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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.

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Title Clinico-pathological association of delineated miRNAs in uveal melanoma with monosomy 3/Disomy 3 chromosomal aberrations
Author(s) Venkatesan, Nalini
Kanwar, JagatORCID iD for Kanwar, Jagat orcid.org/0000-0003-3728-9568
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 Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30082606

Document type: Journal Article
Collections: School of Medicine
Open Access Collection
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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.