The long non-coding RNA LINC01606 contributes to the metastasis and invasion of human gastric cancer and is associated with Wnt/β-catenin signaling

Luo, Yang; Tan, Wanlong; Jia, Weikun; Liu, Zilin; Ye, Pengcheng; Fu, Zhiming; Lu, Fei; Xiang, Wanping; Tang, Lixia; Lin, Yu; Huang, Qingmei; Xiao, Jiangwei

doi:10.1016/j.biocel.2018.08.012

Cited by 30 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, the infertility associated CpG module is hypermethylated on chromosome 8 locus in sperm from infertile men, and is located nearby the upstream of LINC01606, a testis-selective long-noncoding RNA gene. LINC01606 has been shown to be elevated aberrantly and correlated with metastasis and invasion of gastric cancer, and its expression level is associated with Wnt/β-catenin signaling pathway activation through the regulation of miR-423-5P [ 45 ]. There is no evidence yet that LINC01606 plays a role in spermatogenesis or male fertility, but whether the hypermethylated CpG module is correlated to this long non-coding RNA gene in infertile men, and which miRNA species are subsequently regulated by LINC01606 in human sperm is worth considering for further study.…”

Section: Discussionmentioning

confidence: 99%

High-resolution analyses of human sperm dynamic methylome reveal thousands of novel age-related epigenetic alterations

et al. 2020

View full text Add to dashboard Cite

Background Children of aged fathers are at a higher risk of developing mental disorders. Alterations in sperm DNA methylation have been implicated as a potential cause. However, age-dependent modifications of the germ cells’ epigenome remain poorly understood. Our objective was to assess the DNA methylation profile of human spermatozoa during aging. Results We used a high throughput, customized methylC-capture sequencing (MCC-seq) approach to characterize the dynamic DNA methylation in spermatozoa from 94 fertile and infertile men, who were categorized as young, 48 men between 18–38 years or old 46 men between 46–71 years. We identified more than 150,000 age-related CpG sites that are significantly differentially methylated among 2.65 million CpG sites covered. We conducted machine learning using our dataset to predict the methylation age of subjects; the age prediction accuracy based on our assay provided a more accurate prediction than that using the 450 K chip approach. In addition, we found that there are more hypermethylated (62%) than hypomethylated (38%) CpG sites in sperm of aged men, corresponding to 798 of total differential methylated regions (DMRs), of which 483 are hypermethylated regions (HyperDMR), and 315 hypomethylated regions (HypoDMR). Moreover, the distribution of age-related hyper- and hypomethylated CpGs in sperm is not random; the CpG sites that were hypermethylated with advanced age were frequently located in the distal region to genes, whereas hypomethylated sites were near to gene transcription start sites (TSS). We identified a high density of age-associated CpG changes in chromosomes 4 and 16, particularly HyperDMRs with localized clusters, the chr4 DMR cluster overlaps PGC1α locus, a protein involved in metabolic aging and the chr16 DMR cluster overlaps RBFOX1 locus, a gene implicated in neurodevelopmental disease. Gene ontology analysis revealed that the most affected genes by age were associated with development, neuron projection, differentiation and recognition, and behaviour, suggesting a potential link to the higher risk of neurodevelopmental disorders in children of aged fathers. Conclusion We identified thousands of age-related and sperm-specific epigenetic alterations. These findings provide novel insight in understanding human sperm DNA methylation dynamics during paternal aging, and the subsequently affected genes potentially related to diseases in offspring.

show abstract

Section: Discussionmentioning

confidence: 99%

High-resolution analyses of human sperm dynamic methylome reveal thousands of novel age-related epigenetic alterations

et al. 2020

View full text Add to dashboard Cite

show abstract

“…LncRNA HOTAIR is negatively correlated with miR-34a level; that is, overexpression of HOTAIR decreases the miR-34a level and leads to the activation of the WNT/β-catenin pathway; this phenomenon coincides with increased cellular proliferation77. Similarly, lncRNA FEZF1-AS1 and lncRNA LINC01606, whose expression levels are upregulated in GC cells, activate Wnt/β-catenin signaling to promote tumor cell migration and invasion78, 79. LncRNA LINC01133 and ENST00000434223 are downregulated in GC tissues and cell lines, and its low expression is positively correlated with EMT and metastasis by inactivating the Wnt/β-catenin pathway80, 81.…”

