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Long noncoding RNA LBX2-AS1-modulated miR-4766-5p regulates gastric cancer development through targeting CXCL5
LiPan Peng1, ZeZhong Chen2, GuangChuan Wang3
1Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, China.
Background:
Long noncoding RNAs (LncRNAs) have been reported to critically regulate gastric cancer (GC). Recently, it was reported that LBX2 antisense RNA 1 (LBX2-AS1) is abnormally expressed in GC. However, the role of LBX2-AS1 in the malignancy of GC is worth further discussion.
Methods:
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the LBX2-AS1, miR-4766-5p and C-X-C motif chemokine (CXCL5) expression in GC tissues and cells. Dual-luciferase reporter assay was applied to examine the target relationship between LBX2-AS1 and miR-4766-5p or miR-4766-5p and CXCL5. Cell counting kit-8 (CCK-8) and Transwell assays were used to detect cell proliferation, migration and invasion rates. The protein expression of CXCL5 was confirmed using western blot. The RNA pull down experiment was used to verify the specificity of LBX2-AS1 and miR-4766-5p on BGC-823 and SGC-7901 cells.
Results:
LBX2-AS1 was up-regulated in GC tissues and cells, and its knockdown suppressed proliferation, migration and invasion of GC cells. While, overexpression of LBX2-AS1 increased proliferation and increased CXCL5 mRNA level. CXCL5 improved cell proliferation, migration and invasion of GC cells. LBX2-AS1 could bind to miR-4766-5p to regulate CXCL5 expression. Overexpression of CXCL5 overturned those effects of miR-4766-5p in GC cells. RNA Pull down shown that BGC-823 and SGC-7901 cells, miR-4766-5p specifically binds to LBX2-AS1.
Conclusions:
In short, this study demonstrated that LBX2-AS1 promoted proliferation, migration and invasion through up-regulation CXCL5 mediated by miR-4766-5p in GC. The LBX2-AS1/miR-4766-5p/CXCL5 regulatory axis provides a theoretical basis for the research on lncRNA-directed therapeutics in GC.
Insights
This study reveals that long noncoding RNA LBX2-AS1 promotes gastric cancer (GC) progression by increasing C-X-C motif chemokine CXCL5 via miR-4766-5p. This LBX2-AS1/miR-4766-5p/CXCL5 pathway offers a therapeutic target for GC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (LncRNAs) play a crucial role in gastric cancer (GC) development.
- LBX2 antisense RNA 1 (LBX2-AS1) expression is altered in GC, necessitating further investigation into its oncogenic functions.
Purpose of the Study:
- To elucidate the role of LBX2-AS1 in gastric cancer (GC) malignancy.
- To investigate the molecular mechanism underlying LBX2-AS1's function in GC progression.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to assess expression levels of LBX2-AS1, miR-4766-5p, and CXCL5.
- Dual-luciferase reporter assays to confirm targeting interactions between LBX2-AS1, miR-4766-5p, and CXCL5.
- Cell proliferation, migration, and invasion assays (CCK-8, Transwell) and Western blot to evaluate cellular functions and protein expression.
Main Results:
- LBX2-AS1 was significantly upregulated in GC tissues and cells, correlating with increased proliferation, migration, and invasion.
- LBX2-AS1 directly targets miR-4766-5p, leading to the upregulation of C-X-C motif chemokine CXCL5.
- CXCL5 overexpression promoted GC cell proliferation, migration, and invasion, while miR-4766-5p suppressed these effects.
Conclusions:
- LBX2-AS1 promotes GC cell proliferation, migration, and invasion by upregulating CXCL5 through the miR-4766-5p pathway.
- The identified LBX2-AS1/miR-4766-5p/CXCL5 axis presents a potential therapeutic strategy for gastric cancer.
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