LncRNA FOXP4-AS1 Promotes Progression of Ewing Sarcoma and Is Associated With Immune Infiltrates

Xiong, Jiachao; Wu, Liang; Wu, Chunyang; Liu, Zhiming; Deng, Wenqiang; Ma, Shengbiao; Zhou, Zhenhai; Yu, Honggui; Cao, Kai

doi:10.3389/fonc.2021.718876

Cited by 11 publications

(9 citation statements)

References 57 publications

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“…Furthermore, lncRNA FOXP4-AS1 was downregulated in three thyroid carcinoma cell lines compared to normal thyroid cells ( Figure 1I ). Besides, the fluorescence in situ hybridization (FISH) results showed that FOXP4-AS1 distributes predominantly in the PTC cell cytoplasm ( Figure 1J ), which was consistent with Xiong et al.’s report ( 22 ).…”

Section: Resultssupporting

confidence: 91%

“…It was researched that FOXP4-AS1 can not only modulate the epigenetic modification of the genome by recruiting epigenetic modification proteins in the nucleus but also affect the regulation of miRNAs on target genes by acting as a molecular sponge for miRNAs in the cytoplasm, in tumor studies. We went further to detect its subcellular localization and found that it localized at the cytoplasm of thyroid cells consistent with a previous report ( 22 ). Therefore, we speculate that FOXP4-AS1 functions as a tumor suppressor in PTC through two possible ways: acting as a miRNA sponge or regulating the stability of its binding proteins.…”

Section: Discussionsupporting

confidence: 89%

“…lncRNA FOXP4-AS1 is a new cancer-related biomarker that has emerged in recent years, whose roles are diverse in different cancers. It has been reported in several studies with solid proof that FOXP4-AS1 is overexpressed in hepatocellular carcinoma ( 17 ), esophageal squamous cell carcinoma ( 18 ), prostate cancer ( 19 ), nasopharyngeal carcinoma ( 20 , 21 ), Ewing sarcoma (ES) ( 22 ), mantle cell lymphoma (MCL) ( 23 ), and osteosarcoma ( 24 ), where it promoted cancer progression and played an oncogenic role, and its upregulation usually predicts poor prognosis of these cancers. More importantly, there were reports that indicated that the upregulation of FOXP4-AS1 showed longer overall survival in ovarian cancer ( 25 , 26 ), suggesting that it could be an efficacious prognostic biomarker.…”

Section: Introductionmentioning

confidence: 99%

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FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway

et al. 2022

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Papillary thyroid carcinoma, also known as PTC, is one of the commonest malignancies in the endocrine system. Long non-coding RNAs (lncRNAs) in PTC could maintain proliferative signaling, induce therapeutic resistance, activate invasion and migration, and sustain stem cell-like characteristics. In this paper, results showed that lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) is downregulated in PTC tissues and cell lines. Patients in TCGA cohort with a higher FOXP4-AS1 expression showed a higher disease-free interval (DFI) rate, and the expression of FOXP4-AS1 is shown to be linked to the clinical stage, T stage, N stage, and extraglandular invasion condition of the TC patients. FOXP4-AS1 is localized in the cell cytoplasmic domain of PTC cells. Functionally, upregulated FOXP4-AS1 inhibited PTC cell proliferation, apoptosis, and migration, whereas it downregulated FOXP4-AS1-promoted progression of PTC. In vivo assay also confirmed the tumor inhibitory effect of FOXP4-AS1 in PTC growth. Mechanism analysis indicated that FOXP4-AS1 can play its functions by regulating the AKT signaling pathway, and AKT inhibitor treatment could attenuate the impact of FOXP4-AS1 on PTC progression. Furthermore, FOXP4-AS1 also negatively regulates the expression of its host gene FOXP4. Collectively, we showed that FOXP4-AS1 inhibited PTC progression although AKT signaling and FOXP4-AS1 plays a tumor-suppressor role in PTC tumorigenesis.

