title: Unraveling novel TF-miRNA regulatory crosstalk in metastasis of Soft Tissue Sarcoma.
abstract: Cancer metastasis is a disease of extreme clinical relevance, as it is responsible for more than 90% of cancer-associated mortality. The molecular mechanism and critical regulators involved in this complex multi-stage process of metastasis is poorly deciphered in soft tissue sarcomas (STS), a heterogeneous group of rare tumors with high metastatic potential. Therefore, we aimed at identifying miRNA and transcription factor (TF) regulatory networks and paths in STS metastasis. We integrated mRNA and miRNA expression profiles with curated regulations (TF→gene, TF→miRNA, miRNA→gene) from different databases and constructed a potentially active regulatory sub-network in STS metastasis. From functional and topological analysis, we found nine novel regulators of Notch signaling sub-network which are conjectured to play critical role in metastasis of STS. This illustrated that the sub-network is promising for identification of critical regulators. Further analysis deploying our developed tool 'RiNAcyc' and computing coverage ratio of known STS associated genes and miRNAs identified a 15 node active path. This potential path highlights the crucial role of BMP2, hsa-miR-24, AP2 and MYC as the up-stream regulators of the path and hsa-miR-215 and TYMS as potential indicator of chemotherapeutic benefit in STS metastasis.
authors.affiliation: RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Devyani
authors.initials: D
authors.lastname: Samantarrai
authors.affiliation: RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Sahu
authors.affiliation: RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Roy
authors.affiliation: RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Bedanta Ballav
authors.initials: BB
authors.lastname: Mohanty
authors.affiliation: RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Singh
authors.affiliation: RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Chandra
authors.initials: C
authors.lastname: Bhushan
authors.affiliation: RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Bibekanand
authors.initials: B
authors.lastname: Mallick
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors