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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
Tumor suppressive microRNA-193b promotes breast cancer progression via targeting DNAJC13 and RAB22A
Zhaoying Yang1, Miao He2, Keren Wang1
1Department of Breast Surgery, China-Japan Union Hospital of Jilin University Changchun, Jilin, China ; Breast Disease Research Institute of Jilin Province Changchun, Jilin, China.
Abstract:
Breast cancer is still a leading cause of cancer deaths in women. Despite improvements in therapeutic approaches in local control, metastatic relapse is almost always incurable, underlining the importance to better understand the biological bases that contribute to disease progression. In this study, we demonstrated that miR-193b was significantly down-regulated in two primary human breast cancer cell lines (MDA-MB-231 and MCF-7). Reconstitution of miR-193b expression resulted in decreasing cell proliferation, clonogenicity, migration and invasion. By using in silico prediction algorithms approach for target identification, we identified DNAJC13 (HPS40) and RAB22A to be direct targets of miR-193b. Concordantly, Re-expression of miR-193b decreased DNAJC13 (HPS40) and RAB22A expression. Luciferase reporter assays confirmed the direct interaction of miR-193b with both DNAJC13 (HPS40) and RAB22A. Our findings have demonstrated that miR-193b as a novel tumor suppressor plays an important role in breast cancer progression, understanding the mechanisms could account for the aggressive behaviour of breast cancer.
Insights
MicroRNA-193b (miR-193b) acts as a tumor suppressor in breast cancer. Restoring miR-193b levels inhibits cancer cell growth, migration, and invasion by targeting DNAJC13 and RAB22A.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer remains a significant cause of mortality in women worldwide.
- Metastatic relapse in breast cancer is often incurable, highlighting the need to understand disease progression mechanisms.
Purpose of the Study:
- To investigate the role of microRNA-193b (miR-193b) in breast cancer progression.
- To identify direct targets of miR-193b involved in breast cancer development.
Main Methods:
- Down-regulation of miR-193b was assessed in human breast cancer cell lines (MDA-MB-231, MCF-7).
- Functional assays (proliferation, clonogenicity, migration, invasion) were performed after miR-193b reconstitution.
- In silico prediction algorithms and luciferase reporter assays were used to identify and confirm direct targets (DNAJC13, RAB22A).
Main Results:
- miR-193b was significantly down-regulated in breast cancer cell lines.
- Restoring miR-193b expression reduced cell proliferation, clonogenicity, migration, and invasion.
- DNAJC13 and RAB22A were validated as direct targets of miR-193b, with their expression decreased upon miR-193b re-expression.
Conclusions:
- miR-193b functions as a novel tumor suppressor in breast cancer.
- The miR-193b/DNAJC13/RAB22A pathway is implicated in regulating breast cancer cell aggressiveness and progression.
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