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Section: Resultssupporting

confidence: 91%

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway

et al. 2022

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“…lncRNAs are RNA molecules with transcripts that are longer than 200 nucleotides, which were initially thought to be by-products of RNA polymerase II transcription [4]. lncRNAs are important regulatory molecules in the process of tumorigenesis [5][6][7]. In addition, lncRNAs are also associated with tumor invasion, in ltration, metastasis, and prognosis [8].…”

Section: Introductionmentioning

confidence: 99%

A Newly Established Cuproptosis-Associated Long Non-Coding RNA Signature for Predicting Prognosis and Indicating Immune Microenvironment Features in Soft Tissue Sarcoma

Han

Liu

et al. 2022

Journal of Oncology

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Cuproptosis, a new type of programmed cell death, is involved in the development and progression of malignancies. The study of cuproptosis-associated long non-coding RNAs (lncRNAs) in soft tissue sarcomas (STSs) is however limited. There is also uncertainty regarding the prognostic accuracy of cuproptosis-associated lncRNAs in STSs and their relationship to the tumor immune microenvironment. The aim of this study was to determine the prognostic significance of cuprotosis-associated lncRNAs in STSs and their relationship to the tumor immune microenvironment. Transcriptomic and clinical data from patients with STSs were obtained through The Cancer Genome Atlas (TCGA). Overall, 259 patients were randomly allocated to a training group or a testing group. In the training group, a cuproptosis-associated lncRNA signature was constructed, and the signature was verified in the testing group. On the basis of risk scores and clinical features, we later developed a hybrid nomogram. We also performed functional and tumor immune microenvironment analysis based on the cuproptosis-associated lncRNA signature. A signature of 5 cuproptosis-associated lncRNAs was created. Based on this signature, we categorized STS patients into high-risk and low-risk groups. The study showed that patients at high risk had a worse prognosis than those at low risk. A nomogram was then constructed combining clinical characteristics with the risk scores, and it was shown to have credible predictive power. Functional enrichment and tumor immune microenvironmental analyses showed that high-risk STSs tend to be immunologically sensitive tumors. In our study, we found a cuproptosis-associated lncRNAs signature, which serves as an independent prognostic indicator. Cuproptosis-associated lncRNAs may play a role in the tumor immune microenvironment, which might be a therapeutic target for patients with STSs.

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“…In the elimination and equilibrium phases, sarcoma-secreted exosomes containing lncRNA FOXP4-AS1 could recruit innate immune cells to TME, including Tregs, activated NK cells, and M1 macrophages [ 54 ]. The infiltrating immune cells had either tumor-promoting or tumor-suppressive effects.…”

Section: The Roles Of Exosomes In Sarcoma Tmementioning

confidence: 99%

Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications

Yang

et al. 2022

J Nanobiotechnol

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The current diagnosis and treatment of sarcoma continue to show limited timeliness and efficacy. In order to enable the early detection and management of sarcoma, increasing attentions have been given to the tumor microenvironment (TME). TME is a dynamic network composed of multiple cells, extracellular matrix, vasculature, and exosomes. Exosomes are nano-sized extracellular vesicles derived from various cells in the TME. The major function of exosomes is to promote cancer progress and metastasis through mediating bidirectional cellular communications between sarcoma cells and TME cells. Due to the content specificity, cell tropism, and bioavailability, exosomes have been regarded as promising diagnostic and prognostic biomarkers, and therapeutic vehicles for sarcoma. This review summarizes recent studies on the roles of exosomes in TME of sarcoma, and explores the emerging clinical applications.

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LncRNA FOXP4-AS1 Promotes Progression of Ewing Sarcoma and Is Associated With Immune Infiltrates

Cited by 11 publications

References 57 publications

FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway

FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway

A Newly Established Cuproptosis-Associated Long Non-Coding RNA Signature for Predicting Prognosis and Indicating Immune Microenvironment Features in Soft Tissue Sarcoma

Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications

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