tumor mouse model, vein tail metastatic model, and orthotopically implanted intrahepatic HCC model in vivo. Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to explore the binding site between miR-27b-3p and circ-RanGAP1 or NRAS. Protein expression was detected using western blotting. The localization of miR-27b-3p and circ-RanGAP1 was investigated using fluorescence in situ hybridization (FISH). The level of immune infiltration was assessed by bioinformatics analysis, flow cytometry, and orthotopically implanted intrahepatic HCC models. Results Here, we found elevated circRanGAP1 in the cells and clinical tissues of patients with HCC. Increased circRanGAP1 levels are associated with enlarged tumors and the advanced stage of TNM. CircRanGAP1 promotes the growth, migration, and HCC cell invasion, concurrently with the growth and metastasis of tumors in-vivo. Moreover, circRanGAP1 is mainly located inside the cytoplasm. Mechanistically, circRanGAP1 as an oncogene promotes HCC progression by miR-27b-3p/NRAS/ERK axis, furthermore, affects the infiltration level of tumor-associated macrophages probably by sponging miR-27b-3p. Immune infiltration analysis shows that NRAS is positively correlated with the levels of CD68+ tumor-associated macrophages in HCC samples and that NRAS and CD68 are related to the poor outcome of HCC. Conclusion These results reveal that circRanGAP1 is a HCC oncogene that function by the miR-27b-3p/NRAS/ERK axis and regulates the infiltration levels of tumor-associated macrophages by sponging miR-27b-3p. Therefore, circRANGAP1/ NRAS axis may be an important potential treatment target against HCC.

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“…Integrins were α/β heterodimeric cell surface receptors that play a key role in cell adhesion ( 16 ) and migration ( 17 , 18 ) as well as growth and survival ( 19 , 20 ). The beta-1 subfamily includes 12 unique integrin proteins that bind different extracellular matrix molecules, control extracellular integrin binding, and affect cell adhesion or migration ( 21 , 22 ). Meanwhile, intracellular signal transduction information transcribed from the cytoplasmic tail domain of beta-1 cells contributes to the regulation of cell proliferation ( 23 , 24 ), cytoskeletal reorganization, and gene expression ( 25 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

ITGB1-mediated molecular landscape and cuproptosis phenotype induced the worse prognosis in diffuse gastric cancer

Zhu

Chen

Han³

et al. 2023

Front. Oncol.

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Diffuse type gastric cancer was identified with relatively worse prognosis than other Lauren’s histological classification. Integrin β1 (ITGB1) was a member of integrin family which played a markedly important role in tumorigenesis and progression. However, the influence of ITGB1 in diffuse gastric cancer (DGC) remains uncertain. Here, we leveraged the transcriptomic and proteomic data to explore the association between ITGB1 expression and clinicopathologic information and biological process in DGC. Cell phenotype experiments combined with quantitative-PCR (q-PCR) and western blotting were utilized to identify the potential molecular mechanism underling ITGB1.Transcriptomics and proteomics both revealed that the higher ITGB1 expression was significantly associated with worse prognosis in DGC, but not in intestinal GC. Genomic analysis indicated that the mutation frequency of significantly mutated genes of ARID1A and COL11A1, and mutational signatures of SBS6 and SBS15 were markedly increased in the ITGB1 low expression subgroup. The enrichment analysis revealed diverse pathways related to dysregulation of ITGB1 in DGC, especially in cell adhesion, proliferation, metabolism reprogramming, and immune regulation alterations. Elevated activities of kinase-ROCK1, PKACA/PRKACA and AKT1 were observed in the ITGB1 high-expression subgroup. The ssGSEA analysis also found that ITGB1 low-expression had a higher cuproptosis score and was negatively correlated with key regulators of cuproptosis, including FDX1, DLAT, and DLST. We further observed that the upregulated expression of mitochondrial tricarboxylic acid (TCA) cycle in the ITGB1 low-expression group. Reduced expression of ITGB1 inhibited the ability of cell proliferation and motility and also potentiated the cell sensitive to copper ionophores via western blotting assay. Overall, this study revealed that ITGB1 was a protumorigenic gene and regulated tumor metabolism and cuproptosis in DGC.

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ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation

Cited by 11 publications

References 86 publications

Inhibition of ITGB1-DT expression delays the growth and migration of stomach adenocarcinoma and improves the prognosis of cancer patients using the bioinformatics and cell model analysis

Inhibition of ITGB1-DT expression delays the growth and migration of stomach adenocarcinoma and improves the prognosis of cancer patients using the bioinformatics and cell model analysis

circRanGAP1/miR-27b-3p/NRAS Axis may promote the progression of hepatocellular Carcinoma

ITGB1-mediated molecular landscape and cuproptosis phenotype induced the worse prognosis in diffuse gastric cancer

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