METTL16 promotes cell proliferation by up‐regulating cyclin D1 expression in gastric cancer

Wang, Xiao‑Kun; Zhang, Ya‐Wei; Wang, Chunming; Li, Bo; Zhang, Tianzhi; Zhou, Wenjie; Cheng, Linlin; Huo, Mingyu; Zhang, Changhua; He, Yulong

doi:10.1111/jcmm.16664

Cited by 68 publications

(55 citation statements)

References 34 publications

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“…The BCA protein assay kit (KeyGEN BioTECH, cat#KGP903) was used to valuate the protein concentration. Western blot was performed as previously described ( Wang et al, 2021 ). The following antibodies were used: anti-ITGAL (Abclonal, cat#A1644) and anti‐GAPDH (Proteintech, cat#60004‐1‐Ig).…”

Section: Methodsmentioning

confidence: 99%

ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer

Wang

Yuan

et al. 2022

Front. Cell Dev. Biol.

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Integrin alpha L (ITGAL) is a member of the integrin family in which the abnormal expression is linked with carcinogenesis and immune regulation. However, the relation between ITGAL and the prognosis of gastric cancer (GC) and tumor-infiltrating lymphocytes (TILs) are not well understood. The differential expressions of ITGAL in human tumors and the clinical prognosis in GC were systematically analyzed via multiple databases including Gene Expression Profiling Interaction Analysis (GEPIA), UALCAN, Tumor Immune Estimation Resource (TIMER), and Kaplan–Meier (KM) plotter. TIMER, GEPIA, and TISIDB databases were used to comprehensively investigate the correlation between ITGAL and tumor infiltration immune cells. Also, further results were investigated by immunohistochemistry, qRT-PCR, and Western blot. We found that ITGAL expression in GC samples was considerably increased than in peritumor samples. Sample type, subgroup, cancer stage, lymphatic node stage, and worse survival were strongly related to high ITGAL expression. Moreover, upregulated ITGAL expression was strongly connected with immunomodulators, chemokines, and infiltrating levels of CD8+, CD4+ T cell, B cell, monocyte, neutrophil, macrophage, T-cell regulatory, NK cell, and myeloid dendritic cell in stomach adenocarcinoma (STAD). Specifically, immunohistochemistry and bioinformatic analysis showed that ITGAL expression was shown to have strong relationships with various immunological marker sets including PD1 (T-cell exhaustion marker). In conclusion, ITGAL is a prognostic biomarker for GC patients. It might regulate tumor immune microenvironment leading to poor prognosis. Furthermore, studies are essential to explore therapeutic targeting ITGAL.

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Section: Methodsmentioning

confidence: 99%

ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer

Wang

Yuan

et al. 2022

Front. Cell Dev. Biol.

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“…METTL16 is a recently identified m 6 A methyltransferase, which has important roles in embryonic development [ 21 ]. Although the oncogenic roles of METTL16 in gastric cancer has been reported [ 22 ], the role, expression, and clinical relevance of METTL16 in other cancers, including HCC, are still unclear. As an m 6 A writer, METTL16 was reported to directly deposit m 6 A in only MAT2A mRNA and U6 small nuclear RNA (snRNA) [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m6A-dependent manner

