QIMR Berghofer

Identification of lncRNAs associated with early stage breast cancer and their prognostic implications.


Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long non-coding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long non-coding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was performed on 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 performed 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-AS1). We evaluated the prognostic significance of DElncRNAs based on TCGA datasets, and report that 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.

Authors Deva Magendhra Rao, Arunagiri Kuha; Patel, Krishna; Korivi Jyothi, Sunitha; Meenakumari, Balaiah; Sundersingh, Shirley; Velusami, Sridevi; Rajkumar, Thangarajan; Pandey, Akhilesh; Chatterjee, Aditi; Gowda, Harsha; Mani, Samson
Pages 1342-1355
Volume 13
Date 1/04/2019
Grant ID BT/PR8152/AGR/36/739/2013
Funding Body Department of Biotechnology, Govt. of India
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1002/1878-0261.12489