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Let-7b inhibits cell proliferation, migration, and invasion through targeting Cthrc1 in gastric cancer
Junbo Yu1, Jin Feng, Xiaofei Zhi
1Department of General Surgery, the Affiliated Hospital of Nantong University, Nantong, China.
Abstract:
Dysregulation of specific microRNAs (miRNAs) is found to play a vital role in carcinogenesis and progression of gastric cancer (GC). In the present study, we investigated the expression profiles of miRNAs in gastric cancer. Let-7b was found downregulated remarkably in gastric cancer tissues and was correlated with Helicobacter pylori infection, tumor stage, and lymphatic metastasis. Ectopic expression of let-7b suppressed the growth, migration, invasion, and tumorigenicity of GC cells, whereas let-7b knockdown promoted these phenotypes. Bioinformatic analysis predicted collagen triple helix repeat containing 1 (Cthrc1) as a direct target of let-7b. Luciferase assay showed that let-7b repressed the activity of Cthrc1 through binding its 3'UTR. Western blotting also confirmed that the protein levels of Cthrc1 were decreased by let-7b. Cthrc1 was significantly upregulated and reversely correlated with let-7b levels in GC. Co-expression of let-7b and Cthrc1 without its 3'UTR could rescue cell growth, migration, and invasion inhibited by let-7b. These results suggest that let-7b may directly target Cthrc1 and function as a tumor suppressor gene in GC.
Insights
MicroRNA let-7b is downregulated in gastric cancer (GC) and acts as a tumor suppressor. It targets Cthrc1, inhibiting GC cell growth, migration, and invasion, suggesting therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are crucial in cancer development.
- Gastric cancer (GC) progression involves miRNA dysregulation.
- Specific miRNAs impact GC carcinogenesis.
Purpose of the Study:
- Investigate miRNA expression profiles in gastric cancer.
- Determine the role of let-7b in GC.
- Identify let-7b targets and their function in GC.
Main Methods:
- Analysis of miRNA expression in GC tissues.
- Functional assays (cell growth, migration, invasion, tumorigenicity) with let-7b manipulation.
- Bioinformatic prediction and luciferase reporter assays to validate let-7b targets.
- Western blotting to assess protein levels.
- Correlation analysis between let-7b and target gene expression.
Main Results:
- Let-7b was significantly downregulated in GC tissues.
- Let-7b downregulation correlated with Helicobacter pylori infection, tumor stage, and lymphatic metastasis.
- Overexpression of let-7b inhibited GC cell growth, migration, invasion, and tumorigenicity.
- Knockdown of let-7b promoted these aggressive phenotypes.
- Cthrc1 was identified as a direct target of let-7b.
- Let-7b repressed Cthrc1 expression at both mRNA and protein levels.
- Cthrc1 was upregulated in GC and inversely correlated with let-7b levels.
Conclusions:
- Let-7b functions as a tumor suppressor in gastric cancer.
- Let-7b directly targets and represses Cthrc1 expression.
- The let-7b/Cthrc1 axis plays a significant role in GC progression.
- Let-7b represents a potential therapeutic target for gastric cancer.
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