Dataset Information

MiR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.

ABSTRACT: Forkhead box D1 (FOXD1) belongs to the FOX protein family, which has been found to function as a oncogene in multiple cancer types, but its role in head and neck squamous cell carcinoma (HNSCC) requires further investigation. Our research aimed to investigate the function of FOXD1 in HNSCC. Bioinformatics analysis indicated that mRNA level of FOXD1 was highly expressed in HNSCC tissues, and over-expressed FOXD1 was related to poor prognosis. Moreover, FOXD1 knockdown increased the ratio of senescent cells but decreased the proliferation ability, while FOXD1 overexpression obtained the opposite results. In vitro experiments revealed that FOXD1 bound to the p21 promoter and inhibited its transcription, which blocked the cyclin dependent kinase 2 (CDK2)/retinoblastoma (Rb) signaling pathway, thus preventing senescence and accelerating proliferation of tumor cells. CDK2 inhibitor could reverse the process to some extent. Further research has shown that miR-3oe-5p serves as a tumor suppressant by repressing the translation of FOXD1 through combining with the 3'-untranslated region (UTR). Thus, FOXD1 resists cellular senescence and facilitates HNSCC cell proliferation by affecting the expression of p21/CDK2/Rb signaling, suggesting that FOXD1 may be a potential curative target for HNSCC.

SUBMITTER: Wu T

PROVIDER: S-EPMC10415393 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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miR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.

Wu Tong T Yang Zhongyuan Z Chen Weichao W Jiang Mingjie M Xiao Zhichao Z Su Xuan X Jiao Zan Z Yu Yongchao Y Chen Shuwei S Song Ming M Yang Ankui A

Cell death discovery 20230810 1

Forkhead box D1 (FOXD1) belongs to the FOX protein family, which has been found to function as a oncogene in multiple cancer types, but its role in head and neck squamous cell carcinoma (HNSCC) requires further investigation. Our research aimed to investigate the function of FOXD1 in HNSCC. Bioinformatics analysis indicated that mRNA level of FOXD1 was highly expressed in HNSCC tissues, and over-expressed FOXD1 was related to poor prognosis. Moreover, FOXD1 knockdown increased the ratio of senes ...[more]

PMID: 37563111

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Project description:Forkhead box D1 (FOXD1) is a new member of FOX transcription factor family. FOXD1 has demonstrated multilevel roles during normal development, and several diseases' pathogenesis. However, little is known about the role of FOXD1 in the progression of head and neck squamous cancer (HNSC). In the present study, we analyzed FOXD1 expression pattern using The Cancer Genome Atlas (TCGA) dataset, Gene Expression Omnibus (GEO) datasets, HNSC cell lines, and HNSC tissues. Then, we analyzed the correlation between FOXD1 expression and clinical characteristics, and evaluated the prognostic value of FOXD1 in HNSC. Moreover, we assessed the relationship between FOXD1 expression and tumor microenvironment (TME) and immune cell infiltration using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) algorithms. Finally, we predicted the FOXD1-related biological processes (BPs) and signal pathways. FOXD1 was up-regulated in HNSC tissues in TCGA datasets, validated by GEO datasets, HNSC cell lines and HNSC tissues. FOXD1 expression was significantly associated with tumor site and HPV infection. Univariate and multivariate Cox regression analyses showed that FOXD1 expression was an independent prognostic factor. Moreover, we found that the proportions of naïve B cells, plasma cells, and resting dendritic cells (DCs) were negatively correlated with FOXD1 expression, otherwise, the proportion of activated mast cells was positively correlated with FOXD1 expression using CIBERSORT algorithm. Gene Set Enrichment Analyses (GSEAs) revealed that FOXD1 was mainly involved in cancer-related signaling pathway and metabolism-related pathways. FOXD1 was a potential oncogene, and might represent an indicator for predicting overall survival (OS) of HNSC patients. Moreover, many cancer-related pathways and metabolism-related processes may be regulated by FOXD1.

Dataset Information

MiR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.

Publications

miR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.

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