Abstract
Breast cancer is a common malignancy among women with the highest incidence rate worldwide. Dysregulation of long non-coding RNAs occurring in the preliminary stages of breast carcinogenesis is poorly understood. In this study, RNA sequencing was done to identify long non-coding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was done in 6 invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, 7 ductal carcinoma in situ (DCIS) tissues and 5 apparently normal breast tissues. We identified 375 differentially expressed lncRNAs (DElncRNAs) in IDC tissues compared to paired normal tissues. Antisense transcripts (∼58%) were the largest subtype among DElncRNAs. About 20% of the 375 DElncRNAs were supported by typical split readings leveraging their detection confidence. Validation was done in n=52 IDC and paired normal tissue by qRT-PCR for the identified targets (ADAMTS9-AS2, EPB41L4A-AS1, WDFY3-AS2, RP11-295M3.4, RP11-161M6.2, RP11-490M8.1, CTB-92J24.3 and FAM83H-AS)1. We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and overexpression of FAM83H-AS1 was associated with patient poor survival. We confirmed that the down-regulation of ADAMTS9-AS2 in breast cancer was due to promoter hypermethylation through in-vitro silencing experiments and pyrosequencing.
Footnotes
E-mail addresses (Complying to the order of author list) akdmr26newgeneite{at}gmail.com, krishnapatel{at}ibioinformatics.org, sunithazy{at}gmail.com, hemmeena{at}gmail.com, shirleysundersingh{at}hotmail.com, sri04devi{at}yahoo.co.in, drtrajkumar{at}gmail.com, Pandey.Akhilesh{at}mayo.edu, aditi{at}ibioinformatics.org, harsha{at}ibioinformatics.org and samsonn.m{at}gmail.com
- Abbreviations
- DCIS
- ductal carcinoma in situ
- IDC
- invasive ductal carcinoma
- NGS
- Next generation sequencing
- lncRNA
- long non-coding RNAs
- lincRNA
- long intergenic non-coding RNA
- TNBC
- Triple negative breast cancers
- BH
- Bonferroni and Benjamini–Hochberg
- PCA
- Principal component analysis
- PCC
- Pearson’s correlation coefficient
- PCG
- Protein coding genes