Dataset Information

Novel evidence for m⁶A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.

ABSTRACT:

Background

While emerging evidence indicates that N⁶-methyladenosine (m⁶A) regulators play crucial roles in cancer progression, their clinical significance in gastric cancer (GC) has thus far not been elucidated.

Methods

We investigated the expression of the m⁶A regulator genes and their prognostic potential in a large clinical cohort of 173 GC patients using qRT-PCR assays. In addition, we undertook a series of in-vitro and in-vivo functional studies to investigate the oncogenic role of FTO.

Results

GC patients with low expression of METTL3, METTL14, ALKBH5, WTAP and YTHDF1 demonstrated significantly poor OS, while patients with high FTO expression exhibited markedly worse OS. Furthermore, the cumulative risk-score derived from these gene panel also significantly associated with poor OS, with a corresponding hazard ratio of 5.47 (95% CI: 3.18-9.41, p < 0.0001). We observed that FTO expression was frequently upregulated in GC cell lines, with epithelial-mesenchymal-transition (EMT) features. FTO knockdown in HGC27 and AGS cells inhibited cell proliferation and migratory potential, while its overexpression in MKN28 cells resulted in enhanced proliferation and migration. Finally, confirming our in-vitro findings, FTO suppression led to significant tumour growth inhibition in a HGC27 xenograft model.

Conclusions

We demonstrate that m⁶A regulators may serve as promising prognostic biomarkers in GC. Our functional studies reveal that FTO is an important oncogene and may be a promising therapeutic target associated with EMT-alterations in gastric cancer.

SUBMITTER: Shimura T

PROVIDER: S-EPMC8770595 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Novel evidence for m<sup>6</sup>A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.

Shimura Tadanobu T Kandimalla Raju R Okugawa Yoshinaga Y Ohi Masaki M Toiyama Yuji Y He Chuan C Goel Ajay A

British journal of cancer 20211021 2

<h4>Background</h4>While emerging evidence indicates that N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) regulators play crucial roles in cancer progression, their clinical significance in gastric cancer (GC) has thus far not been elucidated.<h4>Methods</h4>We investigated the expression of the m<sup>6</sup>A regulator genes and their prognostic potential in a large clinical cohort of 173 GC patients using qRT-PCR assays. In addition, we undertook a series of in-vitro and in-vivo functional stud ...[more]

PMID: 34675398

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Dataset Information

Novel evidence for m⁶A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.

Background

Methods

Results

Conclusions

Publications

Novel evidence for m<sup>6</sup>A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Novel evidence for m6A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.

Background

Methods

Results

Conclusions

Publications

Novel evidence for m<sup>6</sup>A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Novel evidence for m⁶A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.