标题：Silencing METTL3 inhibits the proliferation and invasion of osteosarcoma by regulating ATAD2
作者：Zhou, Lei; Yang, Changsheng; Zhang, Ning; Zhang, Xin; Zhao, Tingbao; Yu, Jinming
作者机构：[Zhou, Lei; Yang, Changsheng; Zhang, Xin; Zhao, Tingbao] Shandong Univ, Shandong Canc Hosp & Inst, Dept Orthoped Oncol Surg, Jinan 250117, Peoples R C 更多
通讯作者地址：Yu, JM (corresponding author), Shandong Univ, Shandong Canc Hosp & Inst, Dept Radiat Oncol, 440 Jiyan Rd, Jinan 250117, Peoples R China.
来源：BIOMEDICINE & PHARMACOTHERAPY
关键词：METTL3; Osteosarcoma; m(6)A methylation; Proliferation; Invasion; ATAD2
摘要：Background: Osteosarcoma is the most common primary malignant bone tumor in children and young adults. RNA N-6-methyladenosine (m(6)A) 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 m(6)A 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.