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miR-103 regulates triple negative breast cancer cells migration and invasion through targeting olfactomedin 4
Bin Xiong1, Xuefeng Lei1, Lei Zhang1
1Surgery Teaching and Research Section, Clinical Medical School, Jining Medical University, NO. 16 Hehua Road, Jining, Shandong 272067, China.
Abstract:
Our previous study showed olfactomedin 4 (OLFM4) suppressed triple-negative breast cancer cells migration, invasion and metastasis-associated protein MMP 9 expression. OLFM4 was identified as a potential target of miR-103 according to microRNA target databases and published studies. The aim of this study is to validate the relationship between miR-103 and OLFM4, and explore the function and clinical significance of miR-103 in triple-negative breast cancer patients. In our results, miR-103 negatively regulated OLFM4 expression by directly targeting its 3'-UTR. OLFM4 was a functional target of miR-103 to regulate triple-negative breast cancer cells migration, invasion and MMP 9 expression. Moreover, miR-103 overexpression was observed in triple-negative breast cancer tissues and cell lines, and associated with lymph node metastasis, distant metastasis and clinical stage. Univariate and multivariate analyses suggested that miR-103 overexpression was a poor independent prognostic factor for triple-negative breast cancer patients. In conclusion, miR-103 acts as an oncogene miRNA to promote triple-negative breast cancer cells migration and invasion through targeting OLFM4.
Insights
MicroRNA-103 (miR-103) promotes triple-negative breast cancer (TNBC) cell migration and invasion by suppressing olfactomedin 4 (OLFM4). Overexpression of miR-103 is linked to advanced TNBC and poorer patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Olfactomedin 4 (OLFM4) previously demonstrated suppression of triple-negative breast cancer (TNBC) cell migration, invasion, and matrix metalloproteinase 9 (MMP 9) expression.
- MicroRNA-103 (miR-103) was computationally identified as a potential regulator of OLFM4.
Purpose of the Study:
- To validate the regulatory relationship between miR-103 and OLFM4.
- To investigate the functional role of miR-103 in TNBC cell behavior.
- To determine the clinical significance of miR-103 in TNBC patients.
Main Methods:
- Dual-luciferase reporter assays to confirm direct targeting of OLFM4 by miR-103.
- Cell migration and invasion assays in TNBC cell lines.
- Quantitative real-time PCR and Western blotting to assess OLFM4 and miR-103 expression.
- Retrospective analysis of TNBC patient tissues and clinical data.
Main Results:
- miR-103 directly targets the 3'-untranslated region (3'-UTR) of OLFM4, leading to its downregulation.
- miR-103 promotes TNBC cell migration and invasion, partly through the regulation of OLFM4 and MMP 9 expression.
- Overexpression of miR-103 was detected in TNBC tissues and cell lines.
- miR-103 overexpression correlated significantly with lymph node metastasis, distant metastasis, and advanced clinical stage in TNBC patients.
Conclusions:
- miR-103 functions as an oncogenic microRNA in triple-negative breast cancer.
- miR-103 promotes TNBC cell migration and invasion by targeting OLFM4.
- miR-103 overexpression serves as a potential independent prognostic biomarker for poor outcomes in TNBC patients.
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