Identification of lnc RNA s 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: Hoboken John Wiley & Sons, Inc 01-06-2019
• Subjects: Antisense RNA; Breast cancer; Carcinogenesis; Gene expression; Industrial research; Invasiveness; Kinases; Malignancy; Medical prognosis; Phosphorylation; Principal components analysis; R&D; Research & development; Ribonucleic acid; RNA; Scholarships & fellowships; Tumors; United States > US; India
• 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
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.