Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 18;14(1):tfae209.
doi: 10.1093/toxres/tfae209. eCollection 2025 Feb.

ALKBH5 knockdown suppresses gastric cancer progression by reducing the expression of long non-coding RNA TUG1

Peng Fan  1   2   3   4 , Yu-Jie Huang  5 , Xiang-Yu Xie  2 , Liu-Hua Wang  1   3   4 , Bin Liu  1   3   4 , Dao-Rong Wang  1   3   4
Affiliations

ALKBH5 knockdown suppresses gastric cancer progression by reducing the expression of long non-coding RNA TUG1

Peng Fan et al. Toxicol Res (Camb). .

Abstract

Purpose: This study aimed to explore the relationship between m6A demethylase ALKBH5 and long noncoding RNA TUG1 (TUG1), as well as their effects on proliferation, migration, and angiogenesis in gastric cancer (GC) cells.

Methods: The Cancer Genome Atlas (TCGA) database was utilized to analyze the relative expression levels of ALKBH5, TUG1, and vascular endothelial growth factor A (VEGFA). Survival analyses of TUG1, ALKBH5, and VEGFA were performed using the Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier databases. The binding sites of TUG1 and ALKBH5 were predicted using the Annolnc2 database. The correlation between ALKBH5 and TUG1 expression was analyzed using the GEPIA database. Subsequently, small interfering RNA (siRNA) targeting ALKBH5 and TUG1 was transfected into SGC-7901 cells, and functional studies were conducted using quantitative real-time polymerase chain reaction (qRT-PCR), CCK-8 assays, colony formation assays, transwell assays, and angiogenesis assays.

Results: Bioinformatics analysis indicated that ALKBH5, TUG1, and VEGFA were highly expressed in gastric cancer tissues and exhibited a positive correlation. Survival analysis revealed that high expression levels of ALKBH5, TUG1, and VEGFA were significantly associated with poor prognosis in gastric cancer patients. Binding sites for TUG1 and ALKBH5 were identified. Functional experiments demonstrated that the knockdown of ALKBH5 resulted in the downregulation of TUG1, which subsequently reduced the proliferation, invasion, migration, and angiogenesis of gastric cancer cells.

Conclusion: The m6A demethylase ALKBH5 promotes gastric cancer progression by erasing the methylation modification of TUG1 and increasing TUG1 expression. This finding provides a new perspective for the treatment and prognosis assessment of gastric cancer.

Keywords: ALKBH5; Angiogenesis; Gastric cancer; LncRNA-TUG1; Invasion; Migration.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020:396(10251):635–648. - PubMed
    1. Zhang X, Xie K, Zhou H, Wu Y, Li C, Liu Y, Liu Z, Xu Q, Liu S, Xiao D, et al. Role of non-coding RNAs and RNA modifiers in cancer therapy resistance. Mol Cancer. 2020:19(1):47. - PMC - PubMed
    1. Strong VE, Wu AW, Selby LV, Gonen M, Hsu M, Song KY, Park CH, Coit DG, Ji JF, Brennan MF. Differences in gastric cancer survival between the U.S. and China. J Surg Oncol. 2015:112(1):31–37. - PMC - PubMed
    1. Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, Sahmoud T, Shen L, Yeh KH, Chin K, et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013:31(31):3935–3943. - PMC - PubMed
    1. Bi Z, Liu Y, Zhao Y, Yao Y, Wu R, Liu Q, Wang Y, Wang X. A dynamic reversible RNA N(6) -methyladenosine modification: current status and perspectives. J Cell Physiol. 2019:234(6):7948–7956. - PubMed

LinkOut - more resources