TY - JOUR
T1 - A novel lncRNA derived from an ultraconserved region
T2 - lnc-uc.147, a potential biomarker in luminal A breast cancer
AU - Pereira Zambalde, Erika
AU - Bayraktar, Recep
AU - Schultz Jucoski, Tayana
AU - Ivan, Cristina
AU - Rodrigues, Ana Carolina
AU - Mathias, Carolina
AU - knutsen, Erik
AU - Silveira de Lima, Rubens
AU - Fiori Gradia, Daniela
AU - de Souza Fonseca Ribeiro, Enilze Maria
AU - Hannash, Samir
AU - Adrian Calin, George
AU - Carvalhode Oliveira, Jaqueline
N1 - Funding Information:
G.A.C and MD Anderson Cancer Center for receiving E.P.Z to develop part of the research. Hospital Nossa Senhora das Graças and patients to disponibility the samples. CAPES, Fundação Araucária, and CNPq to funding. The MD Anderson Cancer Center Proteomics and Metabolomics Facility core for the mass spectrometry analysis.
Funding Information:
This work was supported by the CNPq and CAPES [001 and CAPES/PRINT grant number 88887.194815/2018-00]. G.A.C and MD Anderson Cancer Center for receiving E.P.Z to develop part of the research. Hospital Nossa Senhora das Gra?as and patients to disponibility the samples. CAPES, Funda??o Arauc?ria, and CNPq to funding. The MD Anderson Cancer Center Proteomics and Metabolomics Facility core for the mass spectrometry analysis.
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - The human genome contains 481 ultraconserved regions (UCRs), which are genomic stretches of over 200 base pairs conserved among human, rat, and mouse. The majority of these regions are transcriptionally active (T-UCRs), and several have been found to be differentially expressed in tumours. Some T-UCRs have been functionally characterized, but of those few have been associated to breast cancer (BC). Using TCGA data, we found 302 T-UCRs related to clinical features in BC: 43% were associated with molecular subtypes, 36% with oestrogen-receptor positivity, 17% with HER2 expression, 12% with stage, and 10% with overall survival. The expression levels of 12 T-UCRs were further analysed in a cohort of 82 Brazilian BC patients using RT-qPCR. We found that uc.147 is high expressed in luminal A and B patients. For luminal A, a subtype usually associated with better prognosis, high uc.147 expression was associated with a poor prognosis and suggested as an independent prognostic factor. The lncRNA from uc.147 (lnc-uc.147) is located in the nucleus. Northern blotting results show that uc.147 is a 2,8 kb monoexonic trancript, and its sequence was confirmed by RACE. The silencing of uc.147 increases apoptosis, arrests cell cycle, and reduces cell viability and colony formation in BC cell lines. Additionally, we identifed 19 proteins that interact with lnc-uc.147 through mass spectrometry and demonstrated a high correlation of lnc-uc.147 with the neighbour gene expression and miR-18 and miR-190b. This is the first study to analyse the expression of all T-UCRs in BC and to functionally assess the lnc-uc.147.
AB - The human genome contains 481 ultraconserved regions (UCRs), which are genomic stretches of over 200 base pairs conserved among human, rat, and mouse. The majority of these regions are transcriptionally active (T-UCRs), and several have been found to be differentially expressed in tumours. Some T-UCRs have been functionally characterized, but of those few have been associated to breast cancer (BC). Using TCGA data, we found 302 T-UCRs related to clinical features in BC: 43% were associated with molecular subtypes, 36% with oestrogen-receptor positivity, 17% with HER2 expression, 12% with stage, and 10% with overall survival. The expression levels of 12 T-UCRs were further analysed in a cohort of 82 Brazilian BC patients using RT-qPCR. We found that uc.147 is high expressed in luminal A and B patients. For luminal A, a subtype usually associated with better prognosis, high uc.147 expression was associated with a poor prognosis and suggested as an independent prognostic factor. The lncRNA from uc.147 (lnc-uc.147) is located in the nucleus. Northern blotting results show that uc.147 is a 2,8 kb monoexonic trancript, and its sequence was confirmed by RACE. The silencing of uc.147 increases apoptosis, arrests cell cycle, and reduces cell viability and colony formation in BC cell lines. Additionally, we identifed 19 proteins that interact with lnc-uc.147 through mass spectrometry and demonstrated a high correlation of lnc-uc.147 with the neighbour gene expression and miR-18 and miR-190b. This is the first study to analyse the expression of all T-UCRs in BC and to functionally assess the lnc-uc.147.
KW - T-UCRs
KW - breast cancer
KW - lncRNAs
KW - tumorigenesis
KW - uc.147
KW - ultraconserved region
UR - http://www.scopus.com/inward/record.url?scp=85112569871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85112569871&partnerID=8YFLogxK
U2 - 10.1080/15476286.2021.1952757
DO - 10.1080/15476286.2021.1952757
M3 - Article
C2 - 34387142
AN - SCOPUS:85112569871
SN - 1547-6286
VL - 18
SP - 416
EP - 429
JO - RNA Biology
JF - RNA Biology
IS - S1
ER -