Dataset Information

NSUN2 Promotes Tumor Progression and Regulates Immune Infiltration in Nasopharyngeal Carcinoma.

ABSTRACT: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in the head and neck with a complex etiology, such as environmental factors, genetic factors, and Epstein-Barr virus infection. The NOP2/Sun domain family, member 2 (NSUN2) is a methyltransferase of m5C methylation modification that has been reported to be involved in the occurrence and progression of various tumors, but its role in NPC remains unclear. In this study, we found that NSUN2 was upregulated in NPC and predicted a poor prognosis for NPC patients in both GEO datasets and our tissue microarrays containing 125 NPC tissues. Next, we demonstrated that NSUN2 promoted the proliferation, migration, and invasion of NPC cells in vitro. Additionally, the differential expression genes between NSUN2-high and low expression patients were mainly enriched in multi-immune cell activation and proliferation. Furthermore, NSUN2 negatively regulates immune cell infiltration in the tumor microenvironment (TME) of NPC, which indicates that the NSUN2 level may be negatively correlated with the sensitivity of immunotherapy and chemotherapy. In conclusion, our findings highlight that NSUN2 might act as an important oncogene involved in NPC progression and serve as a potential biomarker to predict poor prognosis and drug sensitivity of NPC patients.

SUBMITTER: Tong X

PROVIDER: S-EPMC9099203 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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NSUN2 Promotes Tumor Progression and Regulates Immune Infiltration in Nasopharyngeal Carcinoma.

Tong Xinya X Xiang Yilan Y Hu Yuanbo Y Hu Yingying Y Li He H Wang Huilin H Zhao Kong-Nan KN Xue Xiangyang X Zhu Shanli S

Frontiers in oncology 20220429

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in the head and neck with a complex etiology, such as environmental factors, genetic factors, and Epstein-Barr virus infection. The NOP2/Sun domain family, member 2 (NSUN2) is a methyltransferase of m5C methylation modification that has been reported to be involved in the occurrence and progression of various tumors, but its role in NPC remains unclear. In this study, we found that NSUN2 was upregulated in NPC and predicted a ...[more]

PMID: 35574373

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Project description:Objective: The transcription factor forkhead box protein O1 (FOXO1) is critical for regulating cytokine and chemokine secretion. However, its function in the tumor microenvironment (TME) remains largely unexplored. In this study, we characterized the prognostic value of FOXO1 and the interaction between tumor-derived FOXO1 and M2 macrophages in esophageal squamous cell carcinoma (ESCC). Methods: FOXO1 expression and macrophage infiltration in clinical samples and mouse models were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry staining. Western blotting, qRT-PCR, and enzyme-linked immunosorbent assay were used to evaluate chemokine ligand 20 (CCL20) and colony stimulating factor 1 (CSF-1) expression in FOXO1(+) and FOXO1(-) tumor cells. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and RNA sequencing. Transcriptional activity was measured using chromatin immunoprecipitation (ChIP)-qPCR. Tumor viability was investigated using XTT proliferation and foci formation assays. Results: FOXO1 upregulation in tumor tissues was found to drive the polarization of M0 macrophages and infiltration of M2 macrophages into the TME, resulting in worse prognosis in ESCC patients. CSF-1, a vital factor inducing M0-to-M2 polarization, was upregulated via a FOXO1-mediated mechanism. RNA sequencing results corroborated that the FOXO1-induced macrophages exhibited similar molecular signatures to the IL4-stimulated M2 macrophages. The transwell assays showed that FOXO1 promoted the migration of M2 macrophages via CCL20 secretion, which could be inhibited using an anti-CCL20 antibody. FOXO1(+) tumor-induced M2 macrophages promoted tumor proliferation via the FAK-PI3K-AKT pathway and the PI3K inhibitor could effectively impede the oncogenical process. Conclusions: FOXO1 facilitated M0-to-M2 polarization and the recruitment of M2 macrophages in the TME via the transcriptional modulation of CCL20 and CSF-1. Our data deciphered the FOXO1-dependent mechanism in M2 macrophage infiltration in the TME of ESCC, which has implications for the development of novel prognostic and therapeutic targets to optimize the current treatment against ESCC.

Dataset Information

NSUN2 Promotes Tumor Progression and Regulates Immune Infiltration in Nasopharyngeal Carcinoma.

Publications

NSUN2 Promotes Tumor Progression and Regulates Immune Infiltration in Nasopharyngeal Carcinoma.

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