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Published on: September 15, 2023
Decreased expression of the long non-coding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 and
Lin Yao1, Peng-Cheng Ye2, Wang Tan3
1Department of Gastrointestinal Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China, The Hepatobiliary Research Institute, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
Background:
Long non-coding RNAs (lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer (GC) has not been fully elucidated.
Aim:
To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC.
Methods:
Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pcHOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXD-AS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.
Results:
The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.
Conclusion:
These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.
Insights
Downregulation of the long non-coding RNA HOXD-AS2 promotes gastric cancer (GC) progression by affecting HOXD8 expression and the PI3K/Akt pathway. HOXD-AS2 may serve as a diagnostic biomarker and therapeutic target for GC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) play roles in various cancers, but their specific functions in gastric cancer (GC) remain unclear.
- Investigating lncRNAs like HOXD-AS2 is crucial for understanding GC development.
Purpose of the Study:
- To investigate the expression, molecular mechanism, and prognostic significance of HOXD-AS2 in gastric cancer.
- To determine if HOXD-AS2 can serve as a diagnostic biomarker or therapeutic target for GC.
Main Methods:
- Real-time quantitative PCR to assess HOXD-AS2 expression in GC tissues and cell lines.
- In vitro assays (Transwell, wound healing, CCK-8, flow cytometry) to evaluate HOXD-AS2's impact on GC cell proliferation, migration, invasion, cell cycle, and apoptosis.
- Western blot analysis to explore the regulatory mechanism involving HOXD8 and the PI3K/Akt pathway.
Main Results:
- Low HOXD-AS2 expression correlated with lymph node metastasis and advanced tumor-node-metastasis stage in GC.
- Overexpression of HOXD-AS2 inhibited GC cell progression, proliferation, and migration.
- HOXD-AS2 was found to regulate HOXD8 expression and inhibit the PI3K/Akt signaling pathway.
Conclusions:
- Downregulation of HOXD-AS2 promotes GC progression by modulating HOXD8 expression and activating the PI3K/Akt pathway.
- HOXD-AS2 shows potential as a novel diagnostic biomarker and therapeutic target for gastric cancer.
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