p53R2 overexpression in cervical cancer promotes AKT signaling and EMT, and is correlated with tumor progression, metastasis and poor prognosis

Jiang, Chao; Xu, Rui; Li, Xiao Xing; Wang, Yan Yan; Liang, Wen Qian; Zeng, Ju Deng; Zhang, Shan Shan; Xu, Xiao; Yang, Yang; Zhang, Mei Yin; Wang, Huiyun; Zheng, Xiaohui

doi:10.1080/15384101.2017.1320629

Cited by 18 publications

(14 citation statements)

References 45 publications

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“…[19][20][21] Moreover, it has been confirmed that activated PI3K/AKT is correlated with the progression and metastasis of cervical cancer cells. [22] In this study, knockdown of USP18 deeply suppressed the phosphorylation of AKT in cervical cancer cells. The PI3K/AKT inhibitor LY294002 deeply suppressed the function of oeUSP18 in cervical cancer cells.…”

Section: Discussionmentioning

confidence: 61%

USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway

Diao

Guo

Zhu

et al. 2020

Preprint

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Background: The deubiquitinating (DUB) enzyme ubiquitin-specific protease 18 (USP18), also known as UBP43, is an ubiquitin-specific protease and has been linked to several human malignancies. However, the underlying function of USP18 remains unclear in human cervical cancer. In the current research, we aimed to analyze the role of USP18 and its signaling pathway in cervical cancer. Methods: Quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to analyze USP18 levels in cervical cancer and adjacent-matched tissues. Moreover, RNA interference (RNAi) and lentiviral-mediated vector were performed to silence and overexpression of USP18 in cervical cancer cells. Further, Cell Counting Kit-8 (CCK-8) assay and Annexin V/PI staining were used to assess its biological function in cell proliferation and apoptosis respectively. Results: Present findings demonstrated that USP18 was overexpressed in cervical cancer specimens and cell lines. Silencing of USP18 in cervical cancer cell lines, SiHa and Caski, inhibited cell proliferation, while induced apoptosis and promoted the expression of cleaved caspase-3. On the contrary, USP18 overexpression showed reversed effects in Hela cells. Gene Set Enrichment Analysis suggested that USP18 was enriched in PI3K/AKT signaling pathway in cervical cancer. Hence, the PI3K/AKT inhibitor LY294002 was used to determine the relationship between USP18 and AKT in cervical cancer cells. Importantly, the PI3K/AKT inhibitor LY294002 deeply abolished the effects of USP18 overexpression in cervical cancer cells. Conclusions: The current study indicates USP18 was an oncogenic gene in cervical cancer. Our findings not only deepened the understanding the biological function of USP18 in the pathogenesis of cervical cancer but also provided novel insight for cervical cancer therapy. Trial registration: retrospectively registered.

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Section: Discussionmentioning

confidence: 61%

USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway

Diao

Guo

Zhu

et al. 2020

Preprint

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“…In addition, it also plays an oncogenic role. 29,30 In the present study we attempted to prove that cell proliferation, migration, and invasion facilitated by DGCR8/ZFAT-AS1 in vitro might be ascribed to PRC2-induced H3K27me3 modification in the CDX2 promoter region. Additionally, we aimed to elucidate whether DGCR8 and ZFAT-AS1 played an important role in the progression of glioma.…”

Section: Introductionmentioning

confidence: 97%

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

Zhang

Ruan

et al. 2020

Molecular Therapy

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Studies have found that RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are dysregulated and play an important regulatory role in the development of tumors. Based on The Cancer Genome Atlas (TCGA) database, our findings from experiments, and the evidence of previous studies, we screened DiGeorge syndrome critical region gene 8 (DGCR8), ZFAT antisense RNA 1 (ZFAT-AS1), and caudal type homeobox 2 (CDX2) as research candidates. In the present study, DGCR8 and CDX2 were highly expressed and ZFAT-AS1 was markedly downregulated in glioma tissues and cells. DGCR8 or CDX2 knockdown or ZFAT-AS1 overexpression suppressed glioma cell proliferation, migration, and invasion and facilitated apoptosis. DGCR8 might decrease ZFAT-AS1 expression by attenuating its stability in a manner of inducing its cleavage. Importantly, ZFAT-AS1 could inhibit CDX2 transcription by mediating the methylation of histone H3 on lysine 27 (H3K27me3) modification induced by PRC2 in the CDX2 promoter region. In addition, CDX2 transcriptionally activated DGCR8 expression by binding to its promoter regions, forming a positive feedback loop of DGCR8/ZFAT-AS1/ CDX2. In conclusion, DGCR8/ZFAT-AS1 promotes CDX2 transcription in a PRC2 complex-dependent manner to facilitate the malignant biological behavior of glioma cells.

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“…Epithelial-mesenchymal transition (EMT) is one of the main causes of cancer metastasis 29 . EMT-activated transcription factors are invasive and motility characteristics for cervical cancer 30…”

Section: The Association Of Otud5 Expression With Clinicopathologic Cmentioning

confidence: 99%

“…2H). In cervical cancer, activation of PI3K-AKT signaling is closely related to tumor progression and poor prognosis30 . Consistently, OTUD5 is also downregulated in PI3K-AKT related subtypes(FIG.…”

mentioning

confidence: 99%

Peer Review #1 of "Analysis of deubiquitinase OTUD5 as a biomarker and therapeutic target for cervical cancer by bioinformatic analysis (v0.1)"

2020

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OTU deubiquitinase 5 (OTUD5), as a member of the ovarian tumor protease (OTU) family, was previously reported to play important roles in DNA repair and immunity. However, little is known about its function in tumors. Cervical cancer is a malignant tumor that seriously endangers the lives of women. Here, we found that low expression of OTUD5 in cervical cancer is associated with poor prognosis. Its expression is associated with tumor stage, metastatic nodes and tumor subtypes such as those related to the phosphatidylinositol-3-kinase (PI3K)-AKT signaling, epithelial-mesenchymal transition (EMT) and hormones. In addtion, we analyzed the coexpressed genes, related miRNAs, transcription factors, kinases, E3s and interacting proteins of OTUD5. We demonstrated that OTUD5 affects the expression levels of WD repeat domain 45 (WDR45), ubiquitinspecific peptidase 11 (USP11), GRIP1 associated protein 1 (GRIPAP1) and RNA binding motif protein 10 (RBM10). Moreover, hsa-mir-137, hsa-mir-1913, hsa-mir-937, hsa-mir-607, hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5. Furthermore, we performed enrichment analysis of 22 coexpressed genes, 33 related miRNAs and 30 interacting proteins. In addition to ubiquitination and immunology related processes, they also participate in Hippo signaling, insulin signaling, EMT, histone methylation and phosphorylation kinase binding. Our study for the first time analyzed the expression of OTUD5 in cervical cancer and its relationship with clinicopathology and provided new insights for further study of its regulatory mechanism in tumors.

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p53R2 overexpression in cervical cancer promotes AKT signaling and EMT, and is correlated with tumor progression, metastasis and poor prognosis

Cited by 18 publications

References 45 publications

USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway

USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

Peer Review #1 of "Analysis of deubiquitinase OTUD5 as a biomarker and therapeutic target for cervical cancer by bioinformatic analysis (v0.1)"

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