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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma
Xiaoying Wang1, Yanli Liu2, Xiaoli Liu3
1Department of Pathology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Abstract:
Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) may contribute to the initiation and progression of cancer. However, the role of miR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which miR-124 exerts its functions are not completely understood. In the present study, we detected miR-124 and SOX9 expression in lung ADC tissues. The results showed that miR-124 was significantly downregulated in the lung ADC tissues compared with that noted in the corresponding non-cancerous lung tissues and the level of SOX9 protein was inversely associated with the expression of miR-124. The study in human lung ADC cell line A549 demonstrated that upregulation of miR-124 could inhibit cell proliferation, migration and invasion. The bioinformatic analysis showed that there was a putative miR-124 binding site in the 3' untranslated region (3'UTR) of SOX9. Using a luciferase reporter assay, we verified that SOX9 is a direct target of miR-124. Furthermore, overexpression of miR-124 repressed SOX9 expression, whereas inhibition of miR-124 increased expression of SOX9 in the A549 cells. Finally, we identified that SOX9 was a functional mediator of miR-124 in A549 cells. Taken together, our results suggest that miR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9 and it may be a promising candidate for miR‑based therapy against lung ADC.
Insights
MicroRNA-124 (miR-124) acts as a tumor suppressor in lung adenocarcinoma (ADC) by inhibiting cancer cell growth and spread. It directly targets SOX9, suggesting potential for miR-124 based therapies in lung ADC treatment.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNA (miRNA) dysregulation is implicated in cancer development.
- The specific role and mechanism of miR-124 in lung adenocarcinoma (ADC) remain unclear.
Purpose of the Study:
- To investigate the function of miR-124 in lung ADC.
- To elucidate the underlying molecular mechanisms involving SOX9.
Main Methods:
- Quantitative analysis of miR-124 and SOX9 expression in lung ADC tissues and cell lines.
- Cell proliferation, migration, and invasion assays.
- Bioinformatic analysis, luciferase reporter assays, and Western blotting to confirm SOX9 as a direct target of miR-124.
Main Results:
- miR-124 was significantly downregulated in lung ADC tissues.
- miR-124 overexpression inhibited proliferation, migration, and invasion of A549 lung ADC cells.
- SOX9 was identified as a direct target of miR-124, with its expression inversely correlated to miR-124 levels.
Conclusions:
- miR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9.
- miR-124 may serve as a potential therapeutic target for lung ADC treatment.
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