Clinico-pathological association of delineated miRNAs in uveal melanoma with monosomy 3/Disomy 3 chromosomal aberrations Venkatesan, Nalini, Kanwar, Jagat, Deepa, Perinkulam Ravi, Khetan, Vikas, Crowley, Tamsyn M., Raguraman, Rajeswari, Sugneswari, Ganesan, Rishi, Pukhraj, Natarajan, Viswanathan, Biswas, Jyotirmay and Krishnakumar, Subramanian 2016, Clinico-pathological association of delineated miRNAs in uveal melanoma with monosomy 3/Disomy 3 chromosomal aberrations, PLoS one, vol. 11, no. 1, Article number : e0146128, pp. 1-14, doi: 10.1371/journal.pone.0146128. Attached Files Name Description MIMEType Size Downloads kanwar-clinicopathological-2016.pdf Published version application/pdf 2.02MB 3 Title Clinico-pathological association of delineated miRNAs in uveal melanoma with monosomy 3/Disomy 3 chromosomal aberrations Author(s) Venkatesan, Nalini Kanwar, Jagat Deepa, Perinkulam Ravi Khetan, Vikas Crowley, Tamsyn M. Raguraman, Rajeswari Sugneswari, Ganesan Rishi, Pukhraj Natarajan, Viswanathan Biswas, Jyotirmay Krishnakumar, Subramanian Journal name PLoS one Volume number 11 Issue number 1 Season Article number : e0146128 Start page 1 End page 14 Total pages 14 Publisher PLoS Place of publication San Francisco, Calif. Publication date 2016 ISSN 1932-6203 Summary PURPOSE: To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM) tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort. METHODS: Based on chromosomal 3 aberration, UM (n = 86) were grouped into monosomy 3 (M3; n = 51) and disomy 3 (D3; n = 35) by chromogenic in-situ hybridisation (CISH). The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE) UM samples (n = 6) using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86) and mRNAs were validated in frozen UM (n = 10) by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52). RESULTS: Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0). Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134) were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated. CONCLUSION: UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness. Language eng DOI 10.1371/journal.pone.0146128 Field of Research 119999 Medical and Health Sciences not elsewhere classified Socio Economic Objective 929999 Health not elsewhere classified HERDC Research category C1 Refereed article in a scholarly journal ERA Research output type C Journal article Copyright notice ©2016, The Authors Free to Read? Yes Use Rights Persistent URL http://hdl.handle.net/10536/DRO/DU:30082606 Document type: Journal Article Collections: School of Medicine Open Access Collection Related Links Link Description Connect to Elements publication management system Go to link with your DU access privileges   Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Thu, 07 Apr 2016, 14:26:52 EST Fri, 08 Apr 2016, 05:01:19 EST Fri, 08 Apr 2016, 06:09:50 EST Mon, 26 Sep 2016, 13:17:08 EST Mon, 26 Sep 2016, 13:23:00 EST Mon, 26 Sep 2016, 13:24:05 EST Thu, 20 Oct 2016, 10:15:43 EST Filtered Full Citation counts:   Cited 4 times in TR Web of Science Cited 5 times in Scopus Search Google Scholar Access Statistics: 72 Abstract Views, 4 File Downloads  -  Detailed Statistics Created: Thu, 07 Apr 2016, 14:26:52 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.