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

• Published in: Molecular oncology Vol. 13; no. 6; pp. 1342 - 1355
• Main Authors: Deva Magendhra Rao, Arunagiri Kuha, Patel, Krishna, Korivi Jyothiraj, Suneetha, Meenakumari, Balaiah, Sundersingh, Shirley, Sridevi, Velusami, Rajkumar, Thangarajan, Pandey, Akhilesh, Chatterjee, Aditi, Gowda, Harsha, Mani, Samson
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-06-2019; John Wiley and Sons Inc; Wiley
• Subjects: ADAMTS9‐AS2; Antisense RNA; Biomarkers, Tumor - genetics; breast cancer; Breast Neoplasms - genetics; Carcinoma, Ductal; Comparative analysis; Development and progression; FAM83H‐AS1; Female; Gene Expression Regulation, Neoplastic - genetics; Gene Regulatory Networks - genetics; Humans; long noncoding RNAs; ncRNAs; Prognosis; RNA sequencing; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sequence Analysis, RNA; RNA sequencing; breast cancer; FAM83H-AS1; ADAMTS9-AS2; long noncoding RNAs; ncRNAs
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1002/1878-0261.12489

Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated with early‐stage breast cancer. RNA sequencing was performed on six invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, seven ductal carcinoma in situ tissues, and five 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 downregulation of ADAMTS9‐AS2 in breast cancer was due to promoter hypermethylation through in vitro silencing experiments and pyrosequencing.
Whole transcriptome sequencing was performed to identify aberrantly expressed long noncoding RNAs (lncRNAs) in early‐stage breast cancer tissues (invasive ductal carcinoma and ductal carcinoma in situ), paired normal, and apparently normal tissues. Antisense and long intergenic noncoding RNAs were found to be most deregulated among various biotypes. Down regulation of ADAMTS9‐AS2 was due to the promoter hypermethylation in breast cancer cells compared to normal breast cells.