lncRNA PLAC2 activated by H3K27 acetylation promotes cell proliferation and invasion via the activation of Wnt/β‑catenin pathway in oral squamous cell carcinoma

Chen, Fubo; Qi, Shengcai; Zhang, Xu; Wu, Jinjin; Yang, Xi; Wang, Raorao

doi:10.3892/ijo.2019.4707

Cited by 55 publications

(72 citation statements)

References 46 publications

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“…The elevated expression of PLAC2 in tongue carcinoma cells resulted from the enrichment of its promoter region in H3K27 acetylation, which was dependent on CBP acetyltransferase activity. PLAC2 knockdown also diminished cell proliferation and migration [83]. The overexpression of UCA1 in laryngeal cancer cells was associated with reduced GSK-3β phosphorylation and elevated β-catenin level.…”

Section: The Role Of Epigenetic Mechanisms In Wnt/β-catenin Pathway Amentioning

confidence: 88%

“…Moreover, several long non-coding RNA molecules were also implicated in the regulation of Wnt signaling. The upregulation of MINCR, PLAC2 and UCA1 was frequently observed in head and neck cancers, and functionally, it promoted malignant progression by the activation of Wnt/β-catenin pathway [82][83][84]. The level of MINCR expression correlated with lymph node metastasis and shorter survival of OSCC patients.…”

Section: The Role Of Epigenetic Mechanisms In Wnt/β-catenin Pathway Amentioning

confidence: 91%

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The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

Paluszczak

2020

Cells

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The knowledge about the molecular alterations which are found in head and neck squamous cell carcinomas (HNSCC) has much increased in recent years. However, we are still awaiting the translation of this knowledge to new diagnostic and therapeutic options. Among the many molecular changes that are detected in head and neck cancer, the abnormalities in several signaling pathways, which regulate cell proliferation, cell death and stemness, seem to be especially promising with regard to the development of targeted therapies. Canonical Wnt signaling is a pathway engaged in the formation of head and neck tissues, however it is not active in adult somatic mucosal cells. The aim of this review paper is to bring together significant data related to the current knowledge on the mechanisms and functional significance of the dysregulation of the Wnt/β-catenin pathway in head and neck tumors. Research evidence related to the role of Wnt signaling activation in the stimulation of cell proliferation, migration and inhibition of apoptosis in HNSCC is presented. Moreover, its role in promoting stemness traits in head and neck cancer stem-like cells is described. Evidence corroborating the hypothesis that the Wnt signaling pathway is a very promising target of novel therapeutic interventions in HNSCC is also discussed.Cells 2020, 9, 723 2 of 20 blocking the interaction between PD-1 receptor and PD-L1, may be beneficial in patients with advanced, metastatic or recurrent HNSCC [7]. However, other therapeutic options are also necessary for the better clinical management of HNSCC patients. To that end, molecular alterations observed in HNSCC need to be studied in detail, in order to point to promising drug targets. Mechanisms of Wnt/β-Catenin Pathway Activation in HNSCCRecent genomic analyses have shown the prevalence of genetic driver alterations in HNSCC, which most frequently affect genes associated with receptor tyrosine kinase (e.g., EGFR, MET, KIT), PI3K, p53, Notch or Hippo signaling pathways. On the other hand, genetic alterations in genes related to canonical Wnt signaling were rarely detected in HNSCC [8,9]. In contrast to colorectal cancers, which show molecular alterations driving Wnt signaling activation in around 90% of cases [9], HNSCC were shown to lack CTNNB1 mutations and APC mutations were present infrequently [10][11][12][13][14][15][16]. The mutations of FAT1 tumor suppressor, which encodes a protocadherin protein that binds and inactivates β-catenin, were detected in some cases of HNSCC [17]. However, the activation of the Wnt/β-catenin pathway in HNSCC seems to be more prevalent than it is suggested by genetic findings, due to cross-talk with other molecular alterations, which can lead to pathway cross-activation. Indeed, it has been shown that β-catenin can be activated via enhanced EGFR or PI3K signaling, which belong to the most frequently dysregulated signaling pathways in HNSCC. In this regard, elevated EGFR expression was associated with delocalized β-catenin expression [13]. In another study, the nuclear ...

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Section: The Role Of Epigenetic Mechanisms In Wnt/β-catenin Pathway Amentioning

confidence: 88%

Section: The Role Of Epigenetic Mechanisms In Wnt/β-catenin Pathway Amentioning

confidence: 91%

The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

Paluszczak

2020

Cells

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“…Hypoxia is one of the important hallmarks of tumor microenvironment. Increasing studies have revealed that tumor hypoxia is closely related to the progression of cancer, such as tumor metastasis, recurrence and drug resistance [25][26][27][28]. It has been con rmed that hypoxia in vivo is associated with poor prognosis and high mortality in ovarian cancer patients, and involved in ovarian cancer cell proliferation [29,30].…”

Section: Discussionmentioning

confidence: 99%

miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6

Zhang

Tian

et al. 2020

Preprint

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Background The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear. Methods The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis. Results miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression. Conclusion Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer.

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“…The upregulated EP300/CBP mutations may attenuate differentiation to enable the establishment of HNSCC cell cultures (Martin et al, ). H3K27ac enrichment at the promoter region of long non‐coding RNA placenta‐specific protein 2 (PLAC2) gene is shown in OSCC, while CBP depletion reduced H3K27ac and PLAC2 levels (Chen et al, ). ERK1/2 phosphorylation suppressed by melatonin reduced p300/CBP level, decreased histone acetylation, then dampened matrix metalloproteinase‐9 transcription, and decreased cell migration (Yeh et al, ).…”

Section: Histone Modifications In Osccmentioning

confidence: 99%

Histone modifications in oral squamous cell carcinoma and oral potentially malignant disorders

et al. 2019

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Oral squamous cell carcinoma (OSCC) is a common malignancy with dismal prognosis without effective therapeutic options in advanced cases. The evolution from oral potentially malignant disorders to OSCC has poorly described underlying epigenetic features. With the ability of silencing or activation of vital genes, histone modifications’ and modifiers’ potentiality for early diagnosis, prognosis predicting, and therapy in OSCC were evaluated by extensive epigenetic studies. This review investigates the roles of dysregulated histone modifications and the associated modifying enzymes in OSCC onset and progression. Also, we focus on the current advances of histone modifications as therapeutic targets and the potential value of epi‐drugs.

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lncRNA PLAC2 activated by H3K27 acetylation promotes cell proliferation and invasion via the activation of Wnt/β‑catenin pathway in oral squamous cell carcinoma

Cited by 55 publications

References 46 publications

The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6

Histone modifications in oral squamous cell carcinoma and oral potentially malignant disorders

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