Project description:Background: suitable diagnostic markers for cancers are urgently required in clinical practice. Long noncoding RNAs, which have been reported in many cancer types, are a potential new class of biomarkers for tumor diagnosis. Method: LncRNA gene expression profiles were analyzed in two pairs of human gastric cancer and adjacent non-tumor tissues by microarray analysis. Nine gastric cancer-associated lncRNAs were selected and assessed by quantitative real-time polymerase chain reaction in gastric tissues, and 5 of them were further analyzed in gastric cancer patients’plasma. Results: Five lncRNAs, including AK001058, INHBA-AS1, MIR4435-2HG, UCA1 and CEBPA-AS1 were validated to be increased in gastric cancer tissues. Furthermore, we found that plasma level of these five lncRNAs were significantly higher in gastric cancer patients compared with normal controls. By receiver operating characteristic analysis, we found that the combination of plasma lncRNAs with the area under the curve up to 0.921, including AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, is a better indicator of gastric cancer than their individual levels or other lncRNA combinations. Simultaneously, we found that the expression levels of a series of MIR4435-2HG fragments are different in gastric cancer plasma samples, but most of them higher than that in healthy control plasma samples. Conclusion: Our results demonstrate that certain lncRNAs, such as AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, are enriched in human gastric cancer tissues and significantly elevated in the plasma of patients with gastric cancer. These findings indicate that the combination of these four lncRNAs might be used as diagnostic or prognostic markers for gastric cancer patients.
Project description:ITGB8-AS1 functions as a ceRNA to regulate cell proliferation and tumor growth of colorectal cancer (CRC) via regulating focal adhesion signaling. Targeting ITGB8-AS1 is effective in suppressing CRC cell growth and tumor growth. Elevated plasma levels of ITGB8-AS1 was detected in advanced-stage CRC. Thus, ITGB8-AS1 could serve as a potential therapeutic target and circulating biomarker in CRC.
Project description:Plasma small noncoding RNA levels were measured in breast cancer patients and healthy control women, to determine whether any of these were associated with either patient prognosis, or as diagnostic markers for breast cancer.
Project description:To clarify the function of a long noncoding RNA TM4SF1-AS1 in gastric cancer (GC), we carried out a gene expression microarray analysis using GC cell lines HSC45 transfected with a siRNA targeting TM4SF1-AS1 or a control siRNA. Gene ontology analysis revealed that genes associated with interferon signaling and immune response were significantly enriched among downregulated genes.
Project description:To investigate miRNA expression profiles between gastric cancers plasma and healthy controls plasma,screening the microRNAs that can serve as plasma biomarkers for the early diagnosis of gastric cancer by miRNA array.
Project description:The sensitivity and specificity of traditional non-invasive diagnostic markers for gastric cancer are insufficient. Long-chain noncoding RNAs (lncRNAs) in circulating exosomes are a new class of promising cancer biomarkers. However, the expression profile of long-chain noncoding RNAs (lncRNAs) in exosomes derived from gastric high-grade intraepithelial neoplasia (GHGIN) has not been reported.The aim of this study was to investigate the expression profile of long non-coding RNAs (lncRNAs) in the plasma exosomes of patients with gastric high-grade intraepithelial neoplasia. Peripheral blood samples were collected from five patients with GHGIN and five healthy donors, and the exosomes were isolated. We used high-throughput sequencing to detect differently expressed lncRNAs (DE lncRNAs) in these individuals. Real-time quantitative polymerase chain reaction (RT-qPCR) assay was performed to verify the sequencing results. The potential roles of the DE lncRNAs in GHGIN were speculated by performing Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analysis. We constructed a lncRNAs–miRNA–mRNA network diagram and performed association analyses to explore the underlying molecular mechanisms. A total of 25145 lncRNAs were identified in all samples; 83 lncRNAs that showed significant differential expression were further screened, including 76 up‐regulated and 7 down‐regulated lncRNAs. RT-qPCR further confirmed these results. GO and KEGG analyses predicted that these lncRNAs played important roles in protein and macromolecule glycosylation, regulation of protein ubiquitination, and renin-angiotensin system and MAPK signaling pathways. We further constructed a lncRNA–miRNA–mRNA interaction network. This study may help in discovering new molecular changes, enrich the expression profile of lncRNAs in human GHGIN, and help us better understand the molecular mechanisms of GHGIN and gastric cancer.
Project description:Long noncoding RNAs (lncRNAs) play pivotal roles in tumor development, but little is known about their involvement in the early steps of tumorigenesis. To identify lncRNAs dysregulated in precancerous lesions, we analyzed genome-wide trimethylation of histone H3 lysine 4 (H3K4me3) to screen for transcriptionally active lncRNA genes in the nontumorous gastric mucosa of patients with gastric cancer (GC) and healthy individuals. We found that H3K4me3 at TM4SF1-AS1 is specifically upregulated in GC patients and that expression of TM4SF1-AS1 is prevalently elevated in primary and cultured GC cells. TM4SF1-AS1 contributes to GC cell proliferation in vitro and in vivo, and its oncogenic function is mediated, at least in part, through interaction with Pur-α and YB-1. Chromatin isolation by RNA purification (ChIRP)-mass spectrometry demonstrated that TM4SF1‑AS1 associates with several stress granule (SG)-related proteins, including G3BP2, RACK1 and DDX3. Notably, TM4SF1-AS1 promotes SG formation and inhibits apoptosis in GC cells by sequestering RACK1, an activator of the stress-responsive MAPK pathway, within SGs. TM4SF1‑AS1-induced SG formation and apoptosis inhibition are dependent on Pur-α and YB-1. These findings suggest TM4SF1-AS1 contributes to tumorigenesis by enhancing SG-mediated stress adaptation.
Project description:This is a comparative study. This study is to compare the diagnostic sensitivity between circulating tumor DNA methylation and carcinoembryonic antigen in detecting colorectal cancer. There are two steps in this study. Firstly, the diagnostic model is established based on tumor-specific plasma circulating tumor DNA methylation markers. Secondly, the sensitivity, specificity and accuracy of plasma circulating tumor DNA methylation are compared with that of carcinoembryonic antigen in detecting colorectal cancer.
Project description:Characterisation IER3-AS1 interacting proteins using chromatin oligo-affinity precipitation (ChOP) followed by mass spectrometry. The HeLa cell lysates was incubated with biotinylated antisense oligonucleotides (ASO), targeting an experimental target antisense long noncoding RNA IER3-AS1 or a control RNA LacZ. LacZ and IER3-AS1 interacting proteomes were pulldown using Streptavidin beads. The eluted protein samples from both LacZ control ASOs and IER3-AS1 ASOs subjected to mass-spectrometry analyses to identify IER3-AS1 interacting proteins.
Project description:Circular RNAs, a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC. We found that CircGSK3beta exerts critical roles in promoting ESCC metastasis and may serve as an exploitable therapeutic target for patients with ESCC. The plasma level of circGSK3beta have promising potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.