Section: Wnt Pathway-related Lncrnas and Gcmentioning

confidence: 99%

The roles of Wnt/β-catenin signaling pathway related lncRNAs in cancer

Hu¹,

Hou²,

Li³

et al. 2018

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs), with length of more than 200 nucleotides, are not translated into proteins but involved in multiple diverse diseases, especially tumorigenesis. The dysregulation of lncRNAs greatly contributes to the progression of various tumors through specific signaling pathways, including Wnt/β-catenin signaling pathway, which is associated with malignant features of tumors. The interactions between lncRNAs, which have specific expression characteristics in diverse cancer tissues, and Wnt/β-catenin signaling pathway, exhibit potential as novel biomarkers and therapeutic targets. In this review, we aim to present research findings on the roles of Wnt pathway-related lncRNAs and their effects on Wnt/β-catenin signaling to regulate tumorigenesis in different cancer types. Results may be used as basis to develop or improve strategies for treatment of different carcinomas.

show abstract

“…An increasing number of recent studies have revealed that lncRNAs participate in the progression of GC by regulating metastasis and angiogenesis 11 . The ncRNAs Z38 12 , LINC01606 13 , and SNHG16 regulate cell metastasis in GC. LINC01410 14 , PVT1 15 , and MALAT1 16 contribute to the regulation of vasculogenic mimicry and angiogenesis, which can in turn aggravate GC progression.…”

Section: Introductionmentioning

confidence: 99%

LncRNA AC093818.1 accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression

Long

et al. 2020

Cell Death Dis

View full text Add to dashboard Cite

Gastric cancer (GC) is a highly prevalent type of metastatic tumor. The mechanisms underlying GC metastasis are poorly understood. Some long noncoding RNAs (lncRNAs) reportedly play key roles in regulating metastasis of GC. However, the biological roles of five natural antisense lncRNAs (AC093818.1, CTD-2541M15.1, BC047644, RP11-597M12.1, and RP11-40A13.1) in GC metastasis remain unclear. In this study, the expression of these lncRNAs was measured by quantitative reverse transcription-polymerase chain reaction. Migration and invasion were evaluated by wound-healing and the Transwell assay, respectively. Stable cells were injected into the tail veins of nude mice. Sections of collected lung and liver tissues were stained using hematoxylin and eosin. Protein expression was analyzed by western blot. RNA immunoprecipitation (RIP) assay was used to verify whether the STAT3 and SP1 transcription factors bound to AC093818.1 in GC cells. Expression levels of the five lncRNAs, especially AC093818.1, were significantly upregulated in metastatic GC tissues relative to those in nonmetastatic GC tissues. AC093818.1 expression was correlated with invasion, lymphatic metastasis, distal metastasis, and tumor-node-metastasis stage. AC093818.1 expression was highly sensitive and specific in the diagnosis of metastatic or nonmetastatic GC. AC093818.1 overexpression promoted GC migration and invasion in vitro and in vivo. AC093818.1 overexpression increased PDK1, p-AKT1, and p-mTOR expression levels. AC093818.1 silencing decreased these expressions. AC093818.1 bound to transcription factors STAT3 and SP1, and SP1 or STAT3 silencing could alleviated the effect of AC093818.1 overexpression. The data demonstrate that lncRNA AC093818.1 accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression. LncRNA AC093818.1 may be a potential therapeutic target for metastatic GC.

show abstract

The long non-coding RNA LINC01606 contributes to the metastasis and invasion of human gastric cancer and is associated with Wnt/β-catenin signaling

Cited by 30 publications

References 34 publications

High-resolution analyses of human sperm dynamic methylome reveal thousands of novel age-related epigenetic alterations

High-resolution analyses of human sperm dynamic methylome reveal thousands of novel age-related epigenetic alterations

The roles of Wnt/β-catenin signaling pathway related lncRNAs in cancer

LncRNA AC093818.1 accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression

Contact Info

Product

Resources

About