Dai¹,

Liu²,

Li³

et al. 2022

Cell Mol Biol Lett

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Background The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N6-methyladenosine (m6A) plays key roles in HCC. The aim of this study was to investigate the expression, roles, and mechanisms of action of the RNA methyltransferase methyltransferase-like protein 16 (METTL16) in HCC. Methods The expression of METTL16 and RAB11B-AS1 was determined by RT-qPCR. The regulation of RAB11B-AS1 by METTL16 was investigated by RNA immunoprecipitation (RIP), methylated RIP (MeRIP), and RNA stability assays. In vitro and in vivo gain- and loss-of-function assays were performed to investigate the roles of METTL16 and RAB11B-AS1. Results METTL16 was upregulated in HCC, and its increased expression was correlated with poor prognosis of HCC patients. METTL16 promoted HCC cellular proliferation, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumoral growth in vivo. METTL16 directly bound long noncoding RNA (lncRNA) RAB11B-AS1, induced m6A modification of RAB11B-AS1, and decreased the stability of RAB11B-AS1 transcript, leading to the downregulation of RAB11B-AS1. Conversely to METTL16, RAB11B-AS1 is downregulated in HCC, and its decreased expression was correlated with poor prognosis of patients with HCC. Furthermore, the expression of RAB11B-AS1 was negatively correlated with METTL16 in HCC tissues. RAB11B-AS1 repressed HCC cellular proliferation, migration, and invasion, promoted HCC cellular apoptosis, and inhibited HCC tumoral growth in vivo. Functional rescue assays revealed that overexpression of RAB11B-AS1 reversed the oncogenic roles of METTL16 in HCC. Conclusions This study identified the METTL16/RAB11B-AS1 regulatory axis in HCC, which represented novel targets for HCC prognosis and treatment.

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“…The "writer" gene KIAA1429 displayed a common trend in ALKBH5 (an "eraser" gene) expression in IBD. Previous studies find that m 6 A writers that increase the RNA m 6 A level are oncogenes (Lan et al, 2019;Qian et al, 2019;Wang X. K. et al, 2021), and FTO and ALKBH5 that decrease the RNA m 6 A level are also oncogenes (Shen et al, 2020;Su et al, 2020). The targets of "erasers" and "writers" that are reported in different studies are different, suggesting different mechanisms and other regulatory factors exist in disease development other than the "writer" and "eraser."…”

Section: Discussionmentioning

confidence: 96%

m6A Modification Mediates Mucosal Immune Microenvironment and Therapeutic Response in Inflammatory Bowel Disease

Chen

Lei

2021

Front. Cell Dev. Biol.

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Accumulating evidence links m6A modification with immune infiltration. However, the correlation and mechanism by which m6A modification promotes intestinal immune infiltration in inflammatory bowel disease (IBD) is unknown. Here, genomic information from IBD tissues was integrated to evaluate disease-related m6A modification, and the correlation between the m6A modification pattern and the immune microenvironment in the intestinal mucosa was explored. Next, we identified hub genes from the key modules of the m6Acluster and analyzed the correlation among the hub genes, immune infiltration, and therapy. We found that IGF2BP1 and IGF2BP2 expression was decreased in Crohn’s disease (CD) tissues and that IGF2BP2 was decreased in ulcerative colitis (UC) tissues compared with normal tissues (P < 0.05). m6Acluster2, containing higher expressions of IL15, IL16, and IL18, was enriched in M0 macrophage, M1 macrophage, native B cells, memory B cells, and m6Acluster1 with high expression of IL8 and was enriched in resting dendritic and plasma cells (P < 0.05). Furthermore, we reveal that expression of m6A phenotype-related hub genes (i.e., NUP37, SNRPG, H2AFZ) was increased with a high abundance of M1 macrophages, M0 macrophages, and naive B cells in IBD (P < 0.01). Immune checkpoint expression in the genecluster1 with higher expression of hub genes was increased. The anti-TNF therapeutic response of patients in genecluster1 was more significant, and the therapeutic effect of CD was better than that of UC. These findings indicate that m6A modification may affect immune infiltration and therapeutic response in IBD. Assessing the expression of m6A phenotype-related hub genes might guide the choice of IBD drugs and improve the prediction of therapeutic response to anti-TNF therapy.

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METTL16 promotes cell proliferation by up‐regulating cyclin D1 expression in gastric cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 68 publications

References 34 publications

ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer

ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer

METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m6A-dependent manner

m6A Modification Mediates Mucosal Immune Microenvironment and Therapeutic Response in Inflammatory Bowel Disease

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