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JHDM1D-AS1 aggravates the development of gastric cancer through miR-450a-2-3p-PRAF2 axis
Min Wu1, Yi Liu2, Yan-Song Pu3
1Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China; Office of Scientific Research, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
Aims:
To investigate the molecular function and mechanisms of JHDM1D antisense 1 (JHDM1D-AS1) during gastric cancer (GC) progression.
Materials And Methods:
The qPCR assay was used to detect the JHDM1D-AS1 and miR-450a-2-3p expression levels in GC tissues and cell lines. Bioinformatics analysis was used for exploring the lncRNA-microRNA-mRNA interaction network. We performed dual-luciferase reporter assay and qPCR assay in order to validate the direct interactions. We explored the JHDM1D-AS1 and miR-450a-2-3p on GC progression by using JHDM1D-AS1 siRNA and miR-450a-2-3p inhibitor; in vitro CCK-8 assay, colony formation assay, and invasion assay were conducted. Further, in vivo animal experiments were performed, and the expression levels of miR-450a-2-3p and PRAF2 in the tumor tissues were detected using qPCR and western blot analysis.
Key Findings:
The expression levels of JHDM1D-AS1 and miR-450a-2-3p in GC tissues and cell lines were higher and lower as compared to those in the corresponding normal controls, respectively. Moreover, high levels of JHDM1D-AS1 were closely related with metastasis and the GC TNM stage. Functionally, JHDM1D-AS1 depletion caused an obvious reduction in cell proliferation and invasion both in vitro and in vivo, while the addition of miR-450a-2-3p inhibitor could nullify these effects. Mechanically, JHDM1D-AS1 promoted GC progression via the sponging of miR-450a-2-3p in order to increase PRAF2 expression.
Significance:
The present results showed that the increased expression of JHDM1D-AS1 was closely associated with tumor progression of GC. JHDM1D-AS1/miR-450a-2-3p/PRAF2 axis may be a promising target for GC treatment.
Insights
Gastric cancer progression is linked to increased JHDM1D-AS1. This long non-coding RNA promotes cancer by sponging miR-450a-2-3p, increasing PRAF2, and may be a therapeutic target.
Area of Science:
- Molecular biology
- Oncology
- Genetics
Background:
- Gastric cancer (GC) remains a significant health challenge globally.
- Understanding the molecular mechanisms driving GC progression is crucial for developing effective treatments.
Purpose of the Study:
- To elucidate the role and molecular mechanisms of JHDM1D-AS1 in gastric cancer progression.
- To investigate the regulatory axis involving JHDM1D-AS1, miR-450a-2-3p, and PRAF2 in GC.
Main Methods:
- Quantitative PCR (qPCR) to assess gene expression.
- Bioinformatics analysis to predict molecular interactions.
- Dual-luciferase reporter assays to confirm direct interactions.
- In vitro and in vivo experiments using siRNA and inhibitors to evaluate functional impact.
- Western blot analysis for protein expression detection.
Main Results:
- JHDM1D-AS1 expression was upregulated in GC tissues and cell lines.
- High JHDM1D-AS1 levels correlated with GC metastasis and TNM stage.
- JHDM1D-AS1 depletion inhibited GC cell proliferation and invasion.
- JHDM1D-AS1 sponges miR-450a-2-3p, leading to increased PRAF2 expression.
Conclusions:
- JHDM1D-AS1 promotes gastric cancer progression.
- The JHDM1D-AS1/miR-450a-2-3p/PRAF2 axis represents a potential therapeutic target for GC.
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