Background: Osteosarcoma is the most common primary malignant bone tumor in children and young adults. RNA N-methyladenosine (mA) is the most abundant internal modification in mammalian mRNA, which is involved in tumorigenesis and tumor progression. It has been reported that methyltransferase-like 3 (METTL3), the first reported m6A "writer", plays critical roles in cancer progression. However, its role and molecular mechanism in osteosarcoma is poor studied. In this study, we aimed to investigate the functional role and underlying mechanism of METTL3 in the progression of osteosarcoma.
Methods: We detected the mRNA expression of METTL3 in osteosarcoma cell lines, and immunofluorescence assay was performed to observe the location of METTL3. Cell lines with METTL3 gene overexpression or knockdown were established by pcDNA3.1-METTL3 or siRNA interferences in order to determine the function of METTL3 in osteosarcoma in vitro. Transcriptomic RNA sequencing (RNA-seq) were used to screen the target genes of METTL3 in osteosarcoma.
Results: We found that METTL3 localized in cytoplasm and nucleus of osteosarcoma cells. Silencing METTL3 in SAOS-2 and MG63 cells significantly inhibited the mA methylation level, proliferation, migration, and invasion abilities, as well as promoted cell apoptosis. However, up-regulation of METTL3 had no significant effect on the biological behaviors of U2OS cells. Further mechanism analysis suggested that METTL3 knockdown inhibited the expression of ATPase family AAA domain containing 2 (ATAD2). Moreover, ATAD2 knockdown inhibited the proliferation and invasion of SAOS-2 and MG63 cells, while its overexpression showed a significant increase in cell proliferation and invasion. Furthermore, METTL3 knockdown abrogated the promoting effects of ATAD2 overexpression on osteosarcoma cells proliferation and invasion.
Conclusion: Overall, our study revealed that METTL3 functions as an oncogene in the growth and invasion of osteosarcoma by regulating ATAD2, suggesting a potential therapeutic target for osteosarcoma treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biopha.2020.109964 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Suppression of METTL3 expression attenuated matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the extracellular matrix in pelvic organ prolapse.
Chin Med J (Engl)
January 2025
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing 100730, China.
Background: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP.
Methods: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts.
and Regulate Heat Stress Response in Hu Sheep Through Lipid Metabolism via m6A Modification.
Animals (Basel)
January 2025
Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.
In an established hepatocyte lipid deposition heat stress model, the expression levels of and were significantly upregulated ( < 0.05), indicating that and play important roles in the process of lipid deposition heat stress in hepatocytes. Transcriptome and metabolome analyses showed that lipid deposition heat stress had significant effects on the linoleic acid, linolenic acid, glycerophospholipid, and arachidonic acid metabolic pathways in hepatocytes.
View Article and Find Full Text PDFMETTL3-dependent DLG2 inhibits the malignant progression of cervical cancer by inactivating the Hippo/YAP signaling.
Hereditas
January 2025
Department of Dermatology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou, 646000, China.
Background: Discs large homolog 2 (DLG2) has been implicated in cancer development, yet its role in cervical cancer remains unclear. This study aims to explore the regulatory mechanism of DLG2 in cervical cancer and its clinical implications.
Methods: Quantitative reverse transcription polymerase chain reaction and western blotting assays were employed to detect RNA and protein expression, respectively.
METTL3: a multifunctional regulator in diseases.
Mol Cell Biochem
January 2025
Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
N6-methyladenosine (mA) methylation is the most prevalent and abundant internal modification of mRNAs and is catalyzed by the methyltransferase complex. Methyltransferase-like 3 (METTL3), the best-known mA methyltransferase, has been confirmed to function as a multifunctional regulator in the reversible epitranscriptome modulation of mA modification according to follow-up studies. Accumulating evidence in recent years has shown that METTL3 can regulate a variety of functional genes, that aberrant expression of METTL3 is usually associated with many pathological conditions, and that its expression regulatory mechanism is related mainly to its methyltransferase activity or mRNA posttranslational modification.
View Article and Find Full Text PDFm6A Demethylase -Mediated Upregulation of Induces Neuronal Ferroptosis via the Axis in the MPP/MPTP-Induced Parkinson's Disease Model.
ACS Chem Neurosci
January 2025
Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, P.R. China.
: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the involvement of ferroptosis in its pathological mechanism. In this study, the effects and mechanism of BRCA1-associated protein 1 (BAP1) on neuronal ferroptosis in PD were evaluated. : A PD mouse model was constructed by injecting mice with MPTP.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!