Dataset Information

N6-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.

ABSTRACT: N6-methyladenosine (m6A) serves as the most common and conserved internal transcriptional modification. However, the roles of m6A on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely correlated with the lymph node metastasis and poor prognosis of CC patients. MeRIP-Seq analysis revealed the m6A profiles in CC cells. Functionally, METTL3 promoted the proliferation and Warburg effect (aerobic glycolysis) of CC cells. Mechanistically, METTL3 targeted the 3'-Untranslated Region (3'-UTR) of hexokinase 2 (HK2) mRNA. Moreover, METTL3 recruited YTHDF1, a m6A reader, to enhance HK2 stability. These findings demonstrated that METTL3 enhanced the HK2 stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which might promote a novel insight for the CC treatment.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7585578 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

N6-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.

Wang Qianqing Q Guo Xiangcui X Li Li L Gao Zhihui Z Su Xiaoke X Ji Mei M Liu Juan J

Cell death & disease 20201024 10

N6-methyladenosine (m6A) serves as the most common and conserved internal transcriptional modification. However, the roles of m6A on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely correlated with the lymph node metastasis and poor prognosis of CC patients. MeRIP-Seq analysis revealed the m6A profiles in CC cells. Functionally, METTL3 promoted the pro ...[more]

PMID: 33099572

Similar Datasets

Project description:BackgroundAs an important N6-methyladenosine (m6A) regulator, abnormal expression of methyltransferase-like protein 3 (METTL3) has been reported in certain human cancers. Although some data have shown that METTL3 plays an essential role in the progression of clear-cell renal cell carcinoma RCC (ccRCC), the detailed mechanism still remains largely undetermined.MethodsImmunohistochemistry (IHC) assay was used to examine the expression of METTL3 and its clinical implications in human ccRCC by using tissue-microarray (TMA). The cellular models based on ccRCC cell lines such as 786-O and ACHN, were established by operating METTL3 and HHLA2 via knockdown or overexpression, followed by in vitro cellular function studies and in vivo subcutaneous transplantation tumor model.ResultsWe found that METTL3 expression in ccRCC tissues was significantly higher compared with adjacent normal tissues. We also found the overall survival (OS) of the patients with low METTL3 expression was significantly better compared with the patients with high METTL3 expression. Furthermore, HHLA2highMETTL3high could serve as a better prognostic predictor for ccRCC patients. Depletion of METTL3 could significantly inhibit the cell viability, migration, and invasion abilities in ccRCC cell lines. Cellular studies further revealed that METTL3 could regulate HHLA2 expression via m6A modification of HHLA2 mRNA. In vitro studies revealed that HHLA2 overexpression could reverse the inhibition of cellular functions mediated by METTL3 depletion. The subcutaneous transplantation tumor model confirmed that HHLA2 overexpression could reverse the inhibition of tumor growth mediated by METTL3 depletion.ConclusionOur study indicated that METTL3 served as an important prognostic predictor for ccRCC patients, and we demonstrated a novel regulatory mechanism of HHLA2 by mRNA epigenetic modification via METTL3. Moreover, we found that the METTL3/HHLA2 axis could promote tumorigenesis of ccRCC. Collectively, our current findings provided new insights into the therapeutic strategy against this malignancy targeting METTL3.

Dataset Information

N6-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.

Publications

N<sup>6</sup>-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

N6-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.

Publications

N&lt;sup&gt;6&lt;/sup&gt;-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

N<sup>6</sup>-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification.