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Published on: March 30, 2019
MicroRNA‑143 targets CD44 to inhibit breast cancer progression and stem cell-like properties
Zhuangqing Yang1, Dedian Chen1, Jianyun Nie1
1Department of Mammary Glands, The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, Yunnan 650118, P.R. China.
Abstract:
CD44 is closely linked to breast cancer progression; however, the regulatory functions of microRNAs (miRs) in breast cancer have yet to be fully elucidated. In order to investigate the regulation of CD44 by miRs in breast cancer, the present study isolated CD44+ and CD44- breast cancer cells by flow cytometry, revealing that CD44+ cells were enriched in transplanted compared with those in primary breast cancers, and that their proliferation and stem-cell sphere formation ability were enhanced. A miRNA array assay indicated that miR-143 expression in CD44+ breast cancer cells was lower than that in CD44- cells. Furthermore, miR-143 was decreased in breast cancer tissues and cell lines compared with that in normal tissues and cells. Restoration of miR-143 expression in CD44+ breast cancer cells inhibited their proliferation and sphere formation. A luciferase reporter assay demonstrated that miR-143 directly tartgeted the 3'-untranslated region of CD44. In addition, miR-143 inhibited metastasis-associated features in breast cancer and reduced tumor growth in a mouse model of breast cancer. In conclusion, the results of the present study demonstrated that miR-143 inhibited the progression and stem-cell properties of breast cancer cells by targeting CD44.
Insights
MicroRNA-143 (miR-143) suppresses breast cancer progression by targeting CD44. Lower miR-143 levels correlate with increased cancer cell proliferation and stem-like properties, highlighting its role as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- CD44 is implicated in breast cancer progression.
- The role of microRNAs (miRs) in regulating CD44 in breast cancer requires further investigation.
Purpose of the Study:
- To investigate the regulatory function of miRs, specifically miR-143, on CD44 in breast cancer.
- To determine the impact of miR-143 on breast cancer cell proliferation, stemness, and metastasis.
Main Methods:
- Isolation of CD44+ and CD44- breast cancer cells via flow cytometry.
- miRNA array assay to compare miR-143 expression levels.
- Luciferase reporter assay to confirm direct targeting of CD44 by miR-143.
- In vivo studies using a mouse model of breast cancer.
Main Results:
- CD44+ breast cancer cells exhibited enhanced proliferation and stem-cell sphere formation.
- miR-143 expression was significantly lower in CD44+ cells, breast cancer tissues, and cell lines compared to normal counterparts.
- Restoring miR-143 inhibited proliferation, sphere formation, and metastasis-associated features.
- miR-143 directly targets the 3'-untranslated region of CD44.
- miR-143 reduced tumor growth in a mouse model.
Conclusions:
- miR-143 acts as a tumor suppressor in breast cancer by directly targeting CD44.
- miR-143 inhibits breast cancer progression, stem-cell properties, and metastasis.
- Therapeutic strategies targeting miR-143 may hold potential for breast cancer treatment.
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