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Expression profiles of lncRNAs and mRNAs in AGS cells treated with O-prenylchalcone 7e

ABSTRACT: This study aimed to characterize the changes in lncRNA and mRNA expression profiles induced by O-prenylchalcone 7e in AGS gastric cancer cells. Background: Gastric cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the need to identify novel therapeutic strategies targeting the molecular networks involved in tumor progression. Although new therapeutic compounds show promising properties, the antitumor mechanisms activated by noncoding RNAs (ncRNAs) remain largely unexplored. In this study, we evaluated the effects of the novel compound O-prenylchalcone 7e on proliferation and cell death, with a particular focus on the transcriptome reprogramming mediated by long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) networks in gastric cancer cells. Methods: AGS cells were treated with O-prenylchalcone 7e and subjected to transcriptomic analysis of mRNAs and lncRNAs using Clariom™ D Human microarrays. Differentially expressed transcripts were analyzed by functional enrichment using GO, KEGG, and GSEA tools. LncRNA–miRNA–mRNA networks were constructed through co-expression analysis using Cytoscape. Candidate lncRNAs and mRNA expression were validated by RT-qPCR assays. LncRNA OVCH1-AS1 silencing was achieved by transfection of specific siRNAs. MiR-181a-5p ectopic overexpression was performed by transfection of the miRNA precursor. OVCH1-AS1 silencing and miR-181a-5p overexpression were assessed by RT-qPCR assays. RHOB protein levels were determined by Western blot. Cell proliferation was evaluated using MTT assays. Apoptosis analysis was performed via Annexin V/7-AAD staining and flow cytometry. Mitochondrial membrane potential was analyzed using the MitoOrange dye and flow cytometry. Results: Our data showed that O-prenylchalcone 7e reprogrammed the lncRNAs and mRNA transcriptome of AGS gastric cancer cells. Expression profiling using microarrays identified 261 differentially expressed lncRNAs, of which 146 were upregulated and 115 were downregulated following 48 h treatment with O-prenylchalcone 7e (IC50 49.15 μM). Moreover, 221 mRNAs were differentially expressed, including 56 upregulated and 165 downregulated transcripts. Enrichment and correlation analyses revealed that the upregulated lncRNAs, including OVCH1-AS1, NORAD, MIR4435-2HG, DKK4-1, and PAQR9-2, as well as the overexpressed mRNAs RHOB, BCL10, DDIT3, CSNK2A3, and FZD5, among others, were associated with processes related to apoptosis and cancer-related signaling pathways. Interestingly, we identified a novel OVCH1-AS1/miR-181a-5p/RHOB axis as a potential module regulated by O-prenylchalcone 7e. RT-qPCR assays confirmed the modulation of the OVCH1-AS1/miR-181a-5p/RHOB axis in AGS and NCI-N87 gastric cancer cells. Interestingly, OVCH1-AS1 silencing increased miR-181a-5p levels, whereas miR-181a-5p overexpression significantly reduced RHOB at mRNA and protein levels. Western blot experiments confirmed that O-prenylchalcone 7e increased RHOB protein, whereas OVCH1-AS1 silencing or miR-181a-5p overexpression also reduced RHOB levels. Remarkably, silencing of OVCH1-AS1 and overexpression of miR-181a-5p partially reversed the antiproliferative effects induced by O-prenylchalcone 7e in AGS and NCI-N87 cancer cells. Furthermore, both strategies reduced the compound-induced cell death, decreasing the apoptotic population. Finally, OVCH1-AS1-deficient cells and miR-181a-5p-overexpressing cancer cells showed a significant attenuation of the depolarization of the mitochondrial membrane in response to drug treatment. Conclusions: Our data suggest that O-prenylchalcone 7e induces a transcriptional remodeling in gastric cancer cells, involving the regulation of lncRNA/mRNA-mediated regulatory networks. The identification of the OVCH1-AS1/miR-181a-5p/RHOB axis reveals a potential ncRNA-dependent mechanism associated with the anticancer response induced by the drug. These findings expand our understanding of the role of lncRNAs in the molecular mechanisms underlying bioactive compounds and ultimately suggest a therapeutic potential of O-prenylchalcone 7e as a candidate drug for the development of novel strategies against gastric cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE344582 | GEO | 2026/09/30

REPOSITORIES: GEO

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Expression profiles of lncRNAs and mRNAs in AGS cells treated with O-prenylchalcone 7e

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