Analysis of METTL3 and METTL14 in hepatocellular carcinoma

Liu, Xiangxiang; Qin, Jian; Gao, Tianyi; Li, Chenmeng; Chen, Xiaoxiang; Zeng, Ke; Xu, Mu; He, Bangshun; Pan, Bei; Xu, Xueni; Pan, Yuqin; Sun, Huiling; Xu, Tan; Wang, Shukui

doi:10.18632/aging.103959

Cited by 51 publications

(40 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In parallel, it was found that YTHDF2 suppress inflammation and angiogenesis in the tumor cell hypoxia environment (Hou et al, 2019). METTL3 enhances HCC cell growth ability (Liu et al, 2020;Yang et al, 2021). METTL14 suppresses the metastatic potential of HCC by modulating m6A-dependent tumor-suppressor primary miRNA processing (Ma et al, 2017;Shi et al, 2020).…”

Section: Discussionmentioning

confidence: 98%

m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

Wang

Zhou

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Background: Immunotherapy elicits durable responses in many tumors. Nevertheless, the positive response to immunotherapy always depends on the dynamic interactions between the tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of immunotherapy in hepatocellular carcinoma (HCC) has achieved limited success. The ectopic modification of N6-methyladenosine (m6A) is a common feature in multiple tumors. However, the relationship between m6A modification with HCC clinical features, prognosis, immune cell infiltration, and immunotherapy efficacy remains unclear.Materials and Methods: Here, we comprehensively evaluated m6A modification clusters based on 22 m6A regulators and systematically explored the relationship between m6A modification with tumor progression, prognosis, and immune cell infiltration characteristics. The m6Ascore was calculated by principal component analysis to quantify the m6A modifications of individual patients. Key regulators involved in immunoregulation in HCC were identified using immunohistochemistry and immunofluorescence.Results: Three distinct m6A modification clusters were identified. The m6A clusters were significantly associated with clinical features, prognosis, and immune cell infiltration. The three clusters were highly consistent with the three tumor immune phenotypes, i.e., immune-excluded, immune-inflamed, and immune-desert. Comprehensive bioinformatics analysis revealed that high m6Ascore was closely associated with tumor progression, poor prognosis, and immunotherapy non-response. m6A regulators were dysregulated in HCC tissues. Hence, they play a role as predictors of poor prognosis. Tissue microarray demonstrated that overexpressed YTHDF1 was associated with low CD3+ and CD8+ T cell infiltration in HCC.Conclusion: Our findings demonstrate that m6A modification patterns play a crucial role in the tumor immune microenvironment and the prognosis of HCC. High YTHDF1 expression is closely associated with low CD3+ and CD8+ T cell infiltration in HCC.

show abstract

Section: Discussionmentioning

confidence: 98%

m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

Wang

Zhou

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…31 METTL3 has been indicated to be upregulated in HCC 32. while METTL3 and METTL14 hold opposite regulatory roles in HCC. 33 In this study, it was perceived that the MEG3 gene was modified by m6A in HCC cells. At the same time, it was found that METTL3 can directly interact with MEG3 indicating that METTL3 is involved in the m6A modification of MEG3.…”

Section: Dovepressmentioning

confidence: 89%

m6A-Induced LncRNA MEG3 Suppresses the Proliferation, Migration and Invasion of Hepatocellular Carcinoma Cell Through miR-544b/BTG2 Signaling

Wu¹,

Pang²,

Li³

et al. 2021

OTT

View full text Add to dashboard Cite

Objective Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Long non-coding RNA plays an important role in the development of HCC. This study analyzed the impact of MEG3 on malignant behavior of HCC and explored its possible molecular mechanism. Methods Expression of MEG3 in HCC tissues and cell lines was measured by qRT-PCR. Transfection efficiency of MEG3 was verified by qRT-PCR. Cell proliferation, transwell migration, invasion and cell cloning assays were used to detect the effect of MEG3 on the proliferation, migration and invasion ability of HCC cells. The bioinformatics analysis was applied to predict the binding between miR-544b and MEG3 as well as BTG2. Luciferase reporter assay was performed to verify their interaction. Finally, the m6A modification of MEG3 by METTL3 was identified through RIP experiments. Results MEG3 was lowly expressed in HCC tissues and cells. Overexpression of MEG3 inhibits the proliferation, migration and invasion of HCC cells. MiR-544b can be sponged by MEG3, and overexpression of miR-544b reverses the anti-cancer effect of MEG3. We further confirmed that BTG2 gene is the target gene of miR-544b. Epigenetic studies have shown that METTL3-mediated N 6 -methyladenosine modification led to MEG3 downregulation. Conclusion In HCC, MEG3 and BTG2 are lowly expressed while miR-544b is highly expressed. MEG3 regulates the expression of BTG2 through miR-544b, thus affecting the malignant behavior of HCC. METTL3 regulates the m6A modification of MEG3 and its expression. This study clarified the role of MEG3/miR-544b/BTG2 axis in HCC and also provided new targets for HCC research.

show abstract

“…Certain studies have demonstrated that METTL3 serves a regulatory role in a variety of cancer types, such as breast, bladder and lung cancer, as well as hepatocellular carcinoma (31)(32)(33)(34)(35). For example, METTL3 can act as an oncogene in bladder tumorigenesis (36); however, METTL3 and METTL14 also serve as tumor suppressors in hepatocellular carcinoma (37,38). Certain studies have reported that METTL3 contributes to transforming growth factor-β-induced epithelial-mesenchymal transition of lung cancer cells (39).…”

Section: Discussionmentioning

confidence: 99%

METTL3‑mediated m6A modification of Bcl‑2 mRNA promotes non‑small cell lung cancer progression

et al. 2021

View full text Add to dashboard Cite

Methyltransferase-like 3 (METTL3) is an RNA methyltransferase that mediates modification of N6-methyladenosine (m6A), which serves as an oncogene in various types of cancer. The role of m6A modification in the onset and progression of cancer has attracted growing attention. However, the functional and regulatory mechanisms of METTL3 in non-small cell lung cancer (NSCLC) progression are still poorly understood. In the present study, METTL3 expression in NSCLC tissue was analyzed using the Gene Expression Profiling Interactive Analysis database. Western blotting and reverse transcription-quantitative PCR were performed to evaluate the expression of METTL3 in NSCLC tissue and cell lines. Here, knockdown and overexpression of METTL3 notably decreased NSCLC cell viability, apoptosis and migration in vitro and, as well as tumorigenicity in vivo. Expression of METTL3 was upregulated in NSCLC tissue. METTL3 overexpression promoted cell viability and migration in NSCLC, while knockdown of METTL3 yielded the opposite result in vivo and in vitro. METTL3 increased Bcl-2 translation via m6A modification, which increased viability and enhanced migration of NSCLC cells. METTL3 served as an oncogene in NSCLC via METTL3-mediated Bcl-2 mRNA m6A modification, which indicated that targeting METTL3 may be an effective therapeutic strategy for clinical management of NSCLC.

show abstract

Analysis of METTL3 and METTL14 in hepatocellular carcinoma

Cited by 51 publications

References 43 publications

m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

m6A-Induced LncRNA MEG3 Suppresses the Proliferation, Migration and Invasion of Hepatocellular Carcinoma Cell Through miR-544b/BTG2 Signaling

METTL3‑mediated m6A modification of Bcl‑2 mRNA promotes non‑small cell lung cancer progression

Contact Info

Product

Resources

About