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Here, we attempt to comprehensively understand the interactions between long noncoding RNAs (lncRNAs), mRNAs and micro-RNAs (miRNAs) to determine their role in smooth muscle hyperplasia. Differential expression of lncRNAs, mRNAs and miRNAs were obtained by microarray and small-RNA sequencing from HPASMCs treated with and without cocaine and\/or HIV-Tat. LncRNA to mRNA associations were conjectured by analyzing their genomic proximity and by interrogating their association to vascular diseases and cancer co-expression patterns reported in the relevant databases. Neuro-active ligand receptor signaling, Ras signaling and PI3-Akt pathway were among the top pathways enriched in either differentially expressed mRNAs or mRNAs associated to lncRNAs. HPASMC with combined exposure to cocaine and Tat (C\u2009+\u2009T) vs control identified the following top lncRNA-mRNA pairs, ENST00000495536-HOXB13, T216482-CBL, ENST00000602736-GDF7, and, TCONS_00020413-RND1. Many of the down-regulated miRNAs in the HPASMCs treated with C\u2009+\u2009T were found to be anti-proliferative and targets of up-regulated lncRNAs targeting up-regulated mRNAs, including down-regulation of miR-185, -491 and up-regulation of corresponding ENST00000585387. Specific knock down of the selected lncRNAs highlighted the importance of non-coding RNAs in smooth muscle hyperplasia.<\/jats:p>","DOI":"10.1038\/s41598-019-46981-4","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T10:04:13Z","timestamp":1563530653000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Analysis of lncRNA-miRNA-mRNA Interactions in Hyper-proliferative Human Pulmonary Arterial Smooth Muscle Cells"],"prefix":"10.1038","volume":"9","author":[{"given":"Mahendran","family":"Chinnappan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumedha","family":"Gunewardena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakar","family":"Chalise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navneet K.","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"46981_CR1","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1378\/chest.118.4.1133","volume":"118","author":"NJ Mehta","year":"2000","unstructured":"Mehta, N. 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