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Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation

  • Authors:
    • Weihua Zhu
    • Jiahui Feng
    • Yuanting Zhang
    • Qianqian Zhou
    • Herong Huang
    • Yu Yang
  • View Affiliations / Copyright

    Affiliations: Department of Basic Medical Sciences, Clinical College of Anhui Medical University, Hefei, Anhui 230031, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 531
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    Published online on: September 18, 2025
       https://doi.org/10.3892/ol.2025.15277
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Abstract

Ovarian cancer (OC) is a prevalent gynecological malignancy requiring advancements in treatment. Resveratrol (RES), a natural polyphenolic compound, has attracted widespread attention due to its potent anticancer properties. Long non‑coding (lnc)RNAs serve crucial regulatory roles in OC pathogenesis. However, the mechanism underlying the RES‑mediated inhibition of OC cell proliferation through lncRNA regulation is not fully understood. The present study aimed to assess the role of lncRNAs in RES‑mediated inhibition of OC cell growth. The A2780 OC cell line was used as the experimental model to establish control and RES‑treated groups. The effect of RES on OC cell migration was also evaluated. Differentially expressed lncRNAs (DELs) were identified after RES treatment. lncRNA‑mRNA regulatory networks of tumor‑related pathways were constructed and functionally assessed using reverse transcription‑quantitative PCR, proliferation assays, and knockdown and overexpression of hub lncRNAs. The results demonstrated that RES significantly inhibited OC cell migration. Moreover, 721 DELs were identified after RES treatment and were predominantly enriched in the p53 signaling pathway and cell cycle regulation associated with tumorigenesis. Key lncRNAs, including lnc‑small nucleolar RNA host gene 15 (SNHG15)‑203, demonstrated significant downregulation following RES treatment. Networks of tumor‑associated mRNAs and their target lncRNAs also revealed an association with lnc‑SNHG15‑203. Furthermore, functional validation demonstrated that lnc‑SNHG15‑203 suppression markedly reduced the expression of the downstream targets H2A clustered histone (H2AC)7 and H2AC20, inhibiting cell proliferation. These results were consistent with the antiproliferative effects observed in RES‑treated cells. Overall, the present study systematically characterized the lncRNA expression profiles associated with the RES‑mediated inhibition of cell proliferation, establishing lnc‑SNHG15‑203 as a critical mediator of the anti‑OC activity of RES. The findings could help to formulate strategies for improving OC treatment.
View Figures

Figure 1

Migration of resveratrol-treated
ovarian cancer cells assessed using Transwell assay (magnification,
×100; scale bar, 1 mm). **P<0.01.

Figure 2

lncRNA expression profiles of
RES-treated ovarian cancer cells. (A) Statistical analysis of
different types of lncRNA transcripts according to their genomic
locations. (B) Pearson's correlation analysis. (C) Volcano plot
depicting the DELs in the RES-treated and the control groups. (D)
Hierarchical clustering heatmap demonstrating the expression
profiles of DELs between RES-treated and control groups. Red, high
expression levels, the bluer one indicates lower expression levels.
lncRNA, long non-coding RNA; RES, resveratrol; DELs, differentially
expressed lncRNAs; C, control group; T, RES-treated group; FDR,
false discovery rate; FC, fold change.

Figure 3

Feature distribution comparison of
lncRNAs and mRNAs. (A) Exon number. (B) Transcript length. (C) ORF
length. (D) Expression levels of mRNA and lncRNA transcripts in
control and resveratrol-treated groups. (E) Abundance of
differential mRNA and lncRNA transcripts. (F) Encoding potential
scores of mRNA and lncRNA transcripts. ***P<0.001. lncRNA, long
non-coding RNA; ORF, open reading frame; C, control group; T,
resveratrol-treated group; TPM, transcripts per million.

