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INTRODUCTION: Microtubule-associated tumor suppressor 1 (MTUS1) is a novel tumor suppressor protein involved in cell proliferation, migration, and tumor growth. MTUS1 is thought to be downregulated in various human cancers and associated with poor prognosis. We evaluated the clinicopathologic significance and prognostic value of MTUS1 in colorectal adenocarcinoma. METHODS: Immunohistochemical staining for MTUS1 was performed on tissue microarrays of 393 colorectal adenocarcinoma cases, and MTUS1 staining was classified into high- and low-expression groups. Then, we investigated the correlations between MTUS1 protein expression and various clinicopathological parameters and patient survival. RESULTS: MTUS1 protein was expressed at various grade levels in the cytoplasm of tumor cells, which showed loss or decreased expression of MTUS1. A total of 253 cases (64.4%) were classified into the low MTUS1 protein expression group and 140 cases (35.6%) into the high MTUS1 expression group. A low level of MTUS1 protein significantly correlated with tumor size (p = 0.047), histological grade (p < 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.047), and lymph node metastasis (p < 0.001). Survival analyses showed that patients with low MTUS1 protein expression had worse overall survival (p = 0.007, log-rank test) and worse recurrence-free survival (p = 0.019, log-rank test) than those with high MTUS1 expression. CONCLUSIONS: Low MTUS1 protein expression is associated with adverse clinicopathological characteristics and poor survival outcomes in patients with colorectal adenocarcinoma. These results suggest that MTUS1 functions as a tumor suppressor in colorectal adenocarcinoma and could be a potential prognostic biomarker.

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The vital functions of long non­coding (lnc)RNAs have been verified in gastric carcinoma (GC). However, as a novel cancer­related lncRNA, the influence of leukemia inhibitory factor receptor antisense RNA 1 (LIFR­AS1) in GC cell biological behaviors remains unreported. The present study explored the biological effects of lncRNA LIFR­AS1 on GC progression. Reverse transcription­quantitative PCR was performed to examine lncRNA LIFR­AS1 expression in GC tissues and cells. Cell Counting Kit­8, 5­ethynyl­2'­deoxyuridine incorporation, cell wound healing and Transwell invasion assays were used to assess the functions of lncRNA LIFR­AS1 in GC cell proliferation, migration and invasion. Additionally, associations among lncRNA LIFR­AS1, microRNA (miR)­4698 and microtubule­associated tumor suppressor 1 (MTUS1) were investigated via bioinformatics software and a luciferase reporter system. In addition, western blotting was used to examine the expression of MEK and ERK. Decreased lncRNA LIFR­AS1 expression was observed in GC tissues and cells. Upregulated lncRNA LIFR­AS1 inhibited GC cell proliferation, migration and invasion. Upregulated miR­4698 and downregulated MTUS1 were identified in GC tissues and cells. The inhibitory interaction between lncRNA LIFR­AS1 and miR­4698 was confirmed. Additionally, MTUS1 was predicted as a target gene of miR­4698 positively regulated by lncRNA LIFR­AS1. The MEK/ERK pathway was inhibited by lncRNA LIFR­AS1 via regulating MTUS1. These findings revealed the inhibitory functions of lncRNA LIFR­AS1 in GC cell proliferation, migration and invasion. The process was mediated via miR­4698, MTUS1 and the MEK/ERK pathway.

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Microtubule associated tumor suppressor 1 (MTUS1) has been recognized as a tumor suppressor gene in multiple cancers. However, the molecular mechanisms underlying the regulation of MTUS1 are yet to be investigated. This study aimed to clarify the significance of DNA methylation in silencing MTUS1 expression. We report that MTUS1 acts as tumor suppressor in non-small cell lung carcinoma (NSCLC). Analysis of in silico database and subsequent knockdown of DNMT1 suggested an inverse correlation between DNMT1 and MTUS1 function. Interestingly, increased methylation at MTUS1 promoter is associated with low expression of MTUS1. Treatment with DNA methyltransferases (DNMTs) inhibitor, 5-aza-2'-deoxycytidine (AZA) leads to both reduced promoter methylation accompanied with enrichment of H3K9Ac and enhanced MTUS1 expression. Remarkably, knockdown of MTUS1 showed increased proliferation and migration of NSCLC cells in contrast to diminished proliferation and migration, upon treatment with AZA. We concluded that low expression of MTUS1 correlates to DNA methylation and histone deacetylation in human NSCLC.

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Our previous studies demonstrated that the downregulation of microtubule-associated tumor suppressor 1/angiotensin II type 2 receptor-interacting protein (MTUS1/ATIP) is associated with poor differentiation and prognosis in tongue squamous cell carcinoma (TSCC), and that ATIP1 exerts an antiproliferative effect on TSCC. The aim of the present study was to further investigate the anticancer effect of MTUS1/ATIP3a in TSCC. It was observed that UM1 cells (a TSCC cell line with high migration and invasion ability) exhibited lower expression of ATIP3a compared with UM2 cells (a TSCC cell line with lower migration and invasion ability). Restoration of ATIP3a expression in UM1 cells exerted antiproliferative effects and inhibited migration and invasion, whereas knockdown of ATIP3a promoted proliferation, migration and invasion in UM2 cells. Restoration of ATIP3a expression inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and the expression of Snai2 and vimentin in UM1 cells, whereas knockdown of ATIP3a promoted the phosphorylation of ERK1/2 and the expression of Snai2 and vimentin in UM2 cells. Therefore, MTUS1/ATIP3a was found to suppress the proliferation, migration and invasion of TSCC cells via the ERK1/2-Snai2 pathway.