The role of YWHAZ in cancer: A maze of opportunities and challenges

Gan, Yun; Feng, Yun‐Zhi; He, Xingxing

doi:10.7150/jca.41316

Cited by 79 publications

(74 citation statements)

References 84 publications

(183 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…Among these genes, YWHAZ (14-3-3ζ) is a member of the 14-3-3 proteins and has multiple functions in various signal transduction pathways [ 39 ]. The overexpression of YWHAZ has been reported in a wide range of cancers, and its aberrant expression contributes to cancer progression and drug resistance [ 39 ]. In PDAC cells, tumor-associated macrophages invade cancer tissues after anticancer drug treatment, and the tumor-associated macrophage-secreted YWHAZ is shown to contribute to chemotherapy resistance [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Tanaka

Okada

Hozaka

et al. 2020

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, and its prognosis is abysmal; only 25% of patients survive one year, and 5% live for five years. MicroRNA (miRNA) signature analysis of PDAC revealed that both strands of pre-miR-30c (miR-30c-5p, guide strand; miR-30c-2-3p, passenger strand) were significantly downregulated, suggesting they function as tumor-suppressors in PDAC cells. Ectopic expression assays demonstrated that these miRNAs attenuated the aggressiveness of PDAC cells, e.g., cell proliferation, migration, and invasiveness. Through a combination of in silico analyses and gene expression data, we identified 216 genes as putative oncogenic targets of miR-30c-5p and miR-30c-2-3p regulation in PDAC cells. Among these, the expression of 18 genes significantly predicted the 5-year survival rates of PDAC patients (p < 0.01). Importantly, the expression levels of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were found to be independent prognostic factors for patient survival (p < 0.01). We focused on TOP2A (DNA Topoisomerase II Alpha) and investigated its potential as a therapeutic target for PDAC. The overexpression of TOP2A and its transcriptional activators (SP1 and HMGB2) was detected in PDAC clinical specimens. Moreover, the knockdown of TOP2A enhanced the sensitivity of PDAC cells to anticancer drugs. Our analyses of the PDAC miRNA signature and tumor-suppressive miRNAs provide important insights into the molecular pathogenesis of PDAC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Tanaka

Okada

Hozaka

et al. 2020

Cancers

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“…14-3-3zeta (also named YWHAZ) is a central hub protein for many signal transduction pathways [157]. Accumulating evidence demonstrates that it acts as an oncogene by targeting downstream protein kinases, apoptosis-associated proteins, and metastasis-related proteins in a wide range of cell activities including cell growth, cell cycle, apoptosis, migration, and invasion.…”

Section: The Interaction Of Tau With Proteins Linked To Cancermentioning

confidence: 99%

“…Accumulating evidence demonstrates that it acts as an oncogene by targeting downstream protein kinases, apoptosis-associated proteins, and metastasis-related proteins in a wide range of cell activities including cell growth, cell cycle, apoptosis, migration, and invasion. It is frequently up-regulated in cancer cells possibly requiring regulation by microRNAs or long noncoding RNAs [157]. Additionally, 14-3-3zeta has shown value as a biomarker for cancer diagnosis, prognosis and chemoresistance [157].…”

Section: The Interaction Of Tau With Proteins Linked To Cancermentioning

confidence: 99%

Tau: At the Interface Between Neurodegeneration and Cancer?

Papin¹,

Paganetti²

2020

Preprint

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For its microtubule-binding properties, the expression level of the neurodegeneration-associated protein Tau is pondered as a potential modifier of cancer resistance to chemotherapy since decades. Indeed, Tau binds microtubules at the same site as taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network in order to stall cell division and to induce tumor cell death. Whilst independent studies report the association between low Tau expression and superior taxane response, the data were refused by a meta-analysis, suggesting interference of other parameters. Unpredictably, Tau expression level was identified as a prognostic cancer marker, whereby its positive or negative predictive value for survival depended on the cancer type. With recent experimental evidence linking Tau to P53 signaling, DNA stability and protection and to the implication of Tau in cancer is strengthened. The identification of a role of Tau at the interface between two major aging-related disorder families, neurodegeneration and cancer, offers clues for the epidemiological observation inversely correlating these disorders. Elucidating how Tau is mechanistically implicated in cellular pathways common to these devastating illnesses may extend the Tau-targeting therapeutic opportunities to cancer.