Figure 4

Functional analysis of differentially
expressed lncRNAs. (A) GO, (B) KEGG pathway and (C) Reactome
enrichment analysis of differentially expressed cis-acting
lncRNAs. (D) GO, (E) KEGG pathway and (F) Reactome enrichment
analysis of differentially expressed trans-acting lncRNAs.
lncRNA, long non-coding RNA; GO, Gene Ontology; KEGG, Kyoto
Encyclopedia of Genes and Genomes.

Figure 5

Long non-coding RNA-mRNA networks.
CDKN1A, SQSTM1, H2AC7, H2AC20 and H2AC18 are hub
genes in the networks. CDKN1A, cyclin dependent kinase inhibitor
1A; SQSTM1, sequestosome 1; H2AC, H2A clustered histone.

Figure 6

RT-qPCR validation of long non-coding
RNA and mRNA expression in 75 µM resveratrol-treated ovarian cancer
cells. (A) RT-qPCR and RNA-seq quantification results of lncRNA.
Orange bars indicate RT-qPCR results, and blue lines indicate
RNA-seq results. (B) RT-qPCR results of mRNA expression.
*P<0.05; **P<0.01; ***P<0.001. RT-qPCR, reverse
transcription-quantitative PCR; RNA-seq, RNA-sequencing; TPM,
transcripts per million; ENO1, enolase 1; SNHG, small nucleolar RNA
host gene; VMP1, vacuole membrane protein 1; CDKN1A, cyclin
dependent kinase inhibitor 1A; SQSTM1, sequestosome 1; H2AC, H2A
clustered histone.

Figure 7

Effect of lnc-SNHG15-203 on
proliferation and target gene expression in ovarian cancer cells.
(A) Expression efficiency of siRNAs targeting
lnc-SNHG15-203. (B) Overexpression efficiency of
lnc-SNHG15-203. (C) Proliferation efficiency of A2780 cells
treated with siRNA and overexpression plasmid for
lnc-SNHG15-203, determined using Cell-Counting Kit-8 assays.
Relative expression levels of (D) H2AC7 and (E)
H2AC20 mRNA, determined using reverse
transcription-quantitative PCR. **P<0.01; ***P<0.001. lnc,
long non-coding; SNHG, small nucleolar RNA host gene; si, small
interfering; H2AC, H2A clustered histone; NC, negative control; OE,
overexpression.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu W, Feng J, Zhang Y, Zhou Q, Huang H and Yang Y: Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation. Oncol Lett 30: 531, 2025.
APA
Zhu, W., Feng, J., Zhang, Y., Zhou, Q., Huang, H., & Yang, Y. (2025). Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation. Oncology Letters, 30, 531. https://doi.org/10.3892/ol.2025.15277
MLA
Zhu, W., Feng, J., Zhang, Y., Zhou, Q., Huang, H., Yang, Y."Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation". Oncology Letters 30.5 (2025): 531.
Chicago
Zhu, W., Feng, J., Zhang, Y., Zhou, Q., Huang, H., Yang, Y."Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation". Oncology Letters 30, no. 5 (2025): 531. https://doi.org/10.3892/ol.2025.15277
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu W, Feng J, Zhang Y, Zhou Q, Huang H and Yang Y: Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation. Oncol Lett 30: 531, 2025.
APA
Zhu, W., Feng, J., Zhang, Y., Zhou, Q., Huang, H., & Yang, Y. (2025). Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation. Oncology Letters, 30, 531. https://doi.org/10.3892/ol.2025.15277
MLA
Zhu, W., Feng, J., Zhang, Y., Zhou, Q., Huang, H., Yang, Y."Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation". Oncology Letters 30.5 (2025): 531.
Chicago
Zhu, W., Feng, J., Zhang, Y., Zhou, Q., Huang, H., Yang, Y."Role of long non‑coding RNA‑mRNA interactions in resveratrol‑mediated inhibition of ovarian cancer cell proliferation". Oncology Letters 30, no. 5 (2025): 531. https://doi.org/10.3892/ol.2025.15277
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