Dataset Information

Analysis and identification of m⁶A RNA methylation regulators in metastatic osteosarcoma.

ABSTRACT: Osteosarcoma (OS) is characterized by rapid growth and early metastasis. However, its mechanism remains unclear. N⁶-methyladenosine (m⁶A) modification and its regulatory factors play essential roles in most cancers, including OS. In this study, we screened out 21 m⁶A modifiers using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, followed by the identification of the critical m⁶A methylation modifiers. The results revealed that the expression levels of three m⁶A methylation regulators, namely RBM15, METTL3, and LRPPRC, were associated with the low survival rate of patients with OS. We further studied the independent prognostic factors by performing univariate and multivariate Cox analyses and found that metastasis was an independent prognostic factor for patients with OS. Furthermore, we found for the first time that RBM15 was specific for metastatic OS rather than non-metastatic OS. Moreover, the significant overexpression of RBM15 was validated in metastatic OS cell lines and in actual human clinical specimens. We also revealed that RBM15 promoted the invasion, migration, and metastasis of OS cells through loss-functional and gain-functional experiments and an animal metastatic model. In conclusion, RBM15 has a high correlation with OS metastasis formation and the decreased survival rate of patients with OS, and this may serve as a useful biomarker for predicting metastasis and prognosis of patients with OS.

SUBMITTER: Huang H

PROVIDER: S-EPMC8738956 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Analysis and identification of m6A RNA methylation regulators in metastatic osteosarcoma.

Huang Hanji H Cui Xiaofei X Qin Xiong X Li Kanglu K Yan Guohua G Lu Dejie D Zheng Mingjun M Hu Ziwei Z Lei Danqing D Lan Nihan N Zheng Li L Yuan Zhenchao Z Zhu Bo B Zhao Jinmin J

Molecular therapy. Nucleic acids 20211211

Osteosarcoma (OS) is characterized by rapid growth and early metastasis. However, its mechanism remains unclear. N6-methyladenosine (m6A) modification and its regulatory factors play essential roles in most cancers, including OS. In this study, we screened out 21 m6A modifiers using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, followed by the identification of the critical m6A methylation modifiers. The re ...[more]

PMID: 35036067

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Project description:RNA methylation accounts for over 60% of all RNA modifications, and N6-methyladenosine (m6A) is the most common modification on mRNA and lncRNA of human beings. It has been found that m6A modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The m6A modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of m6A RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 m6A RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of p < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed m6A RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of m6A RNA methylation regulators in prostate cancer and determined a m6A gene expression classifier that well predicted the prognosis of prostate cancer.

Dataset Information

Analysis and identification of m⁶A RNA methylation regulators in metastatic osteosarcoma.

Publications

Analysis and identification of m<sup>6</sup>A RNA methylation regulators in metastatic osteosarcoma.

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