Role of DiGeorge syndrome critical region gene 9, a long noncoding RNA, in gastric cancer

Emerging evidence have indicated that dysregulated long noncoding ribonucleic acids act as a novel diagnostic and therapeutic target in the progression of ovarian cancer. Long noncoding RNA DiGeorge syndrome critical region gene 5 has been reported to participate in some types of human cancer progresses, but its clinical roles in ovarian cancer had been rarely reported. This study aimed to explore the expression, clinicopathological features, diagnostic, and prognostic values of DiGeorge syndrome critical region gene 5 in ovarian cancer. The total levels of DiGeorge syndrome critical region gene 5 transcript variant 1 (NR_002733.2) and 2 (NR_045121.1) in patients with ovarian cancer were determined by quantitative reverse transcription polymerase chain reaction. The correlation of DiGeorge syndrome critical region gene 5 expression with clinicopathological factors was statistically analyzed by χ2 test. Overall survival analysis was carried out with the Kaplan–Meier curves with the log-rank test. Univariate and multivariate Cox regression analyses were performed to identify the prognostic significance of DiGeorge syndrome critical region gene 5 expression. Receiver operating characteristic curves were constructed to estimate the diagnostic and prognostic usefulness of DiGeorge syndrome critical region gene 5 in ovarian cancer. Results showed that relative DiGeorge syndrome critical region gene 5 expression was reduced by 36.81% and 65.79% in ovarian cancer tissues of patients and Gene Expression Omnibus DataSets (GSE119056) in contrast to normal tissues, respectively. Patients with lymph node metastasis and distant metastasis exhibited lower levels of DiGeorge syndrome critical region gene 5 in contrast to those patients with non-lymph node metastasis and non-distant metastasis, respectively. Low expression of DiGeorge syndrome critical region gene 5 was significantly associated with large tumor size, more lymph node metastasis, present distant metastasis, advanced clinical stage, and short overall survival in patients with ovarian cancer. Low expression of DiGeorge syndrome critical region gene 5 was an independent unfavorable prognostic factor for overall survival in patients with ovarian cancer. Receiver operating characteristics curves for prognosis yielded significant area under curves for lymph node metastasis, clinical stage, and overall survival. In conclusion, our study demonstrated that downregulated DiGeorge syndrome critical region gene 5 may be a new promising biomarker for predicting clinical progression and prognosis in patients with ovarian cancer.

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Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00873-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yan Zhang ◽

Lin Chen ◽

Xuanting Ye ◽

Zhixiong Wu ◽

Zeyu Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Parameter Analysis ◽

Cell Proliferation And Migration ◽

Potential Biomarker ◽

And Migration ◽

Proliferation And Migration

Abstract Background Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC. Results The prepared CD63 immunomagnetic beads (CD63-IMB) had the characteristics of good dispersity and high magnetic response. The isolated exosomes were presented with elliptical membranous particles under a transmission electron microscope (TEM), with the particle size of 89.78 ± 4.8 nm. Western blot (WB) results showed that the exosomes were rich in CD9 and CD81. The Dil-labeled exosomes were distributed around cytoplasm and nucleus of cells by imaging flow cytometry (IFC) analysis. The results of quantitative real-time PCR (qRT-PCR) revealed that the FRLnc1 expressions were up-regulated in GC cells, tumor tissues, and serum of GC patients. An obviously up-regulated FRLnc1 expression was found in serum exosomes of GC patients. Up-regulation of FRLnc1 expression was closely correlated to lymph node metastasis (LNM) and TNM stage with the combination of relevant clinicopathological parameter analysis. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell proliferation and migration in HGC-27 cells, whereas FRLnc1 overexpression promoted cell proliferation and migration in MKN45 cells. After exosome treatment, the FRLnc1 expression was significantly increased in MKN45 cells, and the MKN45 cells showed increased ability of proliferation and migration. Conclusion GC cells-derived exosomes played roles in promoting the growth and metastasis of GC by transporting FRLnc1, suggesting that FRLnc1 in the exosomes may be a potential biomarker for the diagnosis and treatment of GC. The delivery of FRLnc1 by the exosomes may provide a new way for the treatment of GC. Trial registration 2020-KYSB-094. Registered 23 March 2020—Retrospectively registered Graphic abstract

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Long noncoding RNA CCAT1 rs67085638 SNP contribution to the progression of gastric cancer in a Polish population

Scientific Reports ◽

10.1038/s41598-021-94576-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tomasz Olesiński ◽

Anna Lutkowska ◽

Adam Balcerek ◽

Anna Sowińska ◽

P Piotrowski ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Insertion Site ◽

Leukaemia Virus ◽

Node Metastasis ◽

Melting Analysis

AbstractThe role of the long noncoding RNA CCAT1 NC_000008.10:g.128220661C > T (rs67085638) in the development of colon cancer has been reported. Therefore, we assessed the prevalence of rs67085638 in patients with gastric cancer (GC). We also evaluated the effect of rs67085638 on B-cell-specific Moloney leukaemia virus insertion site 1 (BMI1) transcripts in primary GC and counterpart histopathologically confirmed disease-free margin tissue. Using high-resolution melting analysis, we evaluated rs67085638 frequency in patients with the GC genotype (n = 214) and controls (n = 502) in a Polish Caucasian population. qRT-PCR was used to determine BMI1 transcripts. We observed the trend of rs67085638 association in all patients with GC (ptrend = 0.028), a strong risk of the GC genotype in male (ptrend = 0.035) but not female (ptrend = 0.747) patients, and the association with non-cardia GC (ptrend = 0.041), tumour stages T3 (ptrend = 0.014) and T4 (ptrend = 0.032), differentiation grading G3 (ptrend = 0.009), lymph node metastasis stage N3 (ptrend = 0.0005) and metastasis stage M0 (ptrend = 0.027). We found that significantly increased BMI1 transcripts were associated with the primary GC genotype classified as grade G3 (p = 0.011) and as lymph node metastasis N3 (p = 0.010) and counterpart marginal tissues (p = 0.026, p = 0.040, respectively) from carriers of the T/T versus C/C genotypes. rs67085638 may contribute to increased BMI1 transcripts and the progression and rapid growth of GC.

