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

Arunagiri Kuha, D. M. R.; Patel, K.; Korivi Jyothi, S.; Balaiah, M.; Sundersingh, S.; Velusami, S.; Thangarajan, R.; Pandey, A.; Chatterjee, A.; Gowda, H.; Mani, S.

doi:10.1101/543397

bioRxiv · 10.1101/543397

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

Arunagiri Kuha, D. M. R.·Patel, K.·Korivi Jyothi, S.·Balaiah, M.·Sundersingh, S.·Velusami, S.·Thangarajan, R.·Pandey, A.·Chatterjee, A.·Gowda, H.·Mani, S.

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Abstract

Breast cancer is a common malignancy among women with the highest incidence rate worldwide. Dysregulation of long non-coding RNAs occurring in the preliminary stages of breast carcinogenesis is poorly understood. In this study, RNA sequencing was done to identify long non-coding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was done in 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 done 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-AS)1. We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and 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.

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Arunagiri Kuha, D. M. R., Patel, K., Korivi Jyothi, S., Balaiah, M., Sundersingh, S., Velusami, S., Thangarajan, R., Pandey, A., Chatterjee, A., Gowda, H., Mani, S.. 2019-02-15. Identification of lncRNAs associated with early stage breast cancer and their prognostic implications. https://doi.org/10.1101/543397

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