Dataset Information

FAM110B Inhibits Non-Small Cell Lung Cancer Cell Proliferation and Invasion Through Inactivating Wnt/?-Catenin Signaling.

ABSTRACT: Purpose:FAM110B is a member of the FAM110 family (family with sequence similarity 110), which is a component of the centrosome associated proteins. Previous studies have shown that FAM110B may be involved in the process of cell cycle and may play a role in carcinogenesis and tumor progression. Using an online database, we found that FAM110B may predict favorable prognosis in non-small cell lung cancer (NSCLC). Therefore, the role of FAM110B playing in NSCLC needs to be further investigated. Patients and Methods:Online databases and immunohistochemistry were used to predict the expression and prognostic value of FAM110B in NSCLC samples. Immunofluorescence staining was used to investigate the subcellular distribution of FAM110B. Western blot, MTT, colony formation, and matrigel invasion assay were used to detect the expression and the effect of FAM110B on mediating proliferation and invasion in NSCLC cell lines. Results:In this study, immunohistochemistry results showed that FAM110B expression significantly correlated with early TNM staging (P=0.020) and negative regional lymph node metastasis (P=0.006). Kaplan-Meier survival analysis found that the median survival time of patients with positive FAM110B expression (56.181±2.348 months) was significantly longer than those with negative FAM110B expression (47.701±2.997 months, P=0.024). Moreover, overexpression of FAM110B inhibited the proliferation and invasion of A549, H1299, and LK2 cell lines. Conversely, FAM110B RNAi exerted opposite effects in the above cell lines. Furthermore, FAM110B overexpression downregulated the active ?-catenin, phosphorylation of GSK-3? (p-GSK-3?), cyclin B1, cyclin D1, MMP2, and MMP7, and upregulated the phosphorylation of ?-catenin (p-?-catenin) in A549 and H1299 cells. Besides, the FAM110B-induced depressions of p-GSK-3? and active ?-catenin were reversed after being treated with Wnt/?-catenin inhibitor, XAV-939. Conclusion:In summary, our results demonstrated that the overexpression of FAM110B restricts the proliferation and invasion of NSCLC cells by inhibiting Wnt/?-catenin signaling. Our study reveals the antitumor function of FAM110B in NSCLC and indicates that FAM110B is a potential therapeutic target.

SUBMITTER: Xie M

PROVIDER: S-EPMC7245470 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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FAM110B Inhibits Non-Small Cell Lung Cancer Cell Proliferation and Invasion Through Inactivating Wnt/β-Catenin Signaling.

Xie Menghua M Cai Lin L Li Jingduo J Zhao Jing J Guo Yingxue Y Hou Zaiyu Z Zhang Xiupeng X Tian Hua H Li Ailin A Miao Yuan Y

OncoTargets and therapy 20200519

<h4>Purpose</h4>FAM110B is a member of the FAM110 family (family with sequence similarity 110), which is a component of the centrosome associated proteins. Previous studies have shown that FAM110B may be involved in the process of cell cycle and may play a role in carcinogenesis and tumor progression. Using an online database, we found that FAM110B may predict favorable prognosis in non-small cell lung cancer (NSCLC). Therefore, the role of FAM110B playing in NSCLC needs to be further investigat ...[more]

PMID: 32547070

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Project description:BackgroundLong non-coding RNAs (lncRNAs) are pervasively transcribed in genome and emerging as a new player in tumorigenesis due to their functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. As the most frequent malignancy and the foremost source of cancer mortality, lung cancer is a heterogeneous disorder. The most common type of lung cancer is Non-small cell lung cancer (NSCLC), occupying 85% of the total cases, and the main subtypes of NSCLC include lung adenocarcinoma (LAD), large cell carcinoma (LCC), and lung squamous cell carcinoma (LSCC). Recently, numerous lncRNAs have been reported to be strongly linked to NSCLC. In the present study, we found that a new lncRNA CBR3-AS1 is highly expressed in lung cancer. In addition, we also examined the expression of lncRNA CBR3-AS1 in 60 of LADs, 40 of LCCs and 40 of LSCCs patient samples, finding that CBR3-AS1 was specificity highly expressed in LAD cancer tissues. Mechanically, we discovered that CBR3-AS1 could regulate the proliferation, migration and invasion of LAD cells through targeting Wnt/?-catenin signaling.MethodsReal-time PCR, RNA-pulldown, RIP, western blotting, lentivirus transfection, luciferase reporter assays, cell proliferation assays, colony formation assays, wound healing scratch assays and transwell assays were employed to examine the relationship between lncRNA CBR3-AS1 and its regulation of Wnt/?-catenin signaling in LAD cells.ResultsLncRNA CBR3-AS1 is highly-expressed in LAD and cell lines. LncRNA CBR3-AS1 shows physical association with ?-catenin. CBR3-AS1 could facilitate Wnt/?-catenin signaling activation thought promoting nuclear localization of ?-catenin. CBR3-AS1 promotes LAD cell proliferation, migration and invasion by targeting Wnt/?-catenin signaling.ConclusionIt can be found that a new functional lncRNA CBR3-AS1 could promote nuclear localization of ?-catenin so as to facilitate Wnt/?-catenin signaling activation and regulate the proliferation, migration and invasion of LAD cells.

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FAM110B Inhibits Non-Small Cell Lung Cancer Cell Proliferation and Invasion Through Inactivating Wnt/?-Catenin Signaling.

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FAM110B Inhibits Non-Small Cell Lung Cancer Cell Proliferation and Invasion Through Inactivating Wnt/β-Catenin Signaling.

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