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

Arunagiri Kuha Deva Magendhra Rao, Krishna Patel, Suneetha Korivi Jyothiraj, Balaiah Meenakumari, Shirley Sundersingh, Velusami Sridevi, Thangarajan Rajkumar, Akhilesh Pandey, Aditi Chatterjee, Harsha Gowda, Samson Mani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1342-1355
Number of pages14
JournalMolecular oncology
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2019
Externally publishedYes

Keywords

  • ADAMTS9-AS2
  • breast cancer
  • FAM83H-AS1
  • long noncoding RNAs
  • ncRNAs
  • RNA sequencing

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications'. Together they form a unique fingerprint.

  • Cite this

    Deva Magendhra Rao, A. K., Patel, K., Korivi Jyothiraj, S., Meenakumari, B., Sundersingh, S., Sridevi, V., Rajkumar, T., Pandey, A., Chatterjee, A., Gowda, H., & Mani, S. (2019). Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications. Molecular oncology, 13(6), 1342-1355. https://doi.org/10.1002/1878-0261.12489