A Novel LncRNA Derived from an Ultraconserved Region: Lnc-, a Potential Biomarker in Luminal A Breast Cancer

Overview

Journal RNA Biol

Specialty Molecular Biology

Date 2021 Aug 13

PMID 34387142

Citations 7

Authors

Erika Pereira Zambalde

Recep Bayraktar

Tayana Schultz Jucoski

Cristina Ivan

Ana Carolina Rodrigues

Carolina Mathias

Erik Knutsen

Rubens Silveira DE Lima

Daniela Fiori Gradia

Enilze Maria de Souza Fonseca Ribeiro

Samir Hannash

George Adrian Calin

Jaqueline Carvalhode Oliveira

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Ultra-conserved RNA: a novel biological tool with diagnostic and therapeutic potential.

Wang T, Li F, Lu Z Discov Oncol. 2023; 14(1):41.

PMID: 37036543 PMC: 10086085. DOI: 10.1007/s12672-023-00650-1.

Lnc-uc.147 Is Associated with Disease Stage of Liver, Gastric, and Renal Cancer.

Rodrigues A, Zambalde E, de Lima Bellan D, Silva Trindade E, Ribeiro E, Calin G Biomolecules. 2023; 13(2).

PMID: 36830634 PMC: 9953473. DOI: 10.3390/biom13020265.

Transcribed Ultraconserved Regions: New regulators in cancer signaling and potential biomarkers.

de Oliveira J Genet Mol Biol. 2023; 46(1 Suppl 2):e20220125.

PMID: 36622962 PMC: 9829027. DOI: 10.1590/1678-4685-GMB-2022-0125.

Role of transcribed ultraconserved regions in gastric cancer and therapeutic perspectives.

Gao S, Zhang Z, Wang X, Ma Y, Yin G, Guo X World J Gastroenterol. 2022; 28(25):2900-2909.

PMID: 35978878 PMC: 9280734. DOI: 10.3748/wjg.v28.i25.2900.

Transcribed Ultraconserved Regions in Cancer.

Gibert Jr M, Sarkar A, Chagari B, Roig-Laboy C, Saha S, Bednarek S Cells. 2022; 11(10).

PMID: 35626721 PMC: 9139194. DOI: 10.3390/cells11101684.

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