Dataset Information

M⁶A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC.

ABSTRACT:

Background

The importance of mRNA methylation erased by ALKBH5 in mRNA biogenesis, decay, and translation control is an emerging research focus. Ectopically activated YAP is associated with the development of many human cancers. However, the mechanism whereby ALKBH5 regulates YAP expression and activity to inhibit NSCLC tumor growth and metastasis is not clear.

Methods

Protein and transcript interactions were analyzed in normal lung cell and NSCLC cells. Gene expression was evaluated by qPCR and reporter assays. Protein levels were determined by immunochemical approaches. Nucleic acid interactions and status were analyzed by immunoprecipitation. Cell behavior was analyzed by standard biochemical tests. The m⁶A modification was analyzed by MeRIP.

Results

Our results show that YAP expression is negatively correlated with ALKBH5 expression and plays an opposite role in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. ALKBH5 reduced m⁶A modification of YAP. YTHDF3 combined YAP pre-mRNA depending on m⁶A modification. YTHDF1 and YTHDF2 competitively interacted with YTHDF3 in an m⁶A-independent manner to regulate YAP expression. YTHDF2 facilitated YAP mRNA decay via the AGO2 system, whereas YTHDF1 promoted YAP mRNA translation by interacting with eIF3a; both these activities are regulated by m⁶A modification. Furthermore, ALKBH5 decreased YAP activity by regulating miR-107/LATS2 axis in an HuR-dependent manner. Further, ALKBH5 inhibited tumor growth and metastasis in vivo by reducing the expression and activity of YAP.

Conclusions

The presented findings suggest m⁶A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Moreover, effective inhibition of m⁶A modification of ALKBH5 might constitute a potential treatment strategy for lung cancer.

SUBMITTER: Jin D

PROVIDER: S-EPMC7045432 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

m<sup>6</sup>A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC.

Jin Dan D Guo Jiwei J Wu Yan Y Yang Lijuan L Wang Xiaohong X Du Jing J Dai Juanjuan J Chen Weiwei W Gong Kaikai K Miao Shuang S Li Xuelin X Sun Hongliang H

Molecular cancer 20200227 1

<h4>Background</h4>The importance of mRNA methylation erased by ALKBH5 in mRNA biogenesis, decay, and translation control is an emerging research focus. Ectopically activated YAP is associated with the development of many human cancers. However, the mechanism whereby ALKBH5 regulates YAP expression and activity to inhibit NSCLC tumor growth and metastasis is not clear.<h4>Methods</h4>Protein and transcript interactions were analyzed in normal lung cell and NSCLC cells. Gene expression was evalua ...[more]

PMID: 32106857

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Dataset Information

M⁶A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC.

Background

Methods

Results

Conclusions

Publications

m<sup>6</sup>A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

M6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC.

Background

Methods

Results

Conclusions

Publications

m<sup>6</sup>A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁶A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC.