Abnormal expression of FOSB correlates with tumor progression and poor survival in patients with gastric cancer

Tang, Chong; Jiang, Yasu; Shao, Weiwei; Shi, Wen; Gao, Xuesong; Qin, Weiyan; Jiang, Tian; Wang, Feiran; Feng, Shichun

doi:10.3892/ijo.2016.3661

Cited by 24 publications

(22 citation statements)

References 22 publications

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“…As previously demonstrated, some of the fifteen genes serve crucial roles in GC [ 45 – 47 ]. For example, Tang et al have demonstrated that FOSB was significantly decreased in GC tissues, consistent with the results of this study, and moreover, downregulated expression of FOSB was correlated with poor prognosis for GC patients [ 46 ].…”

Section: Discussionsupporting

confidence: 90%

Identification of circRNA–miRNA–mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer

et al. 2021

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Background Circular RNAs (circRNAs) are a new class of noncoding RNAs that have gained increased attention in human tumor research. However, the identification and function of circRNAs are largely unknown in the context of gastric cancer (GC). This study aims to identify novel circRNAs and determine their action networks in GC. Methods A comprehensive strategy of data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology were conducted to discover novel circRNAs and to explore their potential mechanisms in GC. Promising therapeutic drugs for GC were determined by connectivity map (CMap) analysis. Results Six overlapped differentially expressed circRNAs (DECs) were screened from selected microarray and RNA-Seq datasets of GC, and the six DECs were then validated by sanger sequencing and RNase R treatment. Subsequent RT-qPCR analysis of GC samples confirmed decreased expressions of the six DECs (hsa_circ_0000390, hsa_circ_0000615, hsa_circ_0001438, hsa_circ_0002190, hsa_circ_0002449 and hsa_circ_0003120), all of which accumulated preferentially in the cytoplasm. MiRNA binding sites and AGO2 occupation of the six circRNAs were predicted using online databases, and circRNA–miRNA interactions including the six circRNAs and 33 miRNAs were determined. Then, 5320 target genes of the above 33 miRNAs and 1492 differently expressed genes (DEGs) from The Cancer Genome Atlas (TCGA) database were identified. After intersecting the miRNA target genes and the 889 downregulated DEGs, 320 overlapped target genes were acquired. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these target genes were related to two critical tumor-associated signaling pathways. A protein–protein interaction network with the 320 target genes was constructed using STRING, and fifteen hubgenes (ATF3, BTG2, DUSP1, EGR1, FGF2, FOSB, GNAO1, GNAI1, GNAZ, GNG7, ITPR1, ITPKB, JUND, NR4A3, PRKCB) in the network were identified. Finally, bioactive chemicals (including vorinostat, trichostatin A and astemizole) based on the fifteen hubgenes were identifed as therapeutic agents for GC through the CMap analysis. Conclusions This study provides a novel insight for further exploration of the pathogenesis and therapy of GC from the circRNA-miRNA-mRNA network perspective.

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Section: Discussionsupporting

confidence: 90%

Identification of circRNA–miRNA–mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer

et al. 2021

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“…TNFa gene expression was down-regulated by the knockdown of AC009283.1 and TNFa up-regulation has also been shown to increase cellular proliferation 39 . The oncogene FOSB was up-regulated after AC009283.1 knockdown, and FOSB has been associated with suppressed cell proliferation in gastric cancer cell lines 40 . In vitro assays (automated cell counting, proliferation index and cycle cell assay by flow cytometry) confirmed that knockdown of AC009283.1 reduced proliferation and decreased S phase in SKBR3 cells, potentially through the modulation of NOCTH3 , TNFa and FOSB genes.…”

Section: Discussionmentioning

confidence: 93%

A lncRNA landscape in breast cancer reveals a potential role for AC009283.1 in proliferation and apoptosis in HER2-enriched subtype

