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Published on: July 30, 2018
Lnc-SNHG1 Activates the TGFBR2/SMAD3 and RAB11A/Wnt/β-Catenin Pathway by Sponging MiR-302/372/373/520 in Invasive
Heyuan Wang1,2, Guixia Wang1, Yufei Gao3
1Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China.
Background/Aims:
Long noncoding RNAs (lncRNAs) are critical regulators in various diseases including human cancer and could function as competing endogenous RNAs (ceRNAs) to regulate microRNAs (miRNAs).
Methods:
Quantitative real-time PCR (qRT-PCR) was used to analyze the expression of lnc-SNHG1 and miR-302/372/373/520 in pituitary tumor tissues and cell lines. Cell proliferation was investigated using MTT and cell count assays. The mechanisms by which lnc-SNHG1 affects pituitary tumor progression were investigated using Western blot assays, transwell migration assays, immunohistochemistry, immunofluorescence, luciferase reporter assays, tumor xenografts, and flow cytometry Results: We found that lnc-SNHG1 was overexpressed in invasive pituitary tumor tissues and cell lines. Ectopic expression of lnc-SNHG1 promoted cell proliferation, migration, and invasion, as well as the epithelial-mesenchymal transition (EMT), by affecting the cell cycle and cell apoptosis in vitro and tumor growth in vivo. Further study indicated that overexpression of lnc-SNHG1 markedly inhibited the expression of miR-302/372/373/520 (miRNA-pool) which is down-regulated in invasive pituitary tumor cells. Moreover, overexpression of lnc-SNHG1 significantly promoted the expression of TGFBR2 and RAB11A, the direct targets of miR-302/372/373/520. Finally, lnc-SNHG1 activates the TGFBR2/SMAD3 and RAB11A/Wnt/β-catenin pathways in pituitary tumor cells via sponging miR-302/372/373/520.
Conclusions:
Our data suggest that lnc-SNHG1 promotes the progression of pituitary tumors and is a potential therapeutic target for invasive pituitary tumor.
Insights
Long noncoding RNA SNHG1 promotes pituitary tumor growth by inhibiting miR-302/372/373/520. This lncRNA acts as a therapeutic target for invasive pituitary tumors.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are key regulators in diseases like cancer.
- lncRNAs can act as competing endogenous RNAs (ceRNAs) to modulate microRNA (miRNA) activity.
- Pituitary tumors are complex neoplasms where regulatory mechanisms are still being elucidated.
Purpose of the Study:
- To investigate the role of lnc-SNHG1 in pituitary tumor progression.
- To explore the molecular mechanisms underlying lnc-SNHG1's function in pituitary tumors.
- To assess lnc-SNHG1 as a potential therapeutic target.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for gene expression analysis.
- Cellular assays (MTT, cell count, transwell, flow cytometry) for proliferation, migration, invasion, and apoptosis.
- Molecular analyses including Western blot, immunofluorescence, and luciferase reporter assays.
- In vivo tumor xenograft models to assess tumor growth.
Main Results:
- lnc-SNHG1 is overexpressed in invasive pituitary tumors and promotes proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- lnc-SNHG1 overexpression inhibits miR-302/372/373/520 and upregulates target genes TGFBR2 and RAB11A.
- lnc-SNHG1 activates TGFBR2/SMAD3 and RAB11A/Wnt/β-catenin pathways via miRNA sponging.
Conclusions:
- lnc-SNHG1 significantly promotes pituitary tumor progression.
- lnc-SNHG1 acts as a ceRNA by sponging miR-302/372/373/520, thereby activating oncogenic pathways.
- lnc-SNHG1 represents a promising therapeutic target for invasive pituitary tumors.
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