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“…Tyrosine 3 monooxygenase/tryptophan 5-monooxygenase activation protein zeta, also named YWHAZ or 14-3-3ζ, is a key modulator on the β-catenin signaling pathway and is closely associated with tumorigenesis and cancer metastasis (13). YWHAZ has been shown to be overexpressed in multiple types of cancers and regulated by miRNAs or lncRNAs (14). Zeng Y et al reported that lncRNA LUCAT1/miR-134-5p/YWHAZ axis can promote proliferation and invasion of GC (15); Wang H et al found circ-SERPINE2/miR-375/YWHAZ axis promote proliferation (16) and Jin CX et al clari ed how YWHAZ effects apoptosis and autophagy in GC (17).…”

Section: Introductionmentioning

confidence: 99%

YY1-modulated Long Non-coding RNA SNHG12 Predicts and Promotes Gastric Cancer Metastasis via Activating miR-218-5p/YWHAZ-dependent β-catenin: A Bed to Bench Approach

Zhang¹,

Dai²,

Beeharry³

et al. 2020

Preprint

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Background: Gastric Cancer (GC) is one of the leading causes of cancer-related deaths and mortality. Long non-coding RNAs (lncRNAs) such as SNHG12 play important roles in the pathogenesis and progression of cancers. However, the role and significanve of SNHG12 in the metastasis of GC has not yet been thoroughly investigated.Methods: The SNHG12 expression pattern was detected in GC tissue samples from our faculty and cell lines using quantitative reverse transcription PCR. In vivo and in vitro gain and loss assays were conducted to observe the effects of SNHG12 regulation on GC cell metastasis potential. The underlying mechanisms of SNHG12 regulation on EMT and metastatic potential of GC cells were further determined by quantitative reverse transcription PCR, western blotting, dual luciferase reporter assays, co-immunoprecipitation, immunoprecipitation, RIP assays, TOPFlash/FOPFlash reporter assays and Ch-IP assays.Results: SNHG12 was upregulated in GC tissues and cell lines. The expression levels of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM staging and lymph node metastasis, and was associated with poorer DFS and OS in the GC patients. SNHG12 was significantly highly expressed in peritoneal metastatic tissues from GC patients and mice subjects, suggesting a possible role of SNHG12 in peritoneal carcinomatosis from GC. Further in vivo and in vitro gain and loss assays indicated that SNHG12 promoted GC metastasis and EMT. Based on hypothetical bioinformatic analysis findings, our mechanistic analyses revealed that miR-218-5p was a direct target of SNHG12 and suggested that both SNHG12 and miR-218-5p could collectively regulate YWHAZ, forming the SNHG12/ miR-218-5p/YWHAZ axis, hereby decreasing the ubiquitination of β-catenin, thus activating the β-catenin signaling pathway and facilitating metastasis and EMT. Further analysis also revealed that the transcription factor YY1 could negatively modulate SNHG12 transcription.Conclusions: Our findings demonstrate that SNHG12 is be a potential prognostic marker and therapeutic target for GC. Negatively modulated by transcription factor YYI, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and hence activating the β-catenin signaling pathway. Furthermore, we discovered high SNHG12 expression could be related to peritoneal carcinomatosis from GC but this requires further validation.

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The role of YWHAZ in cancer: A maze of opportunities and challenges

Cited by 79 publications

References 84 publications

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Tau: At the Interface Between Neurodegeneration and Cancer?

YY1-modulated Long Non-coding RNA SNHG12 Predicts and Promotes Gastric Cancer Metastasis via Activating miR-218-5p/YWHAZ-dependent β-catenin: A Bed to Bench Approach

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