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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-212 functions as a tumor-suppressor in human non-small cell lung cancer by targeting SOX4
Tingting Tang1, Liting Huan2, Shujuan Zhang2
1Department of Hematology and Oncology, The Affiliated Hospital of Hangzhou Normal University, Gongshu, Hangzhou, Zhejiang 310015, P.R. China.
Abstract:
Increasing evidence has revealed that aberrant expression of miRNAs contributes to non-small cell lung cancer (NSCLC) development and progression. However, the roles and mechanisms of various miRNAs in NSCLC remain to be determined. In the present study, we confirmed that reduced miR-212 expression was present in NSCLC tissues and cell lines. Our clinical analysis revealed that the reduced miR-212 expression was significantly correlated with poor prognostic features including positive lymph node metastasis and advanced tumor-node-metastasis (TNM) stage. Moreover, we demonstrated that miR-212 is a novel independent prognostic marker for predicting 5-year survival of NSCLC patients. The ectopic overexpression of miR-212 inhibited cell migration, invasion and EMT, while downregulated miR-212 reversed the effect. In addition, miR-212 regulated SOX4 by directly binding to its 3'-untranslated region (3'-UTR), leading to suppression of EMT progression. In clinical samples of NSCLC, miR-212 was negatively correlated with SOX4, which was upregulated in NSCLC. Alteration in SOX4 expression reversed the functional effects of miR-212 in regards to migration, invasion and EMT in the NSCLC cells. In conclusion, our data indicated that miR-212 functions as a tumor-suppressor gene by regulating EMT and metastasis of NSCLC by targeting SOX4 signaling, and may represent a novel potential therapeutic target and prognostic marker for NSCLC.
Insights
Reduced miR-212 expression is linked to non-small cell lung cancer (NSCLC) progression and metastasis. Restoring miR-212 inhibits NSCLC cell invasion and EMT by targeting SOX4, suggesting its potential as a therapeutic target.
Area of Science:
- Molecular Oncology
- Cancer Biology
- MicroRNA Therapeutics
Background:
- Aberrant microRNA (miRNA) expression is implicated in non-small cell lung cancer (NSCLC) pathogenesis.
- The specific roles and regulatory mechanisms of many miRNAs in NSCLC remain incompletely understood.
- Understanding miRNA functions is crucial for developing novel diagnostic and therapeutic strategies for NSCLC.
Purpose of the Study:
- To investigate the role and mechanism of miR-212 in non-small cell lung cancer (NSCLC).
- To determine if miR-212 can serve as a prognostic biomarker for NSCLC patients.
- To elucidate the downstream targets and signaling pathways regulated by miR-212 in NSCLC.
Main Methods:
- Quantitative real-time PCR to assess miR-212 expression in NSCLC tissues and cell lines.
- Bioinformatic analysis and luciferase reporter assays to identify miR-212 targets.
- In vitro cell migration, invasion, and epithelial-mesenchymal transition (EMT) assays following miR-212 modulation.
Main Results:
- Downregulated miR-212 expression was observed in NSCLC tissues and correlated with advanced TNM stage and lymph node metastasis.
- Overexpression of miR-212 suppressed NSCLC cell migration, invasion, and EMT, while its downregulation promoted these processes.
- miR-212 directly targets SOX4, inhibiting EMT progression; miR-212 was negatively correlated with SOX4, which was upregulated in NSCLC.
Conclusions:
- miR-212 functions as a tumor suppressor in NSCLC by inhibiting EMT and metastasis through the SOX4 signaling pathway.
- Reduced miR-212 expression is a significant independent prognostic marker for predicting 5-year survival in NSCLC patients.
- miR-212 represents a potential therapeutic target and prognostic biomarker for non-small cell lung cancer.
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