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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Knockdown of Long Noncoding RNA Small Nucleolar RNA Host Gene 12 Inhibits Cell Growth and Induces Apoptosis by
Xiaoyan Wang1, Guanbin Qi1, Juanjuan Zhang1
1Department of Pneumology, Huaihe Hospital of Henan University , Kaifeng, China .
Abstract:
Small nucleolar RNA host gene 12 (SNHG12) is a novel long noncoding RNA identified to be upregulated and functions as an oncogene in several cancers. However, the function of SNHG12 and its target genes in modulating nonsmall cell lung cancer (NSCLC) development are rarely reported. In the present study, we validated that SNHG12 was overexpressed, while miR-138 was low-expressed, in NSCLC cells compared with normal human lung epithelial cells. SNHG12 harbored the binding site of miR-138 and inversely regulated the expression miR-138. Knockdown of SNHG12 inhibited proliferation and colony-forming ability, induced apoptosis, and increased caspase-3 activity of NSCLC cells, whereas miR-138 downregulation restored these effects. Furthermore, SNHG12 knockdown decreased volumes and weight of xenograft tumors in a NSCLC mouse model. Taken together, these findings suggested that knockdown of SNHG12 suppressed cell growth and induced apoptosis by upregulating miR-138 in NSCLC.
Insights
Small nucleolar RNA host gene 12 (SNHG12) is overexpressed in nonsmall cell lung cancer (NSCLC). Reducing SNHG12 inhibits NSCLC growth and promotes apoptosis by increasing miR-138 levels.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Small nucleolar RNA host gene 12 (SNHG12) is a long noncoding RNA implicated as an oncogene in various cancers.
- The specific role of SNHG12 in nonsmall cell lung cancer (NSCLC) pathogenesis and its molecular targets remain underexplored.
Purpose of the Study:
- To investigate the role of SNHG12 in NSCLC development.
- To elucidate the regulatory relationship between SNHG12 and miR-138 in NSCLC cells.
Main Methods:
- Quantitative real-time PCR to assess SNHG12 and miR-138 expression levels in NSCLC cells and normal lung epithelial cells.
- Western blotting to measure caspase-3 activity.
- Cell proliferation assays, colony formation assays, and apoptosis assays.
- In vivo studies using a NSCLC mouse xenograft model.
Main Results:
- SNHG12 was significantly upregulated, and miR-138 was downregulated in NSCLC cells compared to normal controls.
- SNHG12 directly binds to miR-138, negatively regulating its expression.
- Knockdown of SNHG12 suppressed NSCLC cell proliferation, colony formation, and induced apoptosis, evidenced by increased caspase-3 activity.
- Restoration of miR-138 partially reversed the effects of SNHG12 knockdown.
- In vivo, SNHG12 knockdown significantly reduced tumor volume and weight in the NSCLC mouse model.
Conclusions:
- SNHG12 acts as an oncogene in NSCLC by downregulating miR-138.
- Targeting SNHG12 represents a potential therapeutic strategy for NSCLC by inhibiting tumor growth and inducing apoptosis.
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