METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m6 A Modification

Molecular Therapy. Nucleic Acids
Wei ZhaoJie Wu

Abstract

N6-Methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N6 nitrogen of adenosine. However, the roles of m6A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (METTL3) in OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated in tissue samples and correlated with the poor prognosis of OSCC patients. Functionally, loss and gain studies illustrated that METTL3 promoted the proliferation, invasion, and migration of OSCC cells in vitro, and METTL3 knockdown inhibited tumor growth in vivo. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that METTL3 targeted the 3' UTR (near to stop codon) of the c-Myc transcript to install the m6A modification, thereby enhancing its stability. Furthermore, results revealed that YTH N6-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m6A-increased stability of c-Myc mRNA catalyzed by METTL3. In conclusion, our findings herein identify that METTL3 accelerates the c-Myc stability via YTHDF1-mediated m6A modification, thereby giving rise to OSCC tumorigenesis.

Citations

Aug 26, 2020·Molecular Biotechnology·R Karthiya, Piyush Khandelia
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Yang LiRuipeng Jia
Aug 29, 2020·Journal of Hematology & Oncology·Chengwu ZengHengyou Weng
Sep 23, 2020·International Journal of Molecular Sciences·Jonas WeißeTony Gutschner
Jan 5, 2021·Infection·Alexandra BinniePedro Castelo-Branco
Dec 31, 2020·Diagnostics·Kamila RomanowskaWojciech Golusiński
Dec 8, 2020·Frontiers in Oncology·Chunyue FengJianhua Mao
Apr 3, 2021·Cell Death & Disease·Rongkai ShiHongchuan Jin
Apr 15, 2021·Cell Metabolism·Harini RamalingamVishal Patel
Apr 22, 2021·Biomarker Research·Yiqing CaiXin Wang
Jun 22, 2021·Journal of Clinical Laboratory Analysis·Yanfei LiuJun Bian
Jul 25, 2021·Cancers·Eun Kyung Ko, Brian C Capell
Jul 29, 2021·Journal of Hematology & Oncology·Wei HuangYue-Qin Chen
Aug 3, 2021·Cancer Letters·Bing HanXiangwei Gao
Aug 18, 2021·The Journal of Experimental Medicine·Amalie C GrenovZiv Shulman
Aug 28, 2021·Journal of Experimental & Clinical Cancer Research : CR·Vera Miranda-GonçalvesCarmen Jerónimo
Sep 18, 2021·Clinical Epigenetics·Alessia IaizaFrancesco Fazi
Sep 22, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zishan PengHaipeng Xiao
Oct 25, 2021·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Shuangjiang WuSuttichai Krisanaprakornkit
Jan 14, 2022·Molecular Cancer·Yuanyuan An, Hua Duan

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
MeRIP-seq
transfection
Dot blot
xenograft
PCR
protein assay
dot blots

Software Mentioned

Integrative Genomics Viewer ( IGV )
SPSS
METTL3
GraphPad

Related Concepts

Related Feeds

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.