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MALAT1 Induces Fibroblast Activation to Promote Cancer Progression via Blunting Autophagic Flux and Instigating IL-6 Secretion in Gastric Cancer Cells

10.21203/rs.3.rs-88665/v1 ◽

2020 ◽

Author(s):

Zhen-qiang Wang ◽

Xin-jing Wang ◽

Tian-qi Zhang ◽

Li-ping Su ◽

Bingya Liu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Rna Binding ◽

Autophagic Flux ◽

Gastric Cancer Cells ◽

Intercellular Interaction ◽

Autophagy Inhibition

Abstract BackgroundAutophagy defection contributes to inflammation dysregulation, which plays an important role in gastric cancer (GC) progression. Various studies have demonstrated that long noncoding RNA could function as novel regulators of autophagy. However, the epigenetic regulatory mechanisms by which blockage of autophagy caused by long noncoding RNAs develops cancer progression remain unclear. This study aimed to investigate the role of the long noncoding RNA MALAT1 in the autophagy related inflammation dysregulation of GC progression and elucidate the underlying molecular mechanisms.MethodsThe effect of MALAT1 on autophagy in GC cells was analysed by immunoblotting, immunofluorescence and transmission electron microscopy. The role of MALAT1 in regulating inflammation dysregulation was evaluated by ELISA, qPCR and immunoblotting. Bioinformatic prediction, RNA immunoprecipitation-qRCP and immunofluorescence were performed to identify the competitive binding relationship among MALAT1, ELAVL1 and PTEN 3'-UTRs.The chromatin immunoprecipitation assay was performed to examine STAT3 interaction in the MALAT1 promoter region. Immunoblotting was performed to identify the PTEN/AKT/mTOR and SQSTM1/NF-kb mediated pathways altered by MALAT1. The influence of MALAT1 on fibroblasts activation were determined both in in vitro and in vivo.ResultsWe found that the long noncoding RNA MALAT1 could promote interleukin-6 (IL-6) secretion in GC cells by blocking autophagic flux. Moreover, IL-6 induced by MALAT1 could activate normal to cancer-associated fibroblast conversion. The interaction between GC cells and cancer-associated fibroblasts in the tumour microenvironment could facilitate cancer progression. Mechanistically, MALAT1 overexpression destabilized the PTEN mRNA in GC cells by competitively interacting with the RNA-binding protein ELAVL1 to activate the AKT/mTOR pathway for impairing autophagic flux. As the consequence of autophagy inhibition, SQSTM1 accumulation promotes NF-κB translocation to elevate IL-6 expression. Furthermore, STAT3 induced by IL-6 is responsible for upregulation of MALAT1 in GC.ConclusionsOverall, these results demonstrated that intercellular interaction between GC cells and fibroblasts was mediated by autophagy inhibition caused by increased MALAT1 that promote GC progression, providing novel prevention and therapeutic strategies for GC.

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Faculty Opinions recommendation of SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725372335.793505148 ◽

2015 ◽

Author(s):

Luc DesGroseillers

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Mrna Stability ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Proliferation And Apoptosis

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LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM

Molecular Cancer ◽

10.1186/s12943-020-01299-y ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Feifei Zhang ◽

Hui Wang ◽

Jiang Yu ◽

Xueqing Yao ◽

Shibin Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Alternative Splicing ◽

Noncoding Rna ◽

De Novo ◽

Acquired Resistance ◽

Genetic Alterations ◽

Clinical Samples ◽

Autophagy Flux ◽

Resistance To Chemotherapy

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.

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LncRNA DiGeorge syndrome critical region gene 5: A crucial regulator in malignant tumors

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111889 ◽

2021 ◽

Vol 141 ◽

pp. 111889

Author(s):

Haoming Xia ◽

Ziyue Huang ◽

Shuqiang Liu ◽

Xudong Zhao ◽

Risheng He ◽

...

Keyword(s):

Critical Region ◽

Digeorge Syndrome ◽

Malignant Tumors ◽

Region Gene

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Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02149-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zimo Zhou ◽

Mohammad Showkat Hossain ◽

Da Liu

Keyword(s):

Bone Regeneration ◽

Osteogenic Differentiation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Osteoblast Differentiation ◽

Osteoclast Differentiation ◽

Complex Processes ◽

Osteogenic Induction ◽

Novel Target

AbstractOsteogenic differentiation and bone regeneration are complex processes involving multiple genes and multiple steps. In this review, we summarize the effects of the long noncoding RNA (lncRNA) H19 on osteogenic differentiation.Osteogenic differentiation includes matrix secretion and calcium mineralization as hallmarks of osteoblast differentiation and the absorption of calcium and phosphorus as hallmarks of osteoclast differentiation. Mesenchymal stem cells (MSCs) form osteoprogenitor cells, pre-osteoblasts, mature osteoblasts, and osteocytes through induction and differentiation. lncRNAs regulate the expression of coding genes and play essential roles in osteogenic differentiation and bone regeneration. The lncRNA H19 is known to have vital roles in osteogenic induction.This review highlights the role of H19 as a novel target for osteogenic differentiation and the promotion of bone regeneration.

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