Ask about this productRelated genes to: KIAA1627 antibody
- Gene:
- METTL14 NIH gene
- Name:
- methyltransferase like 14
- Previous symbol:
- -
- Synonyms:
- KIAA1627
- Chromosome:
- 4q26
- Locus Type:
- gene with protein product
- Date approved:
- 2009-02-24
- Date modifiied:
- 2017-07-11
Related products to: KIAA1627 antibody
Related articles to: KIAA1627 antibody
- - Source: PubMed
Publication date: 2026/04/27
Wu Hui-HuiLi Yue-YanMeng Fan-LiangDu Jia-MinZheng YanSong Chun-HongLi Li-MingLi YingSu Guo-Hai - Restoring CD8⁺T cell infiltration and potentiating anti-tumor immune responses in the tumor microenvironment (TME) is critical for developing effective immunotherapies against triple-negative breast cancer(TNBC), while the regulatory role of N⁶-methyladenosine (m⁶A)-modified circular RNAs (circRNAs) in TNBC immune escape remains largely unelucidated. Whole-transcriptome microarray analysis combined with bioinformatics mining was conducted on TNBC tissues to screen circRNAs associated with immune evasion. RNA immunoprecipitation (RIP), RNA pulldown, and methylated RNA immunoprecipitation (MeRIP) assays were performed to verify the m⁶A modification of circFOXA1 and its interaction with gasdermin C (GSDMC). In vitro T cell-mediated tumor cytotoxicity assays and in vivo xenograft models in C57BL/6 mice were used to investigate the functional roles of the circFOXA1/GSDMC axis in TNBC anti-tumor immunity. Luciferase reporter and actinomycin D assays were further applied to clarify the regulatory mechanism of GSDMC on OTUB1 and programmed cell death-ligand 1 (PD-L1) expression. CircFOXA1 was identified as an m⁶A-modified circRNA with high stability and upregulation in TNBC, and its expression was significantly negatively correlated with CD8⁺T cell infiltration in TNBC tissues. Functionally, circFOXA1 induced immunosuppression in a CD8⁺T cell-dependent manner both in vitro and in vivo. Mechanistically, the m⁶A writer METTL14 mediated the m⁶A modification of circFOXA1, and the m⁶A reader YTHDF2 promoted circFOXA1 circularization. CircFOXA1 impaired immune cell-dependent tumor killing by upregulating GSDMC expression, which further enhanced OTUB1 mRNA stability at the post-transcriptional level. OTUB1-mediated deubiquitination subsequently stabilized PD-L1 protein, ultimately inhibiting CD8⁺T cell infiltration and driving TNBC immune escape. This study identifies a novel regulatory axis of m⁶A-modified circFOXA1/GSDMC/OTUB1/PD-L1 in mediating TNBC immune escape, where GSDMC enhances PD-L1 protein stability via OTUB1-dependent deubiquitination. These findings reveal a new molecular mechanism underlying TNBC immune evasion and identify circFOXA1 as a potential therapeutic target to improve the efficacy of anti-PD-1/PD-L1 immunotherapy in TNBC. - Source: PubMed
Publication date: 2026/04/22
Shen HonghongLi BoyuWen XiaoqianZhao ChangqingWang Chen - Post-transcriptional RNA modifications, such as N6-methyladenosine (m6A) methylation and adenosine to inosine (A-to-I) editing, are critical regulators of hematopoietic stem cell (HSC) self-renewal and differentiation, yet their precise contributions to malignant transformation are not fully elucidated. In this study, we uncovered the epitranscriptomic landscape caused by knockdown of genes from the methyltransferase (METTL)-family in hematopoietic stem and progenitor cells (HSPCs). We identified both converging and distinct effects of METTL3 and METTL14, known members of the m6A writer complex, as well as orphan gene METTL13. Amongst METTL-family members, only METTL13 transcription was increased following adenosine deaminase acting on RNA 1 (ADAR1) overexpression in HSPCs. This transcriptional pattern suggests that METTL13 may participate in biological programs that partially overlap with those controlled by the m6A writer complex and ADAR1, although any mechanistic relationship remains undefined. Knockdown of METTL13 altered the expression of multiple genes involved in oncogenic development in HSPCs. Furthermore, METTL13 expression was associated with a high-risk profile in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and functional studies confirmed that METTL13 is required for T-ALL cell proliferation and survival both in vitro and in vivo. Collectively, our results identify METTL13 as a previously unrecognized regulator of leukemic transformation, independent of any presumed mechanistic interaction between RNA editing and m6A pathways. - Source: PubMed
Publication date: 2026/04/25
Enlund SabinaLim Chae-EunHoang IsabellaJoshi SonaliRivera MariaPepich AdenaRamilo Amor AmandaShort JacobThomsson CeciliaSinha IndranilFard Shahrzad ShiraziNilsson AnnaHermanson OlaJiang QingfeiHolm Frida - Hepatocellular carcinoma (HCC) has a dismal prognosis with limited therapeutic options, and drug repurposing is a promising anti-HCC strategy. Pyrimethamine (Pyr), an FDA-approved antifolate drug with potential antitumor activity, its molecular mechanism in HCC remains elusive. In this study, in vitro experiments (MTT, colony formation, flow cytometry) confirmed that Pyr dose-dependently inhibited Hep3B and Huh7 cell proliferation, induced DNA damage and G0/G1 cell cycle arrest, and downregulated CCND1 expression. Mechanistically, Pyr upregulated METTL14 to enhance global m6A modification, and METTL14 directly mediated the m6A modification of CCND1 mRNA; the modified CCND1 was specifically recognized by YTHDF2, leading to its mRNA degradation. Bioinformatic and clinical sample analyses verified that METTL14 was downregulated in HCC tissues and acted as a tumor suppressor in vitro. In HCC patient-derived xenograft (PDX) models, Pyr significantly suppressed tumor growth, upregulated METTL14 and YTHDF2 expression, downregulated CCND1, and exhibited no obvious organ toxicity. This study reveals that Pyr exerts anti-HCC activity by activating the METTL14/YTHDF2 axis to induce m6A-dependent CCND1 mRNA degradation and subsequent G0/G1 arrest, uncovers a novel epitranscriptomic mechanism of Pyr, and supports its repurposing as a potential therapeutic agent for HCC. - Source: PubMed
Publication date: 2026/04/17
Han XiaoWang KailongLiu CaiyanYin ShuangshuangShao YingyingZhang JinWang DongPan GuixiangYu Haiyang - Non-small cell lung cancer (NSCLC) accounts for the highest proportion of lung cancers. METTL14 is a m6A methyltransferase affects the development of NSCLC. Lactylation can induced by glycolysis production lactate, but whether it modulates NSCLC through m6A methylation remains unclear. We aimed to determine whether METTL14 mediates NSCLC through glycolysis. - Source: PubMed
Publication date: 2026/04/23
Wang QibinLiu Guangjun