The Regulatory Role of Both MBNL1 and MBNL1-AS1 in Several Common
Cancers

Zhang, Qi; Wu, Yinxin; Chen, Jinlan; Cai, Yuxuan; Wang, Bei; Tan, Fangshun; Mou, Jie; Yuan, Chengfu

doi:10.2174/1381612827666210830110732

Cited by 17 publications

(12 citation statements)

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“…MBNL1, a tissue-specific RNA metabolism regulator, was an important regulator of tumor metastasis and growth. High MBNL1 expression level in human breast tumors was found to be associated with reduced metastatic relapse likelihood and survival and promote tumor progression [ 51 , 52 ]. MBNL1 could act as major regulator in monocyte-to-macrophage differentiation and activation, and regulate immune infiltration [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

ARHGAP39 is a prognostic biomarker involved in immune infiltration in breast cancer

Yao

et al. 2023

BMC Cancer

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Background Current studies on the role of ARHGAP39 mainly focused on its effect on neurodevelopment. However, there are few studies on the comprehensive analysis of ARHGAP39 in breast cancer. Methods ARHGAP39 expression level was analyzed based on the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database and validated by qPCR in various cell lines and tumor tissues. The prognostic value was analyzed using Kaplan–Meier curve analysis. CCK-8 and transwell assays were conducted to identify the biological function of ARHGAP39 in tumorigenesis. Signaling pathways related to ARHGAP39 expression were identified by the GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA). The correlations between ARHGAP39 and cancer immune infiltrates were investigated via TIMER, CIBERSORT, ESTIMATE and tumor-immune system interactions database (TISIDB). Results ARHGAP39 was overexpressed in breast cancer and associated with poor survival outcomes. In vitro experiments revealed that ARHGAP39 could facilitate the proliferation, migration, and invasion capability of breast cancer cells. GSEA analysis showed that the main enrichment pathways of ARHGAP39 was immunity-related pathways. Considering the immune infiltration level, ARHGAP39 was negatively associated with infiltrating levels of CD8 + T cell and macrophage, and positively associated with CD4 + T cell. Furthermore, ARHGAP39 was significantly negatively correlated with immune score, stromal score, and ESTIMATE score. Conclusions Our findings suggested that ARHGAP39 can be used as a potential therapeutic target and prognostic biomarker in breast cancer. ARHGAP39 was indeed a determinant factor of immune infiltration.

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Section: Discussionmentioning

confidence: 99%

ARHGAP39 is a prognostic biomarker involved in immune infiltration in breast cancer

Yao

et al. 2023

BMC Cancer

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“…Of note, PTBP1 has been linked to colorectal cancer [26], a disease closely related to PMP. Similarly, MBNL1 is a well-known player in oncogenesis [27], such as in digestive system tumors [28].…”

Section: Discussionmentioning

confidence: 99%

A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival

Moreno-Montilla

Alors‐Perez

Martínez-López³

et al. 2022

Preprint

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Purpose: Pseudomyxoma peritonei (PMP) is a rare cancer that causes chronic and uncontrollable mucus accumulation, gradually leading to intraperitoneal organ adhesion, bowel obstruction, malnutrition, and eventually cachexia and death. Aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy offer the best results; but the probability of relapse remains high. The study of the distinct molecular layers underlying PMP is essential to understand its genesis and progression. Alternative splicing is emerging as a new player in all cancers, but its role in PMP is unknown. The aim of this work was to assess the splicing machinery status in PMP and determine its potential contribution to disease prognosis. Methods: A set of 62 splicing-related genes were evaluated in a cohort of 29 patients using a microfluidic array, and their levels were compared between tumor and non-tumor tissue and correlated to relevant clinical parameters. Selected components were validated by immunohistochemistry and subsequently studied in detail by enrichment analyses. Results: Results revealed a profound dysregulation of the splicing machinery at RNA/protein level, which allowed to distinguish between tumor and control tissues. Particularly, the splicing factors HNRNPK, MBNL1, PTBP1 and RAVER1were associated with poor prognosis and their expression was linked to TP53regulation and inflammation processes. Conclusions: These findings provide the first evidence for the dysregulation of the splicing machinery in PMP, suggesting that it could be functionally altered and play a role in this rare malignant disease. Therefore, its detailed understanding could help to identify novel prognostic biomarkers and therapeutic targets in PMP.

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“… 5 - 10 Notably, Muscleblind-like 1 (MBNL1) is significantly downregulated in various cancers, such as gastric cancer, breast cancer, glioma, and leukemia. 11 Similarly, changes in the expression of the quaking (QKI) protein have been observed in lung, colon, gastric, and prostate cancer. 12 - 15 Numerous studies have proposed that both MBNL1 and QKI function as tumor suppressors in specific cancers.…”

Section: Introductionmentioning

confidence: 95%

Involvement of circRNA Regulators MBNL1 and QKI in the Progression of Esophageal Squamous Cell Carcinoma

Wang,

Zhou,

Zhang

et al. 2024

Cancer Control

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Objectives To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. Background MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production – an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. Methods The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. Results ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. Conclusions This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.

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The Regulatory Role of Both MBNL1 and MBNL1-AS1 in Several Common Cancers

Cited by 17 publications

References 0 publications

ARHGAP39 is a prognostic biomarker involved in immune infiltration in breast cancer

ARHGAP39 is a prognostic biomarker involved in immune infiltration in breast cancer

A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival

Involvement of circRNA Regulators MBNL1 and QKI in the Progression of Esophageal Squamous Cell Carcinoma

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