Abstract
nc886 (= vtRNA2-1 or pre-miR-886) is a recently discovered noncoding RNA that is a cellular PKR (Protein Kinase RNA-activated) ligand and repressor. nc886 has been suggested to be a tumor suppressor, solely based on its expression pattern and genomic locus. In this report, we have provided sufficient evidence that nc886 is a putative tumor suppressor in esophageal squamous cell carcinoma (ESCC). In 84 paired specimens from ESCC patients, nc886 expression is significantly lower in tumors than their normal adjacent tissues. More importantly, decreased expression of nc886 is significantly associated with shorter recurrence-free survival of the patients. Suppression of nc886 is mediated by CpG hypermethylation of its promoter, as evidenced by its significant negative correlation to nc886 expression in ESCC tumors and by induced expression of nc886 upon demethylation of its promoter. Knockdown of nc886 and consequent PKR activation induce FOS and MYC oncogenes as well as some inflammatory genes including oncogenic NF-κB. When ectopically expressed, nc886 inhibits proliferation of ESCC cells, further demonstrating that nc886 could be a tumor suppressor. All these findings implicate nc886 as a novel, putative tumor suppressor that is epigenetically silenced and regulates the expression of oncogenes in ESCC.
Highlights
We have recently identified a 101 nucleotide long non-coding RNA, nc886, that is ubiquitously expressed in normal tissues. nc886 could be a tumor suppressor as suggested by several lines of observations.First, its expression is decreased in cancer cell lines from several tissue origins [1, 2]
As the first step to investigate nc886 in Esophageal cancer (EC), we measured the expression of nc886 in 84 pairs of a tumor tissue and its adjacent normal tissue from esophageal squamous cell carcinoma (ESCC) patients. nc886 expression was significantly suppressed in tumors (Fig 1A-B)
Clinicopathological characteristics of the nc886 high- and lowexpression groups were summarized in Table S1. nc886 expression was decreased in ESCC cell lines (TE1, TE-8, TE-12, and TT) relative to a nonmalignant esophageal cell line Het-1A (Fig 1D)
Summary
Nc886 could be a tumor suppressor as suggested by several lines of observations. Its expression is decreased in cancer cell lines from several tissue origins [1, 2]. RNA ligand and inhibitor of PKR (Protein Kinase RNAactivated), a pleiotropic protein implicated in cellular defense against virus, stress responses, inflammation, and tumorigenesis (reviewed in [7]). Knockdown of nc886 activates PKR and ectopic expression of nc886 represses the interferon response triggered by double-stranded RNA (dsRNA), a canonical PKR activating ligand [1, 2, 8]. Nc886’s function in normal cells is to adjust a cellular level of tolerance to diminutive triggers which should be normally insignificant so that signaling pathways and metabolism are not disturbed. Its molecular roles in tumor development are currently unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
