Dataset Information

FGFR1 regulates proliferation and metastasis by targeting CCND1 in FGFR1 amplified lung cancer.

ABSTRACT: Aims: The analysis of the online databases revealed that CCND1 expression is correlated with poor prognosis in LSCC. We aimed to explore the function of CCND1 in tumor progression in LSCC.Main methods: The expression of mRNA was measured using qRT-PCR. Protein expression was assessed by Western blot. Cell migration and invasion were assessed by transwell assay.Key findings: CCND1 was co-overexpressed with FGFR1 in lung cancer patients. Overexpression of CCND1 promoted LSCC cell proliferation and metastasis. FGFR1 promoted the processes of EMT through AKT/MAPK signaling by targeting CCND1 in FGFR1-amplification cell lines.Significance: IIn conclusion, our study demonstrated the regulatory mechanism between CCND1 and FGFR1 in FGFR1 amplified LSCC. Co-targeting CCND1 and FGFR1 could provide greater clinical benefits.

SUBMITTER: Yang Y

PROVIDER: S-EPMC7250189 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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FGFR1 regulates proliferation and metastasis by targeting CCND1 in FGFR1 amplified lung cancer.

Yang Ying Y Lu Tingting T Li Ziming Z Lu Shun S

Cell adhesion & migration 20201201 1

Aims: The analysis of the online databases revealed that CCND1 expression is correlated with poor prognosis in LSCC. We aimed to explore the function of CCND1 in tumor progression in LSCC.Main methods: The expression of mRNA was measured using qRT-PCR. Protein expression was assessed by Western blot. Cell migration and invasion were assessed by transwell assay.Key findings: CCND1 was co-overexpressed with FGFR1 in lung cancer patients. Overexpression of CCND1 promoted LSCC c ...[more]

PMID: 32380883

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Project description:ObjectiveThis study aimed to describe the mechanism of exosome-derived miR-486-5p underlying the cell cycle and progression in lung adenocarcinoma (LUAD).MethodsBioinformatics methods were applied for identifying the differentially expressed genes (DEGs) in the GEO-LUAD dataset, predicting where the potential target miRNA was expressed and exploring the corresponding downstream target mRNA. qRT-PCR was conducted to detect the levels of the target genes in cancer cells. Thereafter, a series of in vitro experiments were performed for cell activities evaluation, including CCK-8, EdU, colony formation assay and transwell. Besides, Western blot was applied to determine the protein levels of the migration and invasion-related factors (NEK2, E-cadherin, N-cadherin, Vimentin, MMP-2, and MMP-9). Dual-luciferase reporter gene assay was employed for validating the targeted relationship between the target genes. Furthermore, nude mouse transplantation tumor experiment was conducted to further validate the role of the target miRNA in tumor development, and immunohistochemistry was used for Ki67 detection and TUNEL was applied for cell apoptosis assay.ResultsmiR-486-5p was observed to be enriched in serum exosomes, and seen to be significantly down-regulated in cancer tissues as well as in cancer serum exosomes. It was proven that exosomes could release miR-486-5p, thus regulating LUAD progression and affecting cell cycle. Moreover, NEK2 was identified as a target of miR-486-5p both in vivo and in vitro. Enrichment analysis revealed that NEK2 was mainly activated in cell cycle and mitosis-related pathways. Meanwhile, NEK2 was found to present significant difference in different TNM stages. Furthermore, rescue experiments indicated that the inhibitory effect of miR-486-5p overexpression on LUAD progression could be abrogated when miR-486-5p and NEK2 were simultaneously up-regulated.ConclusionExosome-derived miR-486-5p is responsible for cell cycle arrest as well as the inhibition of cell proliferation and metastasis in LUAD via targeting NEK2.

Dataset Information

FGFR1 regulates proliferation and metastasis by targeting CCND1 in FGFR1 amplified lung cancer.

Publications

FGFR1 regulates proliferation and metastasis by targeting CCND1 in FGFR1 amplified lung cancer.

Similar Datasets

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