S Pranavkrishna1, G Sanjeev1, R L Akshaya1, M Rohini1, N Selvamurugan2. 1. Department of Biotechnology, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 103, Tamil Nadu, India. 2. Department of Biotechnology, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 103, Tamil Nadu, India. Electronic address: selvamun@srmist.edu.in.
Abstract
BACKGROUND: Transforming growth factor-beta1 (TGF-β1) acts as a most effective growth inhibitor for normal epithelial cells. Loss of this anti-proliferative factor in breast tissues favors invasion and development of osteolytic metastases, aided by a master transcription factor, runt-related transcription factor 2 (Runx2). Several reports identified Runx2 regulation with the help of non-coding RNAs such as microRNAs (miRNAs) under physiological and pathological conditions. METHODS: Using bioinformatics tools such as miRDB, STarMir, Venny, TarBase, a unique list of miRNAs that putatively target the 3' UTR Runx2 was identified. Further, the expression patterns of those miRNAs at the precursor and mature levels were studied by RT-qPCR analyses. Following this, computational analyses using software like TransmiR and bc-GenExMiner v4.6 were done to speculate the miRNA's other target genes that indirectly regulate Runx2 activity in breast cancer. RESULTS: There were 13 miRNAs that putatively target Runx2 identified using bioinformatics tools. Among these miRNAs, miR-5703 expression was significantly downregulated at both precursor and mature levels upon TGF-β1-treatment in human breast cancer cells. Computational analyses speculated an indirect targeting of Runx2 by miR-5703 by influencing multiple Runx2 regulatory signaling pathways including Jak/Stat, MAPK, Wnt/β-Catenin, Notch, BMP, and PKA pathways. Furthermore, a correlation of the expression profiles of the speculated genes and Runx2 with miR-5703 was depicted in triple-negative breast cancer patients. CONCLUSION: Identification of miR-5703 and its network for Runx2 regulation directly or indirectly in breast cancer cells could significantly advance our understanding of breast cancer-mediated bone metastasis. In addition, it would potentially pave the way for miRNAs to be used as biomarkers and therapeutic agents in cancer research.
BACKGROUND: Transforming growth factor-beta1 (TGF-β1) acts as a most effective growth inhibitor for normal epithelial cells. Loss of this anti-proliferative factor in breast tissues favors invasion and development of osteolytic metastases, aided by a master transcription factor, runt-related transcription factor 2 (Runx2). Several reports identified Runx2 regulation with the help of non-coding RNAs such as microRNAs (miRNAs) under physiological and pathological conditions. METHODS: Using bioinformatics tools such as miRDB, STarMir, Venny, TarBase, a unique list of miRNAs that putatively target the 3' UTR Runx2 was identified. Further, the expression patterns of those miRNAs at the precursor and mature levels were studied by RT-qPCR analyses. Following this, computational analyses using software like TransmiR and bc-GenExMiner v4.6 were done to speculate the miRNA's other target genes that indirectly regulate Runx2 activity in breast cancer. RESULTS: There were 13 miRNAs that putatively target Runx2 identified using bioinformatics tools. Among these miRNAs, miR-5703 expression was significantly downregulated at both precursor and mature levels upon TGF-β1-treatment in human breast cancer cells. Computational analyses speculated an indirect targeting of Runx2 by miR-5703 by influencing multiple Runx2 regulatory signaling pathways including Jak/Stat, MAPK, Wnt/β-Catenin, Notch, BMP, and PKA pathways. Furthermore, a correlation of the expression profiles of the speculated genes and Runx2 with miR-5703 was depicted in triple-negative breast cancer patients. CONCLUSION: Identification of miR-5703 and its network for Runx2 regulation directly or indirectly in breast cancer cells could significantly advance our understanding of breast cancer-mediated bone metastasis. In addition, it would potentially pave the way for miRNAs to be used as biomarkers and therapeutic agents in cancer research.