Abstract
Objectives: Breast cancer has been the second most prevalent and fatal malignancy due to its frequent metastasis to other organs. We aim to study the effects of a key miRNA-mRNA signaling in breast cancer.Results: CNN1 was identified as the key gene in breast cancer by the bioinformatics analysis, and the downregulation of CNN1 in breast cancer tissues and cell lines was observed. Upregulating CNN1 inhibited cell survival, migration, invasion, and adhesion, but enhanced cell apoptosis. miR-106b-5p not only bound to CNN1 mRNA 3’UTR, but also promoted lung metastasis in vivo. Besides, the miR-106b-5p mimic enhanced breast cancer canceration by targeting CNN1 and activating Rho/ROCK1 signaling pathway.Conclusion: Overall, our results proved that miR-106b-5p promoted the metastasis of breast cancer by suppressing CNN1 and activating Rho/ROCK1 pathway.Methods: Bioinformatics analysis was performed to select the key gene in breast cancer. The overexpression and knockdown of Calponin 1 (CNN1) in breast cancer cell lines were performed to conduct cell viability, migrating, invasion, proliferation, adhesion, and apoptosis experiments. To identify the role of miR-106b-5p and Rho/ROCK1 in CNN1-induced breast cancer, a dual-luciferase assay, tumor lung metastasis assay, transcript half-life assay, and Rho/ROCK1 inhibition assay were performed.
Highlights
Breast cancer (BRCA) has been the second most prevalent and dreadful malignancy that primarily occurs among females, leading to over two million cases and 626,679 deaths in 2019 based on the TCGA cancer statistics
ACOT7, STAT1, TYMP, and VOPP1 were significantly increased in invasive breast carcinoma, while the gene expressions of ACTG2, Calponin 1 (CNN1), CDC14B, NFIB, RCN1, and TRIM2 were dramatically downregulated in BRCA
Breast Cancer Gene-Expression Miner v4.4 was used to further analyze the expression of CNN1 and STAT1 in different subtypes of breast cancer, indicating that the expression of CNN1 and STAT1 is markedly different in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), micropapillary, mucinous, and triple negative breast cancer (TNBC) (Figure 1E)
Summary
Breast cancer (BRCA) has been the second most prevalent and dreadful malignancy that primarily occurs among females, leading to over two million cases and 626,679 deaths in 2019 based on the TCGA cancer statistics. The local invasion and metastasis to distant organs like lung, liver, and brain were responsible for breast cancer-related deaths [1,2,3]. Exploring the molecular mechanism underlying BRCA development the invasion and metastasis is critical to diagnose and remedy breast cancer. MiRNAs are broadly expressed in all sorts of normal and diseased tissues. In the past few decades, accumulating studies have proved that the epigenetic abnormities including aberrant miRNA expressions are associated with the development of breast cancer [4]. Accumulating studies have proved the potential of miRNAs in both the diagnosis and therapeutics of breast cancer [7,8,9]. Li et al reported that miR-29c participated in suppressing the progression of breast cancer by targeting www.aging-us.com
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