Cedro‐Tanda

Ríos-Romero

Romero-Córdoba

et al. 2020

Sci Rep

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Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized heterogeneous pathology, classified into four molecular subtypes: Luminal A, Luminal B, HER2enriched and Basal-like, each one with different biological and clinical characteristics. Long noncoding RNAs (lncRNAs) represent 33% of the human transcriptome and play critical roles in breast carcinogenesis, but most of their functions are still unknown. Therefore, cancer research could benefit from continued exploration into the biology of lncRNAs in this neoplasm. We characterized lncRNA expression portraits in 74 breast tumors belonging to the four molecular subtypes using transcriptome microarrays. To infer the biological role of the deregulated lncRNAs in the molecular subtypes, we performed co-expression analysis of lncRNA-mRNA and gene ontology analysis. We identified 307 deregulated lncRNAs in tumor compared to normal tissue and 354 deregulated lncRNAs among the different molecular subtypes. Through co-expression analysis between lncRNAs and proteincoding genes, along with gene enrichment analysis, we inferred the potential function of the most deregulated lncRNAs in each molecular subtype, and independently validated our results taking advantage of TCGA data. Overexpression of the AC009283.1 was observed in the HER2-enriched subtype and it is localized in an amplification zone at chromosome 17q12, suggesting it to be a potential tumorigenic lncRNA. The functional role of lncRNA AC009283.1 was examined through loss of function assays in vitro and determining its impact on global gene expression. These studies revealed that AC009283.1 regulates genes involved in proliferation, cell cycle and apoptosis in a HER2 cellular model. We further confirmed these findings through ssGSEA and CEMITool analysis in an independent HER2-amplified breast cancer cohort. Our findings suggest a wide range of biological functions for lncRNAs in each breast cancer molecular subtype and provide a basis for their biological and functional study, as was conducted for AC009283.1, showing it to be a potential regulator of proliferation and apoptosis in the HER2-enriched subtype.

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“…Between the most differentially expressed and upregulated genes under hypoxia and glucose deprivation are KRT17, GADD34/PPP1R15A, ETS1, DDIT4/REDD1, HK2, PFKFB3, DDIT3, SLC2A3, TAGLN, SLC22A15, SH3D21, DEPP1, RORA, ANGPTL4, ELOVL6 , FOSB , LMNB1 , and EGR1 . Together, these constitute a panel of biotic stress activated genes driving systemic changes at the transcriptomic level towards more undifferentiated ( KRT17 , FOSB ) 30,31 , poorly proliferative ( LMNB1 ) 32,33 , and less prone to programmed cell death and anoikis ( GADD34/PPP1R15A , DDIT4/REDD1 , PFKFB3 , ANGPTL4 ) phenotypes 34–37 . Moreover, the negative regulation of suppressor factors ( EGR1) 38 , allied to the promotion of immunosuppressor or tolerogenic ( GADD34/PPP1R15A, DDIT3) programs 39–43 leads to enhanced invasive/migratory ( ETS1 , DDIT4/REDD1 , TAGLN ) capacities 44–46 , as previously demonstrated.…”

Section: Resultsmentioning

confidence: 99%

Metabolomics, Transcriptomics and Functional Glycomics Reveals Bladder Cancer Cells Plasticity and Enhanced Aggressiveness Facing Hypoxia and Glucose Deprivation

Peixoto

Freitas

Ferreira

et al. 2021

Preprint

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Bladder cancer constitutes one of the deadliest genitourinary diseases, especially when diagnosed at late stages. These tumours harbour microenvironmental niches characterized by low levels of oxygen (hypoxia) and limited glucose supply due to poor vascularization. However, the synergic contribution of these features to disease development is poorly understood. Here, we demonstrated that cells with distinct histopathological and molecular backgrounds responded similarly to such stimuli. Cancer cells arrested proliferation, significantly increased invasive capacity in vitro and enhanced tolerance to cisplatin-based chemotherapy. Reoxygenation and access to glucose restored basal proliferation and invasion levels without triggering stress-induced apoptosis, denoting significant cellular plasticity in adapting to microenvironmental cues. Whole transcriptomics showed major molecular reprogramming, supporting main functional alterations. Metabolomics evidenced fatty acids β-oxidation as main bioenergetic pathway rather than anaerobic glycolysis generally adopted by hypoxic cells. Joint pathway analysis also suggested relevant alterations in mucin-type O-glycan biosynthesis. Glycomics confirmed a major antagonization of O-glycosylation pathways, leading to simple cell glycophenotypes characterized by the accumulation of immature short-chain O-glycans such as Tn and STn antigens at the cell surface. Glycoengineered models reflecting simple cell glycophenotypes were developed and functional studies in vitro and in vivo showed that Tn and STn overexpression decreased proliferation and promoted chemoresistance, reinforcing their close link with tumour aggressiveness. Collectively, we have demonstrated that hypoxia and glucose deprivation trigger more aggressive cell behaviours, in what appears to be an escape mechanism from microenvironmental stress. We propose that, altered glycosylation may be used to target these subpopulations, paving the way for precision oncology.

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Abnormal expression of FOSB correlates with tumor progression and poor survival in patients with gastric cancer

Cited by 24 publications

References 22 publications

Identification of circRNA–miRNA–mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer

Identification of circRNA–miRNA–mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer

A lncRNA landscape in breast cancer reveals a potential role for AC009283.1 in proliferation and apoptosis in HER2-enriched subtype

Metabolomics, Transcriptomics and Functional Glycomics Reveals Bladder Cancer Cells Plasticity and Enhanced Aggressiveness Facing Hypoxia and Glucose Deprivation

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