The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
ALKBH5 suppresses malignancy of hepatocellular carcinoma via m6A-guided epigenetic inhibition of LYPD1
Open accessAbstract
Background: N6-methyladenosine (m 6 A) modification is an emerging layer of epigenetic regulation which is widely implicated in the tumorigenicity of hepatocellular carcinoma (HCC), offering a novel perspective for investigating molecular pathogenesis of this disease. The role of AlkB homolog 5 (ALKBH5), one of the m 6 A demethylases, has not been fully explored in HCC. Here we clarify the biological profile and potential mechanisms of ALKBH5 in HCC. Methods: Expression of ALKBH5 and its correlation with clinicopathological characteristics of HCC were evaluated using tissue microarrays and online datasets. And biological effects of ALKBH5 in HCC were determined in vitro and in vivo. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA sequencing (RNA-seq), and following m 6 A dot blot, MeRIP-qPCR, RIP-qPCR or dual luciferase reporter assays were employed to screen and validate the candidate targets of ALKBH5. Results: We demonstrated that ALKBH5 was down-regulated in HCC, and decreased ALKBH5 expression was an independent prognostic factor of worse survival in HCC patients. Functionally, ALKBH5 suppressed the proliferation and invasion capabilities of HCC cells in vitro and in vivo. Mechanistically, ALKBH5-mediated m 6 A demethylation led to a post-transcriptional inhibition of LY6/PLAUR Domain Containing 1 (LYPD1), which could be recognized and stabilized by the m 6 A effector IGF2BP1. In addition, we identified that LYPD1 induced oncogenic behaviors of tumors in contrast to ALKBH5. Dysregulation of ALKBH5/LYPD1 axis impelled the progression of HCC. Conclusion: Our study reveals that ALKBH5, characterized as a tumor suppressor, attenuates the expression of LYPD1 via an m 6 A-dependent manner in HCC cells. Our findings enrich the landscape of m 6 A-modulated tumor malignancy, and provide new insights into potential biomarkers and therapeutic targets of HCC treatment.
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1 retracted
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A global view of hepatocellular carcinoma: trends, risk, prevention and management
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N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
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“The canonical complex of writers called “WMM” is comprised of methyltransferaselike 3 (METTL3), methyltransferase-like 14 (METTL14) and Wilms tumor 1-associated protein (WTAP) [7], while identified erasers consist of fat-mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5) [8, 9].”
AKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility
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Differential analysis of gene regulation at transcript resolution with RNA-seq
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Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation
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Cited by
Wu, S., Yun, J., Tang, W., Familiari, G., Relucenti, M., Wu, J., Li, X., Chen, H., & Chen, R. (2023) · ACS Nano · doi:10.1021/acsnano.3c03050 · Cited by 102
Self-citationHan, S., Xue, L., Wei, Y., Yong, T., Jia, W., Qi, Y., Luo, Y., Liang, J., Wen, J., Bie, N., et al. (2023) · Advanced Science · doi:10.1002/advs.202207080 · Cited by 24
Bi, X., Ma, B., Liu, W., Gao, W.-Q., Ye, J., & Rao, H. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-04109-0 · Cited by 7
Metadata
- Authors
- Chen, Y., Zhao, Y., Chen, J., Peng, C., Zhang, Y., Tong, R., Cheng, Q., Yang, B., Feng, X., Lu, Y., Xie, H., Zhou, L., Wu, J., & Zheng, S.
- Venue
- Molecular Cancer
- Published
- 2020-08-10
- Volume
- 19
- Issue
- 1
- Pages
- 123-123
- ISSN
- 1476-4598 (ISSN-L)
- OpenAlex
- W3048858129
- Cited by
- 284
- References
- 49
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- gold
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- Chen, Y., Zhao, Y., Chen, J., Peng, C., Zhang, Y., Tong, R., Cheng, Q., Yang, B., Feng, X., Lu, Y., Xie, H., Zhou, L., Wu, J., & Zheng, S. (2020). ALKBH5 suppresses malignancy of hepatocellular carcinoma via m6A-guided epigenetic inhibition of LYPD1. Molecular Cancer. https://doi.org/10.1186/s12943-020-01239-w
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