Open AccessIdentification of lnc RNA s associated with early‐stage breast cancer and their prognostic implications
Author(s) -
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
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12489
Subject(s) - breast cancer , biology , rna , carcinogenesis , ductal carcinoma , long non coding rna , cancer research , malignancy , cancer , gene silencing , breast carcinoma , downregulation and upregulation , microbiology and biotechnology , oncology , medicine , genetics , gene
Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNA s 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 DE lnc RNA s. About 20% of the 375 DE lnc RNA s 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 ( ADAMTS 9‐ AS 2, EPB 41L4A‐ AS 1, WDFY 3‐ AS 2, RP 11‐295M3.4, RP 11‐161M6.2, RP 11‐490M8.1, CTB ‐92J24.3, and FAM 83H‐ AS 1). We evaluated the prognostic significance of DE lnc RNA s based on TCGA datasets and report that overexpression of FAM 83H‐ AS 1 was associated with patient poor survival. We confirmed that the downregulation of ADAMTS 9‐ AS 2 in breast cancer was due to promoter hypermethylation through in vitro silencing experiments and pyrosequencing.