Dataset Information

FOXM1 Promotes Malignant Proliferation of Esophageal Squamous Cell Carcinoma Through Transcriptional Activating CDC6.

ABSTRACT: Forkhead box M1 (FOXM1) is a proliferative transcription factor and plays a vital role in many cancers. However, the function and molecular mechanism of FOXM1 in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Hence, we aim to clarify the molecular basis of FOXM1-mediated ESCC progression. In this study, bioinformatics analysis showed that FOXM1 was mainly involved in key signal pathways, including cell proliferation, cell cycle, and homologous recombination in ESCC, and predicted that CDC6 might be a potential regulatory target gene of FOXM1. The results revealed that FOXM1 and CDC6 were significantly overexpressed in ESCC tissue and cell line, and their expression was positively correlated. Further studies showed that FOXM1 directly transcriptionally activated CDC6 by binding to its promoter region in ESCC cells. Moreover, FOXM1 mediated ESCC cell proliferation by regulating CDC6 expression, which may be related to promoting G1-S phase transition of cell cycle. Taken together, FOXM1-CDC6 axis mediates ESCC malignant proliferation and may serve as a potential biological target for ESCC treatment.

SUBMITTER: Chen X

PROVIDER: S-EPMC9293688 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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FOXM1 Promotes Malignant Proliferation of Esophageal Squamous Cell Carcinoma Through Transcriptional Activating CDC6.

Chen Xiongfeng X Chen Jingbo J Yu Xunbin X Lin Guishan G Chen Ting T

DNA and cell biology 20220530 7

Forkhead box M1 (FOXM1) is a proliferative transcription factor and plays a vital role in many cancers. However, the function and molecular mechanism of FOXM1 in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Hence, we aim to clarify the molecular basis of FOXM1-mediated ESCC progression. In this study, bioinformatics analysis showed that FOXM1 was mainly involved in key signal pathways, including cell proliferation, cell cycle, and homologous recombination in ESCC, and pred ...[more]

PMID: 35639418

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Project description:The aim of the present study was to examine the function of transgelin (TAGLN) and its underlying mechanism in the ferroptosis of esophageal squamous cell carcinoma (ESCC) cells. To meet this aim, the association between TAGLN expression and the prognosis of patients with ESCC was determined using tissue samples and clinical data. Gene Expression Omnibus databank and Gene Set Enrichment Analysis data were used to examine which genes were co‑expressed with TAGLN, as well as the influence of TAGLN on ESCC. Subsequently, Transwell chamber, wound healing, Cell Counting Kit‑8 viability and colony formation assays were performed to observe the effects of TAGLN on the migration, invasion, viability and proliferation of Eca‑109 and KYSE‑150 cells. The interaction between TAGLN and p53 in the regulation of ferroptosis was detected using reverse transcription‑quantitative PCR, co‑immunoprecipitation and fluorescence co‑localization assays, and a xenograft tumor model was established to examine the effect of TAGLN on tumor growth. The level of TAGLN expression in patients with ESCC was found to be low, compared with normal esophageal tissue, and a positive association was identified between the prognosis of ESCC and TAGLN expression. The expression of the ferroptosis marker protein, glutathione peroxidase 4, was found to be high, whereas that of acyl‑CoA synthetase long‑chain family member 4 was lower in patients with ESCC compared with expression levels in healthy patients. The overexpression of TAGLN resulted in a significant decrease in the invasive and proliferative capabilities of Eca‑109 and KYSE‑150 cells in vitro compared with the control group; in vivo, TAGLN overexpression was found to significantly decrease tumor size, volume and weight after one month of growth. In addition, the proliferation, migration and invasion of Eca‑109 cells in vivo was stimulated by the knockdown of TAGLN. The results of the transcriptome analysis further demonstrated that TAGLN was able to induce ferroptosis‑associated cell functions and pathways. Finally, TAGLN overexpression was found to promote ferroptosis in ESCC through its interaction with p53. Taken together, the findings of the present study suggested that the malignant development of ESCC may be inhibited by TAGLN through the manifestation of ferroptosis.

Project description:Esophageal squamous cell carcinoma (ESCC) is a malignant upper digestive tract cancer, and its pathogenesis and etiology are poorly understood. Because gut microbes commonly impact progression, metastasis, and immunotherapy responses in colorectal cancer (CRC), the roles of the esophageal microbiota in ESCC have gradually drawn attention. As reported previously, Fusobacterium nucleatum (Fn), the notable "culprit" of CRC, can also influence the prognosis of ESCC in clinical studies. However, thus far, the underlying mechanism is unclear. In this study, 73 Chinese ESCC samples were collected. In those clinical samples, the abundance of Fn was found to be higher in tumors than in adjacent normal tissues, and a high abundance of Fn was correlated with shorter survival. Furthermore, using in vitro experiments, we demonstrated that Fn can invade ESCC cells, enhancing their proliferation capacity. The mechanism study revealed that Fn can produce high levels of putrescine after invasion, which disturbs polyamine metabolism and promotes the malignant proliferation of ESCC cells. In conclusion, Fn infection was found in Chinese ESCC tumor tissue samples and may promote ESCC progression by disturbing the polyamine metabolism pathway. IMPORTANCE Nowadays, the complex and varied interactions between microbes and human body are known to be crucial for maintaining the health of the human body. However, knowledge concerning the influence of esophageal microbes on the progression of esophageal squamous cell carcinoma is limited. Here, in our study, we confirmed that F. nucleatum can invade ESCC cells and consequently promote their proliferation, suggesting that esophageal microbes likely influence the progression of ESCC in clinical settings. Because the esophagus connects the oral cavity and stomach, acting as a canal for transporting foods, its special physical location makes it easily exposed to microorganisms. Thus, it is necessary to explore the interaction between esophageal microbes and ESCC.

Dataset Information

FOXM1 Promotes Malignant Proliferation of Esophageal Squamous Cell Carcinoma Through Transcriptional Activating CDC6.

Publications

FOXM1 Promotes Malignant Proliferation of Esophageal Squamous Cell Carcinoma Through Transcriptional Activating CDC6.

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