Long noncoding RNA HOTAIRM1 inhibits cell progression by regulating miR-17-5p/ PTEN axis in gastric cancer
Ruiqi Lu1, Gang Zhao1, Yulong Yang1
1Department of General Surgery, East Hospital of Tongji University, Shanghai, China.
Objectives:
This study was conducted to identify the significantly altered long noncoding RNAs (lncRNAs), messenger RNA (mRNA) and pathways in gastric cancer (GC).
Methods:
We used microarray analysis to identify differentially expressed lncRNAs and mRNAs, whereas the obviously changed pathways were found by gene set enrichment analysis. The coexpression network of lncRNA and mRNA was constructed by Cytoscape, and their target relationships with miRNAs were predicted by miRcode and TargetScan. qRT-PCR and Western blot were performed to determine the expression levels of mRNAs and proteins in tissues and cell lines. Dual-luciferase reporter assay was applied to achieve the determination of the specific target relationships. Cell viability, migration, and apoptosis were detected by MTT assay, wound healing assay and flow cytometry, respectively. Through the xenograft assay, the gastric tumor was implanted into nude mice to investigate the influence of HOTAIRM1 in vivo.
Results:
HOTAIRM1 and phosphatase and tensin homolog (PTEN) were both downregulated in GC, whereas miR-17-5p was upregulated. Moreover, the PI3K/AKT pathway was found activated in GC. HOTAIRM1 targeted miR-17-5p, whereas PTEN was the downstream target gene of miR-17-5p. HOTAIRM1 suppressed proliferation and migration of GC cell line and induced their apoptosis, whereas miR-17-5p played the opposite role on GC cell line. HOTAIRM1 also postponed tumor growth in vivo and inhibited the PI3K/AKT pathway in GC.
Conclusions:
LncRNA HORAIRM1 suppressed the PI3K/AKT pathway in GC and inhibited the progression of GC by serving as a competing endogenous RNA of miR-17-5p, mediating the expression of PTEN.
Insights
Long noncoding RNA HOTAIRM1 inhibits gastric cancer progression by targeting miR-17-5p and regulating PTEN expression, suppressing the PI3K/AKT pathway. This finding offers a potential therapeutic strategy for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) is a significant global health concern with complex molecular underpinnings.
- Identifying key regulatory molecules like long noncoding RNAs (lncRNAs) is crucial for understanding GC pathogenesis and developing targeted therapies.
Purpose of the Study:
- To identify significantly altered lncRNAs, messenger RNAs (mRNAs), and pathways in gastric cancer.
- To elucidate the functional role of the lncRNA HOTAIRM1 in GC progression and its molecular mechanisms.
Main Methods:
- Microarray analysis for differential expression of lncRNAs and mRNAs.
- Bioinformatic analyses including coexpression network construction and miRNA target prediction.
- Experimental validation using qRT-PCR, Western blot, dual-luciferase reporter assays, and in vitro/in vivo functional assays (cell viability, migration, apoptosis, xenograft).
Main Results:
- HOTAIRM1 and PTEN were downregulated, while miR-17-5p was upregulated in GC.
- HOTAIRM1 directly targets miR-17-5p, and miR-17-5p targets PTEN, forming a regulatory axis.
- HOTAIRM1 suppressed GC cell proliferation and migration, induced apoptosis, and inhibited tumor growth in vivo by suppressing the PI3K/AKT pathway.
Conclusions:
- LncRNA HOTAIRM1 acts as a tumor suppressor in gastric cancer.
- HOTAIRM1 inhibits GC progression by functioning as a competing endogenous RNA (ceRNA) for miR-17-5p, thereby modulating PTEN expression and suppressing the PI3K/AKT pathway.
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