Methylation-mediated downregulation of long noncoding RNA LOC100130476 in gastric cardia adenocarcinoma

Abstract

Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play important roles in several biological processes and dysregulated lncRNAs are involved in different kinds of cancer and are associated with carcinogenesis, metastasis, and prognosis of cancer. The role of a new lncRNA LOC100130476 in gastric cardia adenocarcinoma (GCA) has remained unknown. The present study investigated the role and methylation status of LOC100130476 in the pathogenesis of GCA, and further evaluated the potential prognostic role of LOC100130476 in GCA. Significant downregulation of LOC100130476 was detected in SGC-7901 and BGC-823 cell lines and primary GCA tissues. Methylation frequency of LOC100130476 was gradually increased from exon 1 to exon 2 both in tumor tissues and corresponding normal tissues; however, methylation status of region 1 closing to the transcription start site was more tumor-specific among the three regions examined. The findings of the association between LOC100130476 expression, methylation and TNM stage, pathological differentiation, and GCA patients' survival further identified the role of LOC100130476 as a tumor suppressor gene. Furthermore, the hypermethylation of LOC100130476 was also detected in peripheral white blood cells of GCA cases. Thus, LOC100130476 may be act as a tumor suppressor gene in GCA carcinogenesis and aberrant methylation at the CpG sites near the transcription start site within exon 1 may be critical for gene silencing. In addition, aberrant methylation of LOC100130476 in peripheral white blood cells and GCA tissues may be used as a potential valuable biomarker in GCA diagnosis and prognosis.

WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

“…Moreover, at the promoter of WAKMAR2, we used PROMO software, version 3.0.2, to identify several putative binding sites of transcription factors known to interact with Smad complexes, for example, AP1, HNF-1B, HOXD9, and HOXD10, as well as nuclear receptors like the glucocorticoid receptors a and b, supporting our findings of TGF-beinduced WAKMAR2 expression (Farré et al, 2003;Messeguer et al, 2002). Of note, WAKMAR2 was recently reported to be downregulated in esophageal squamous cell carcinoma and gastric cardia adenocarcinoma due to aberrant hypermethylation of CpG islands (Guo et al, 2016a(Guo et al, , 2016b. We noticed that the potential binding sites of Smad3 and several aforementioned transcription factors, for example, AP-1, glucocorticoid receptor a/b, HOXD9, and HOXD10, co-localized with CpG islands at the WAKMAR2 = (d) Luciferase activity was measured in keratinocytes transfected with NF-kB reporter and Ctr or GapmeR1 for 24 hours and treated with TNF-a for 1 or 3 hours (n ¼ 4).…”

A long noncoding RNA, lincRNA‐Tnfaip3, acts as a coregulator of NF‐κB to modulate inflammatory gene transcription in mouse macrophages

“…Another lincRNA induced in mouse macrophages after LPS stimulation is located at mouse chromosome 10 proximal to the tumor necrosis factor a-induced protein 3 (Tnfaip3) gene (27). An ortholog transcript in human is LOC100130476, located on 6q23.3 (GRCh38/hg38, from chr6:137823670 to 137868233, NR_049793.1) (28,29). The potential function of this lincRNA in regulation of inflammatory responses in macrophages is unclear.…”

Serum lincRNA‐p21 as a potential biomarker of liver fibrosis in chronic hepatitis B patients

“…By contrast, lincRNA‐p21 was significantly reduced in a time‐dependent manner (Figure C). Increasing evidence shows that aberrant methylation may be responsible for lncRNAs down‐regulation in various human diseases . Using bioinformatic analysis, there was a CpG island in the promoter of lincRNA‐p21 (Figure D).…”