Abstract
BackgroundmiRNAs, endogenous oligonucleotide RNAs, play an important role in mammary gland carcinogenesis and tumor progression. Detection of their expression and investigation of their functions could lead to discovery of novel biomarkers for breast cancer.MethodsIn situ hybridization was used to detect miR-133a expression in formalin-fixed paraffin-embedded breast surgical specimens from 26 benign, 34 pericancerously normal and 90 cancerous tissues. qRT-PCR was performed to assess miR-133a levels in 6 breast cell lines and 10 benign and 18 cancerous fresh breast tissue specimens. Cell viability, migration, and invasion assays were used to determine the role of miR-133a in regulation of breast cancer cell growth, migration, and invasion, respectively. Luciferase assay was performed to assess miR-133a binding to FSCN1 gene.ResultsExpression of miR-133a was reduced from normal through benign to cancerous breast tissues. Expression of miR-133a was also low in breast cancer cell lines. The reduced miR-133a expression was associated with lymph nodes metastasis, high clinical stages, and shorter relapse-free survivals of patients with breast cancer. Furthermore, transfection of miR-133a oligonucleotides slightly inhibited growth but significantly decreased migration and invasion capacity of breast cancer cells, compared with negative controls, whereas knockdown of miR-133a expression induced breast cancer cell migration and invasion. In addition, we identified a putative miR-133a binding site in the 3'-untranslated region (UTR) of Fascin1 (FSCN1) gene using an online bioinformatical tool. We found that miR-133a transfection significantly reduced expression of FSCN1 mRNA and protein. The luciferase reporter assay confirmed that FSCN1 was the direct target gene of miR-133a.ConclusionsmiR-133a expression was lost in breast cancer tissues, loss of which was associated with lymph nodes metastasis, high clinical stages and shorter relapse-free survivals of patients with breast cancer. Functionally, miR-133a can suppress tumor cell invasion and migration and targeted the expression of FSCN1. Future study will verify whether detection of miR-133a expression can served as a novel biomarker for breast cancer progression and patient prognosis.
Highlights
MiRNAs, endogenous oligonucleotide RNAs, play an important role in mammary gland carcinogenesis and tumor progression
We screened expression of different miRNAs in archived formalinfixed and paraffin-embedded breast tissue specimens by in situ hybridization [10,28], we found significant downregulated miR-133a expression in breast cancer compared to benign breast disease and miR-133a downregulation was associated with disease progression
Expression of miR-133a in breast tissue specimens and breast cell lines In this study, we first assessed expression levels of miR133a in 34 normal, 26 benign, and 90 cancerous tissue samples using in situ hybridization
Summary
MiRNAs, endogenous oligonucleotide RNAs, play an important role in mammary gland carcinogenesis and tumor progression Detection of their expression and investigation of their functions could lead to discovery of novel biomarkers for breast cancer. MicroRNAs (miRNAs) are a class of small, non-coding RNAs of 18-24 nucleotides in length and function as negative regulators of gene expression through inhibition of target mRNA translation or degradation of target mRNA [1] Through silence of their targeting mRNAs, miRNAs play key roles in a wide variety of biological processes, including control of embryo development [2], cell growth [3], differentiation [4] and apoptosis [5,6,7]. We assessed the role of miR-133a in breast cancer cell lines and linked miR-133a expression with FSCN1 alteration
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