Dataset Information

TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer.

ABSTRACT: BACKGROUND Metastasis contributes to the high mortality rate of non-small cell lung cancer (NSCLC), and gaining a better understanding of its metastatic mechanisms would aid in initiating effective clinical treatment. MATERIAL AND METHODS In this study, bioinformatics analyses of the GEO database and TCGA-LUAD were first used to identify the key node gene regulating NSCLC malignant progression. Further in vitro experiments, including wound healing assay, invasion assay, Western blot assay, and luciferase report assay, were used to clarify the functions and mechanism of TPX2 in NSCLC. RESULTS Results of the TCGA analysis showed that TPX2 was significantly positively correlated with tumor metastasis and growth and the clinical stage of NSCLC. In addition, high levels of TPX2 significantly indicated a poor survival rate. In vitro experimental results also revealed that the upregulation of TPX2 significantly promoted NSCLC cell migration and invasion and could affect cell replasticity. Further results indicated that TPX2 significantly activated the epithelial-mesenchymal transition process and promoted the expression and activities of matrix metalloproteinase (MMP)2 and MMP9. CONCLUSIONS This study demonstrated that TPX2 promotes the metastasis and malignant progression of NSCLC and could thus serve as a marker of poor prognosis in NSCLC.

SUBMITTER: Zhou F

PROVIDER: S-EPMC7427348 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer.

Zhou Fang F Wang Meng M Aibaidula Mijiti M Zhang Zhiguo Z Aihemaiti Abudusaimaiti A Aili Rezhake R Chen Hao H Dong Shuangfeng S Wei Wei W Maimaitiaili Abulizi A

Medical science monitor : international medical journal of experimental and clinical research 20200804

BACKGROUND Metastasis contributes to the high mortality rate of non-small cell lung cancer (NSCLC), and gaining a better understanding of its metastatic mechanisms would aid in initiating effective clinical treatment. MATERIAL AND METHODS In this study, bioinformatics analyses of the GEO database and TCGA-LUAD were first used to identify the key node gene regulating NSCLC malignant progression. Further in vitro experiments, including wound healing assay, invasion assay, Western blot assay, and l ...[more]

PMID: 32748897

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Project description:BackgroundRecent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its' molecular mechanisms controlling cancer cell migration and metastasis are unclear.MethodsExpression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry.ResultsBANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression.ConclusionWe determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.

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TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer.

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TPX2 Promotes Metastasis and Serves as a Marker of Poor Prognosis in Non-Small Cell Lung Cancer.

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