Transcribed Ultraconserved Region 339 Promotes Carcinogenesis by Modulating Tumor Suppressor MicroRNAs

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Nov 29

PMID 29180617

Citations 28

Authors

Ivan Vannini

Petra M Wise

Kishore B Challagundla

Meropi Plousiou

Mirco Raffini

Erika Bandini

Francesca Fanini

Giorgia Paliaga

Melissa Crawford

Manuela Ferracin

Cristina Ivan

Linda Fabris

Ramana V Davuluri

Zhiyi Guo

Maria Angelica Cortez

Xinna Zhang

Lu Chen

Shuxing Zhang

Cecilia Fernandez-Cymering

Leng Han

Silvia Carloni

Samanta Salvi

Hui Ling

Mariam Murtadha

Paolo Neviani

Barbara J Gitlitz

Ite A Laird-Offringa

Patrick Nana-Sinkam

Massimo Negrini

Han Liang

Dino Amadori

Amelia Cimmino

George A Calin

Muller Fabbri

Affiliations

Soon will be listed here.

Abstract

The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call "entrapping". Our results support a key role for uc.339 in lung cancer.

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