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Let-7a inhibits growth and migration of breast cancer cells by targeting HMGA1
Kui Liu1, Chunfu Zhang2, Tao Li1
1School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
Abstract:
Let-7 is one of the earliest discovered microRNAs (miRNAs) and has been reported to regulate self renewal and tumorigenicity of breast cancer cells. Let-7a is a member of this family and its function has not been fully characterized in breast cancer. First, total RNAs of breast cancer cells (MDA-MB-231, MCF-7), breast cancer tissues and corresponding adjacent normal tissues were extracted and used to detect let-7a expression by qRT-PCR. Secondly, the effects of let-7a on proliferation, colony formation, migration and invasion of breast cancer cells were assessed by in vitro cell culture experiments. Finally, western blotting was performed to demonstrate how let-7a regulated HMGA1 expression. We found that let-7a expression was significantly lower in breast cancer cells and breast cancer tissues compared to corresponding adjacent normal tissues. Cell proliferation, colony formation, migration and invasion were decreased after overexpression of let-7a in breast cancer cells and vice versa. Furthermore, we identified the high mobility group A1 (HMGA1) as a potential target gene of let-7a. Protein expression of the target gene was significantly downregulated in let-7a mimic transfected breast cancer cells and significantly upregulated in let-7a inhibitor transfected breast cancer cells. Our data suggest that let-7a plays an important role as a tumor suppressor gene by targeting HMGA1, which may open novel perspectives for clinical treatments against breast cancer.
Insights
Let-7a, a microRNA, acts as a tumor suppressor in breast cancer by inhibiting cell growth and spread. Its reduced expression in tumors suggests a potential therapeutic target for breast cancer treatment.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Let-7 microRNAs (miRNAs) are known regulators of breast cancer cell self-renewal and tumorigenicity.
- The specific role of let-7a in breast cancer progression remains incompletely understood.
- Understanding let-7a's function is crucial for developing novel breast cancer therapies.
Purpose of the Study:
- To investigate the expression levels of let-7a in breast cancer.
- To elucidate the functional impact of let-7a on breast cancer cell behavior.
- To identify target genes regulated by let-7a in breast cancer.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure let-7a expression in cancer cells and tissues.
- In vitro cell culture assays to assess proliferation, colony formation, migration, and invasion.
- Western blotting to analyze the expression of potential target genes, specifically High Mobility Group A1 (HMGA1).
Main Results:
- Let-7a expression was significantly downregulated in breast cancer cells and tissues compared to normal controls.
- Overexpression of let-7a suppressed breast cancer cell proliferation, colony formation, migration, and invasion.
- HMGA1 was identified as a direct target of let-7a, with its protein expression inversely correlated to let-7a levels.
Conclusions:
- Let-7a functions as a tumor suppressor in breast cancer.
- The tumor-suppressive role of let-7a is mediated, at least in part, by targeting HMGA1.
- Targeting let-7a or its downstream effectors may offer new therapeutic strategies for breast cancer.
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