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Updated: Mar 14, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-34c Suppresses Breast Cancer Migration and Invasion by Targeting GIT1
Wei-Yang Tao1, Chun-Yang Wang2, Yong-Hui Sun3
1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China;; Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
Abstract:
Abnormal expression of microRNAs plays important role in tumor metastasis. Migration and invasion of cancer cells accord for the metastasis and deterioration of breast cancer. However, the regulatory role of microRNAs in the invasion and migration of breast cancer cells has not completely understood yet. Here we found that microRNA-34c (miR-34c) was significantly downregulated in metastatic tissue of breast cancer. In vitro study showed that miR-34c negatively regulated GIT1 protein expression by binding to the 3'UTR of GIT1 mRNA. Consistently, GIT1 protein expression was found upregulated significantly in metastatic breast cancer. Moreover, miR-34c overexpression suppressed the expression of GIT1 protein, and this effect was restored by AMO-miR-34c in breast cancer cells. Overexpression of miR-34c suppressed cell migration and invasion in both MCF-7 and MDA-MD-231 breast cancer cells. Furthermore, knockdown of endogenous GIT1 expression reduced the migration and invasion of both two breast cancer cells. Collectively, miR-34c downregulation in breast cancer cells resulted in the upregulation of GIT1, which in turn enhanced the migration and invasion of breast cancer. This study highlights molecular mechanism of migration and invasion of breast cancer cells.
Insights
MicroRNA-34c (miR-34c) downregulation in breast cancer promotes metastasis by increasing GIT1 protein. Restoring miR-34c inhibits cancer cell migration and invasion, revealing a key molecular mechanism.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Aberrant microRNA expression is critical in tumor metastasis.
- Breast cancer metastasis involves complex cell migration and invasion processes.
- The precise role of microRNAs in regulating breast cancer cell invasion remains unclear.
Purpose of the Study:
- To investigate the function of microRNA-34c (miR-34c) in breast cancer cell migration and invasion.
- To elucidate the molecular mechanism underlying miR-34c's role in breast cancer metastasis.
Main Methods:
- Quantification of miR-34c and GIT1 protein expression in metastatic breast cancer tissues.
- In vitro studies involving miR-34c mimic and inhibitor (AMO-miR-34c) transfection in breast cancer cell lines (MCF-7, MDA-MD-231).
- Analysis of GIT1 mRNA and protein levels following miR-34c manipulation.
- Assessment of cell migration and invasion assays after modulating miR-34c and GIT1 expression.
Main Results:
- miR-34c was significantly downregulated in metastatic breast cancer tissues.
- miR-34c directly targeted the 3' untranslated region (3'UTR) of GIT1 mRNA, leading to reduced GIT1 protein expression.
- Overexpression of miR-34c suppressed breast cancer cell migration and invasion, while GIT1 knockdown produced similar effects.
- Conversely, GIT1 protein was upregulated in metastatic breast cancer, correlating with decreased miR-34c levels.
Conclusions:
- Downregulation of miR-34c in breast cancer contributes to metastasis by upregulating GIT1.
- The miR-34c/GIT1 axis represents a novel molecular mechanism driving breast cancer cell migration and invasion.
- Targeting this pathway may offer therapeutic strategies for inhibiting breast cancer metastasis.
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