Open AccessOverexpression of ultraconserved region 83- induces lung cancer tumorigenesis
Author(s) -
Ivan Vannini,
Manuela Ferracin,
Francesco Fabbri,
Muller Fabbri
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0261464
Subject(s) - carcinogenesis , biology , cancer research , downregulation and upregulation , long non coding rna , lung cancer , gene , cell growth , microarray analysis techniques , rna , gene expression , genetics , medicine , pathology
The expression of non–coding RNAs (ncRNAs) is dysregulated in human cancers. The transcribed ultraconserved regions (T-UCRs) express long ncRNAs involved in human carcinogenesis. T-UCRs are non-coding genomic sequence that are 100% conserved across humans, rats and mice. Conservation of genomic sequences across species intrinsically implies an essential functional role and so we considered the expression of T-UCRs in lung cancer. Using a custom microarray we analyzed the global expression of T-UCRs. Among these T-UCRs, the greatest variation was observed for antisense ultraconserved element 83 ( uc . 83- ), which was upregulated in human lung cancer tissues compared with adjacent non cancerous tissues. Even though uc . 83- is located within the long intergenic non-protein coding RNA 1876 ( LINC01876 ) gene, we found that the transcribed uc . 83- is expressed independently of LINC01876 and was cloned as a 1143-bp RNA gene. In this study, functional analysis confirmed important effects of uc . 83- on genes involved in cell growth of human cells. siRNA against uc . 83- decreased the growth of lung cancer cells while the upregulation through a vector overexpressing the uc . 83- RNA increased cell proliferation. We also show the oncogenic function of uc . 83- is mediated by the phosphorylation of AKT and ERK 1/2, two important biomarkers of lung cancer cell proliferation. Based on our findings, inhibition against uc . 83- could be a future therapeutic treatment for NSCLC to achieve simultaneous blockade of pathways involved in lung carcinogenesis.