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摘要
Accumulating evidence has revealed that miR-449a expression was downregulated in various human cancers, downregulation of which was associated with cancer development and progression. This study assessed miR-449a expression in different molecular subtypes of breast cancer tissue specimens and explored miR-449a-targeting genes to predict novel gene pathways involved in breast cancer. Paired tissue specimens from 58 breast cancer patients were collected for qRT-PCR analysis of miR-449a expression and gene ontology, KEGG analyses were performed to predict miR-449a-targeting genes and pathways with different web-based tools. The data showed that miR-449a expression was reduced in breast cancer tissue specimens compared to the corresponding adjacent breast tissues (P < 0.05) and miR-449a was significantly down-regulated in all four different molecular subtypes of breast cancer, in particular, in triple negative breast cancer. Level of miR-449a was also lower in the breast cancer cell line MDA-MB-231 than that of MCF-7 cell line. Reduced miR-449a expression was significantly associated with advanced breast cancer TNM staging and lymph node metastasis (P < 0.05). The gene ontology, KEGG pathway and network analytic data showed that miR-449a could regulate genes that are involved in cell proliferation and transcription regulator activity, sequence-specific DNA binding and enzyme binding, cytoskeleton, endocytosis, Notch signaling pathway, p53 signaling pathway, and MAPK signaling pathway. Hub genes (such as SRC, NOTCH1, BCL2, HDAC1, CCND1, and CDK6) may play critical roles in their co-regulatory networks. Collectively, these data suggest that detection of miR-449a expression could serve as a tumor marker in the prediction of breast cancer progression and metastasis. Further investigation of miR-449a and miR-449a-targeting genes and pathways could provide novel strategies for breast cancer patients.
- 出版日期2016
- 单位广西医科大学
