肝细胞肝癌（HCC）是全球最常见且具有挑战性的癌症之一。N6-甲基腺苷（m6A）修饰和长非编码RNA（lncRNA）在HCC的进展中起着关键作用。然而，关于HCC中m6A甲基化lncRNA的全基因组筛选和功能注释的报道很少。通过RT-qPCR、公共数据集平台确定m6A甲基转移酶METTL3的表达水平及其与HCC预后的关联。随后，采用RNA-seq、Pearson相关分析、MeRIP-qPCR、RNA半衰期测定、基因位点定向突变、RIP分析和RT-qPCR分析来确定HCC中METTL3的下游靶点。然后，通过Kaplan-Meier曲线、RT-qPCR、体外功能实验和体内肿瘤发生和肺转移模型来确定lncRNA葡萄糖酰胺酶β假基因1（GBAP1）在HCC中的表达水平和作用。接下来，通过GO生物过程、KEGG通路富集、荧光素酶报告基因分析、RIP分析和救治实验等方法探究GBAP1的下游靶点和通路。结果显示，METTL3在HCC中上调表达，与HCC预后密切相关。METTL3通过作为GBAP1的m6A写入者诱导GBAP1的表达，而IGF2BP2则作为其m6A阅读蛋白。临床上，GBAP1表达与肿瘤大小、静脉浸润、TNM分期和HCC预后显著相关。功能上，GBAP1在体外和体内均促进了HCC的转移和生长。此外，GBAP1作为miR-22-3p的分子海绵，增加了骨形态发生蛋白受体1A（BMPR1A）的表达，进而激活了HCC细胞中的BMP/SMAD通路。我们的发现表明，METTL3诱导的GBAP1通过GBAP1/miR-22-3p/BMPR1A/SMAD轴促进了HCC细胞的迁移、侵袭和增殖。GBAP1可能是HCC的潜在预后指标和治疗靶点。© 2023. BioMed Central Ltd., part of Springer Nature.

Hepatocellular carcinoma (HCC) is one of the most common and challenging cancers in the world. N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play critical roles in the progression of HCC. However, there are few reports on genome-wide screening and functional annotations of m6A-methylated lncRNAs in HCC.The expression levels of m6A methyltransferase METTL3 and the association with the prognosis in HCC were determined by RT-qPCR, public dataset platforms. Then, RNA-seq, Pearson correlation analysis, MeRIP-qPCR, RNA half-life assay, gene site-directed mutation, RIP assay and RT-qPCR analysis were employed to determine the downstream target of METTL3 in HCC. Subsequently, the expression levels and roles of lncRNA glucosylceramidase beta pseudogene 1 (GBAP1) in HCC were determined by Kaplan-meier curves, RT-qPCR, in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. Then, the downstream target and pathway of GBAP1 were explored by GO biological process, KEGG pathway enrichment, luciferase reporter assay, RIP assay and rescue experiments and so on.METTL3 was upregulated in HCC and closely related to HCC prognosis. And METTL3 induced GBAP1 expression by acting as the m6A writer of GBAP1 and IGF2BP2 worked as its m6A reader. Clinically, GBAP1 expression was significantly associated with tumor size, venous infiltration, TNM stage and prognosis of HCC, Functionally, GBAP1 promoted HCC metastasis and growth both in vitro and in vivo. Furthermore, GBAP1 acted as the molecular sponge for miR-22-3p to increase the expression of bone morphogenetic protein receptor type 1A (BMPR1A), which then activated BMP/SMAD pathway in HCC cells.Our findings demonstrated that METTL3-induced GBAP1 promoted migration, invasion and proliferation of HCC cells via GBAP1/miR-22-3p/BMPR1A/SMAD axis. GBAP1 could be a potential prognosis indicator and therapeutic target for HCC.© 2023. BioMed Central Ltd., part of Springer Nature.