Abstract

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
Journal	MOLECULAR ONCOLOGY
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