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Oncogenic role of abnormal spindle‑like microcephaly‑associated protein in lung adenocarcinoma.

ABSTRACT: Lung adenocarcinoma (LUAD) is a common malignant cancer worldwide. It is urgent to explore its underlying molecular mechanism and identify novel diagnostic biomarkers. Abnormal spindle‑like microcephaly (ASPM) has recently received considerable attention due to its function in tumor progression. However, its role in LUAD is unclear. The present study aimed to explore the clinical role of ASPM in LUAD. Seven pairs of LUAD and adjacent normal tissues were collected to identify potential LUAD biomarkers using transcriptome sequencing. The association between ASPM expression and LUAD progression was evaluated using bioinformatics analysis and data obtained from clinical specimens. Using small interfering RNA technology, the function of ASPM was analyzed in the LUAD H1299 and A549 cell lines. Transcriptional profiling of ASPM‑deficient H1299 cells was then performed to determine the downstream targets of ASPM. Using databases and clinical specimens, it was revealed that ASPM expression was frequently elevated in LUAD tissues, and this upregulation was highly associated with LUAD progression. ASPM served as an oncogenic regulator of LUAD cell proliferation and metastasis. Mechanistically, ASPM facilitated epithelial‑mesenchymal transition (EMT) via the PI3K/AKT signaling pathway and 740 Y‑P, an activator of this pathway, restored the migratory ability of ASPM‑knockdown LUAD cells. The current study identified ASPM as an independent prognostic biomarker of LUAD that served an important oncogenic role in regulating LUAD cell metastasis by promoting EMT via the PI3K/AKT signaling pathway. Targeting ASPM may therefore be a therapeutic strategy for treating LUAD.

SUBMITTER: Wang J

PROVIDER: S-EPMC8012022 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLung cancer is one of the most common cancer worldwide, invasion and metastasis are still the bottleneck in the clinical setting. More diagnostic markers and drug targets need to be clarified. Therefore, we screened abnormal spindle-like microcephaly-associated protein (ASPM) as our candidate gene, which is associated with the poor prognosis. The aim of the present study was to understand the roles of ASPM in cell invasion in non-small cell lung cancer (NSCLC).MethodsGene Expression Omnibus (GEO) datamining was used to identify ASPM. Transwell invasion assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to discover the molecular functions of ASPM. Overexpression and small interfering mediated knockdown techniques have been used to study the cell invasion hallmarks of cancer.ResultsASPM stood out among all the candidate genes from GEO datamining. ASPM in lung cancer tissues has been associated with poor overall survival rate. The protein levels of ASPM has been validated using lung cancer patients' tissues, which upregulation of ASPM expression has been found in lung cancer patients. Silencing of ASPM decreased the cell invasion reflected by epithelial-mesenchymal transition (EMT) biomarkers: downregulation of vimentin and upregulation of E-cadherin. Matrix metalloproteinase (MMP) 2/9 protein levels were also affected upon transient knockdown of ASPM. Furthermore, the suppression of ASPM markedly inhibited the Wnt/β-catenin signaling pathway in vitro. The ectopic expression of ASPM had the opposite effect. The inhibition of β-catenin in ASPM-overexpressing lung cancer cells reduced the expression of EMT markers. The inhibitory effects on the Wnt/β-catenin signaling pathway were attenuated in cancer cells when ASPM was silenced. These findings demonstrated that the silencing of ASPM strongly reduced cell invasion in lung cancer.ConclusionsASPM promoted NSCLC invasion through EMT and by affecting the MMP family of proteins. The Wnt/β-catenin signaling pathway played an indispensable role in the ASPM-mediated NSCLC EMT-invasion cascade.

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Oncogenic role of abnormal spindle‑like microcephaly‑associated protein in lung adenocarcinoma.

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