MiR-153 regulates metastases of gastric cancer through Snail
1Department of General Surgery, the First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
Abstract:
MicroRNAs (miRNAs) play critical roles in tumorigenesis and cancer metastases of gastric carcinoma (GC). Recently, miR-153 was reported as a tumor suppressor miRNA silenced in GC, whereas the underlying mechanisms are much lacking. Here, we reported that miR-153 levels were significantly decreased and Snail levels were significantly increased in GC specimens, compared to paired adjacent non-tumor gastric tissue. Moreover, the levels of miR-153 and Snail were inversely correlated. Bioinformatics analyses and luciferase reporter assay showed that miR-153 targeted the 3'-untranslated region (3'-UTR) of Snail messenger RNA (mRNA) to inhibit its translation. Overexpression of miR-153 inhibited Snail-mediated cell invasiveness, while depletion of miR-153 increased Snail-mediated cell invasiveness in both Transwell cell migration assay and scratch wound healing assay. Thus, our data suggest that miR-153 suppression in GC promotes Snail-mediated cancer metastases. Re-establishment of miR-153 levels in GC may suppress cancer invasion.
Insights
MicroRNA-153 (miR-153) acts as a tumor suppressor in gastric cancer (GC) by inhibiting Snail. Reduced miR-153 levels promote GC metastasis, suggesting miR-153 restoration could combat cancer invasion.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial regulators in gastric carcinoma (GC) tumorigenesis and metastasis.
- miR-153 is identified as a tumor suppressor miRNA frequently silenced in GC, but the mechanisms remain unclear.
- Gastric carcinoma is a significant global health concern, necessitating research into its underlying molecular mechanisms.
Purpose of the Study:
- To investigate the role of miR-153 in gastric carcinoma progression.
- To elucidate the molecular mechanism by which miR-153 affects gastric cancer metastasis.
- To explore the relationship between miR-153 and Snail in gastric cancer.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to measure miR-153 and Snail levels.
- Bioinformatics analysis to predict miR-153 targets.
- Luciferase reporter assay to validate miR-153 targeting of Snail mRNA.
- Transwell cell migration and scratch wound healing assays to assess cell invasiveness.
Main Results:
- miR-153 levels were significantly decreased, while Snail levels were significantly increased in GC tissues compared to adjacent non-tumor tissues.
- A significant inverse correlation was observed between miR-153 and Snail expression levels.
- miR-153 directly targets the 3'-untranslated region (3'-UTR) of Snail mRNA, inhibiting its translation.
- Overexpression of miR-153 suppressed Snail-mediated cell invasiveness, whereas miR-153 depletion enhanced it.
Conclusions:
- Suppression of miR-153 in gastric carcinoma promotes Snail-mediated cancer metastasis.
- Restoring miR-153 levels holds potential for suppressing gastric cancer invasion and metastasis.
- miR-153 functions as a tumor suppressor by targeting Snail in gastric cancer.
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