Exosomal FMR1-AS1 facilitates maintaining cancer stem-like cell dynamic equilibrium via TLR7/NFκB/c-Myc signaling in female esophageal carcinoma

Li, Wei; Zhang, Liyuan; Guo, Binbin; Deng, Jieqiong; Wu, Siqi; Li, Fang; Wang, Yirong; Lü, Jiachun; Zhou, Yifeng

doi:10.1186/s12943-019-0949-7

Cited by 100 publications

(63 citation statements)

References 50 publications

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“…We analyzed the signaling pathway changes and the gene expression changes in each sample. TLR4/NF-κB signaling pathway activation could promote migration and invasiveness of multiple cancers 9,10 . The genes, JUN, involved in the TLR signaling pathway, and ICAM1, involved the NF-κB signaling pathway, were significantly downregulated in GGN-ADC samples.…”

Section: Signaling Pathways Related To Cell Proliferation Were Downrementioning

confidence: 99%

Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules

Yang

Shi

et al. 2020

Cell Discov

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As an early type of lung adenocarcinoma, ground glass nodule (GGN) has been detected increasingly and now accounts for most lung cancer outpatients. GGN has a satisfactory prognosis and its characteristics are quite different from solid adenocarcinoma (SADC). We compared the GGN adenocarcinoma (GGN-ADC) with SADC using the single-cell RNA sequencing (scRNA-seq) to fully understand GGNs. The tumor samples of five patients with lung GGN-ADCs and five with SADCs underwent surgery were digested to a single-cell suspension and analyzed using 10× Genomic scRNA-seq techniques. We obtained 60,459 cells and then classified them as eight cell types, including cancer cells, endothelial cells, fibroblasts, T cells, B cells, Nature killer cells, mast cells, and myeloid cells. We provided a comprehensive description of the cancer cells and stromal cells. We found that the signaling pathways related to cell proliferation were downregulated in GGN-ADC cancer cells, and stromal cells had different effects in GGN-ADC and SADC based on the analyses of scRNA-seq results. In GGN-ADC, the signaling pathways of angiogenesis were downregulated, fibroblasts expressed low levels of some collagens, and immune cells were more activated. Furthermore, we used flow cytometry to isolate the cancer cells and T cells in 12 GGN-ADC samples and in an equal number of SADC samples, including CD4+ T and CD8+ T cells, and validated the expression of key molecules by quantitative real-time polymerase chain reaction analyses. Through comprehensive analyses of cell phenotypes in GGNs, we provide deep insights into lung carcinogenesis that will be beneficial in lung cancer prevention and therapy.

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Section: Signaling Pathways Related To Cell Proliferation Were Downrementioning

confidence: 99%

Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules

Yang

Shi

et al. 2020

Cell Discov

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“…Studies have reported that the long non-coding RNA (lncRNA) RP11 promotes colorectal cancer cells dissemination by ZEB1 overexpression, whereas lncRNA HCCL5 could be activated by ZEB1 to promote hepatocellular carcinoma malignancy. 18,19 Among these, lncRNAs are a class of ncRNAs of more than 200 bp that have been demonstrated to be closely related to cancer progression, including tumorigenesis, 20 stemness, 21 apoptosis, 22 25 It has also been reported that LINC00511 promotes proliferation in pancreatic ductal adenocarcinoma, 26 ovarian cancer 27 and glioma. 16,17 Non-coding RNAs (ncRNAs) are transcribed genes that are not further translated into proteins and include lncRNAs, circular RNAs (circRNAs) and miRNAs, which perform vital roles in human cancers.…”

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confidence: 99%

LINC00511 contributes to glioblastoma tumorigenesis and epithelial‐mesenchymal transition via LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop

Liu

et al. 2019

J Cellular Molecular Medi

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Tumour invasion is closely related to the prognosis and recurrence of glioblastoma multiforme and partially attributes to epithelial‐mesenchymal transition. Long intergenic non‐coding RNA 00511 (LINC00511) plays a pivotal role in tumour; however, the role of LINC00511 in GBM, especially in the epigenetic molecular regulation mechanism of EMT, is still unclear. Here, we found that LINC00511 was up‐regulated in GBM tissues and relatively high LINC00511 expression predicted poorer prognosis. Moreover, ectopic LINC00511 enhanced GBM cells proliferation, EMT, migration and invasion, whereas LINC00511 knockdown had the opposite effects. Mechanistically, we confirmed that ZEB1 acted as a transcription factor for LINC00511 in GBM cells. Subsequently, we found that LINC00511 served as a competing endogenous RNA that sponged miR‐524‐5p to indirectly regulate YB1, whereas, up‐regulated YB1 promoted ZEB1 expression, which inversely facilitated LINC00511 expression. Finally, orthotopic xenograft models were performed to further demonstrate the LINC00511 on GBM tumorigenesis. This study demonstrates that a LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop provides potential therapeutic targets for GBM progression.

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“…Alignments were further analyzed with Cu inks [17] to calculate the abundance (FPKM) of each gene and isoform using the hg19 gene annotations, and with DESeq [18] to identify differentially-expressed splicing factors. To validate the differentially-expressed splicing factors, two microarray datasets, named GSE53624 [18][19] and GSE23400-GPL96 [20][21], were utilized to perform differential expression analysis with the siggenes package in R2.15.3.…”

Section: Methodsmentioning

confidence: 99%

Alterations of RNA Splicing Patterns in Esophagus Squamous Cell Carcinoma

Ding

Cheng

et al. 2020

Preprint

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Abstract Alternative splicing (AS) is an important biological process for regulating the expression of various isoforms from a single gene and thus to promote proteome diversity. In this study, RNA-seq data from 15 pairs of esophageal squamous cell carcinoma (ESCC) tissue samples and two cell lines were analyzed. AS events with significant differences between ESCC and matched normal tissues were re-annotated to find protein coding genes or non-coding RNAs. A total of 45,439 AS events was found. Of these, 6,019 (13.25%) significant differentially AS events were identified. Exon skipping (SE) events occupied the largest proportion of abnormal splicing events. Fifteen differential splicing events with the same trends of ΔΨ values in ESCC tissues and cell lines were found. Four pathways and 20 biological processes related to cell junction and migration were significantly enriched. The upregulated splicing factor SF3B4, which regulates 92 gene splicing events, could be a potential prognostic factor of ESCC. Sashimi plotting was applied to show the differentially-spliced genes, including HNRNPC, VCL, ZNF207, KIAA1217, TPM1 and CALD1. These results suggest that cell junction- and migration-related biological processes and KEGG pathways are affected by the AS abnormalities, and aberrant splicing events can be affected by changed expression of splicing factors. In summary, we identified significant differentially AS events which might be related to the development of ESCC.

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Exosomal FMR1-AS1 facilitates maintaining cancer stem-like cell dynamic equilibrium via TLR7/NFκB/c-Myc signaling in female esophageal carcinoma

Cited by 100 publications

References 50 publications

Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules

Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules

LINC00511 contributes to glioblastoma tumorigenesis and epithelial‐mesenchymal transition via LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop

Alterations of RNA Splicing Patterns in Esophagus Squamous Cell Carcinoma

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