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Peer-reviewedCC BY 4.0Scientific Reports

AFAP1-AS1/miR-195-5p is associated with malignant phenotypes and glycolysis-related metabolic changes in hepatocellular carcinoma

  • Peng Gu
  • Weixin Ren
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Abstract

The long noncoding RNA AFAP1-AS1 is aberrantly expressed in multiple solid tumors, but its functional role in hepatocellular carcinoma (HCC) remains incompletely characterized. In this study, analysis of the TCGA-LIHC cohort and eight paired HCC and matched adjacent non-tumor tissues showed that AFAP1-AS1 was upregulated in HCC and associated with poorer overall survival in the TCGA cohort. Knockdown of AFAP1-AS1 inhibited the proliferation, migration, and invasion of HCC cells. Bioinformatic prediction, expression analysis, and dual-luciferase reporter assays supported a possible regulatory relationship between AFAP1-AS1 and miR-195-5p at the predicted binding site. Inhibition of miR-195-5p increased FOXK1 expression, consistent with the effectiveness of miR-195-5p inhibition, and enhanced HCC cell migration and invasion. It also increased glucose consumption and lactate production, indicating glycolysis-related metabolic changes. Exploratory RNA-seq analysis after miR-195-5p inhibition, integrated with FOXK1 target genes and a glycolysis-related gene set, identified four candidate genes. However, these candidates and the role of FOXK1 in mediating the observed phenotypes were not functionally validated. Rescue experiments showed that miR-195-5p inhibition partially reversed the suppressive effects of AFAP1-AS1 knockdown on HCC cell proliferation, migration, and invasion. In addition, inhibition of miR-195-5p promoted tumor growth in a HCC xenograft model. Overall, these findings suggest a possible association of AFAP1-AS1 and miR-195-5p with malignant phenotypes and glycolysis-related metabolic changes in HCC.

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Cite

BibTeXRIS
BibTeX
@article{gu2026afap1as1mir1955p,
  title = {{AFAP1-AS1/miR-195-5p is associated with malignant phenotypes and glycolysis-related metabolic changes in hepatocellular carcinoma}},
  author = {Peng Gu and Weixin Ren},
  journal = {Scientific Reports},
  year = {2026},
  month = oct,
  doi = {10.1038/s41598-026-76653-z},
  url = {https://www.nature.com/articles/s41598-026-76653-z},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - AFAP1-AS1/miR-195-5p is associated with malignant phenotypes and glycolysis-related metabolic changes in hepatocellular carcinoma
AU  - Peng Gu
AU  - Weixin Ren
PY  - 2026
DA  - 2026/10/15
JO  - Scientific Reports
DO  - 10.1038/s41598-026-76653-z
UR  - https://www.nature.com/articles/s41598-026-76653-z
AB  - The long noncoding RNA AFAP1-AS1 is aberrantly expressed in multiple solid tumors, but its functional role in hepatocellular carcinoma (HCC) remains incompletely characterized. In this study, analysis of the TCGA-LIHC cohort and eight paired HCC and matched adjacent non-tumor tissues showed that AFAP1-AS1 was upregulated in HCC and associated with poorer overall survival in the TCGA cohort. Knockdown of AFAP1-AS1 inhibited the proliferation, migration, and invasion of HCC cells. Bioinformatic prediction, expression analysis, and dual-luciferase reporter assays supported a possible regulatory relationship between AFAP1-AS1 and miR-195-5p at the predicted binding site. Inhibition of miR-195-5p increased FOXK1 expression, consistent with the effectiveness of miR-195-5p inhibition, and enhanced HCC cell migration and invasion. It also increased glucose consumption and lactate production, indicating glycolysis-related metabolic changes. Exploratory RNA-seq analysis after miR-195-5p inhibition, integrated with FOXK1 target genes and a glycolysis-related gene set, identified four candidate genes. However, these candidates and the role of FOXK1 in mediating the observed phenotypes were not functionally validated. Rescue experiments showed that miR-195-5p inhibition partially reversed the suppressive effects of AFAP1-AS1 knockdown on HCC cell proliferation, migration, and invasion. In addition, inhibition of miR-195-5p promoted tumor growth in a HCC xenograft model. Overall, these findings suggest a possible association of AFAP1-AS1 and miR-195-5p with malignant phenotypes and glycolysis-related metabolic changes in HCC.
SN  - 2045-2322
ER  -