RE: P16 INK41 promoter hypermethylation is associated with invasiveness and prognosis of oral squamous cell carcinoma in an age dependent manner. Su et al. Oral Oncology 46 (2010) 734–739

One way of trying to control oral squamous cell carcinoma is to invest in new therapies focused on the molecular biology of receptors and their intracellular signaling pathways. This study aimed to evaluate the effect of LY2109761 (an inhibitor of TGF-β receptors) on cell migration in oral squamous cell carcinoma in vitro. Actin cytoskeleton of SCC-4 cells control and LY2109761 (1, 5 and 10 μM) treated on three-dimensional Matrigel were analysed by using confocal laser microscopy. Control and LY2109761 (1, 5 and 10 μM) treated cells that migrated through the membrane of three-dimensional cell migration assays were counted, significance was p<0.05. Control cells were seen with voluminous cytoplasm, cell cortex preserved and actin cytoskeleton well developed with well distributed actin filaments. Regardless of concentration, cells treated showed: rounded morphology and small size, scanty cytoplasm, cortical F-actin less clear that the control cells, and disruption of actin filaments. The migratory cells were inhibited by treatment with LY2109761 [F (3, 11) = 3742, p<0.0001], in a dose-dependent manner. These results suggest that LY2109761 exerts an inhibitory effect on the actin cytoskeleton and cell migration on SCC-4 cells, therefore, it is a promising therapeutic option for oral squamous cell carcinoma.

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METTL3 Promotes Oral Squamous Cell Carcinoma Progression by Enhancing SLC7A11 mRNA Stability via m6A-Mediated IGF2BP2 Binding

10.21203/rs.3.rs-242092/v1 ◽

2021 ◽

Author(s):

Le Xu ◽

Qingxiang Li ◽

Yifei Wang ◽

Lin Wang ◽

Yuxing Guo ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Mrna Stability ◽

Messenger Rna ◽

Specific Treatment ◽

Dependent Manner ◽

Rna Seq

Abstract Background: As the key enzyme of the N6-methyladenosine (m6A) in eukaryotic messenger RNA, METTL3 plays important roles in tumor progression, but the exact mechanism by which METTL3 controls oral squamous cell carcinoma (OSCC) progression remains unclear. Methods: METTL3 expression in OSCC samples was analyzed by qPCR and immunohistochemistry. The effects of METTL3 suppression on OSCC cell lines were measured by CCK-8, Ki-67 flow cytometry analysis, invasion transwell and wound healing assays. MeRIP-seq and RNA-seq analysis were performed to explore target gene of METTL3. RIP-qPCR and RNA stability assays were performed to explore the mechanism by which METTL3 regulated the target genes. Triptolide was used to evaluate its specific treatment effects on METTL3 in OSCC cells. BALB/c nude mice were used to establish orthotopic and subcutaneous xenograft models to verify the in vitro results.Results: METTL3 was upregulated in OSCC tissues than adjacent normal tissues, and its expression was associated with T stage, lymphatic metastasis and prognosis. In vitro and in vivo studies suggested that METTL3 suppression impaired cell proliferation, invasion, and migration. MeRIP-seq and RNA-seq analysis identified that SLC7A11 mRNA was the m6A target of METTL3, which was verified by meRIP-qPCR, qPCR and western blot. METTL3 depletion decreased the stability of SLC7A11 mRNA, and IGF2BP2 was involved in this process. Moreover, METTL3 knockdown attenuated the binding between SLC7A11 mRNA and IGF2BP2, finally leading to accelerate SLC7A11 mRNA degradation. Triptolide inhibited METTL3 and SLC7A11 expression in a dose-dependent manner, thus suppressing malignancy of OSCC cells. Conclusions: METTL3 enhances the mRNA stability of SLC7A11 via m6A-mediated binding of IGF2BP2, which thus promotes OSCC progression, and triptolide inhibits OSCC by suppressing METTL3-SLC7A11 axis.

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Tanshinone Suppresses Arecoline-Induced Epithelial‐Mesenchymal Transition in Oral Submucous Fibrosis by Epigenetically Reactivating the p53 Pathway

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x14941825760362 ◽

2018 ◽

Vol 26 (3) ◽

pp. 483-494 ◽

Cited By ~ 3

Author(s):

Lian Zheng ◽

Zhen-Jie Guan ◽

Wen-Ting Pan ◽

Tian-Feng Du ◽

Yu-Jia Zhai ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Salvia Miltiorrhiza ◽

Oral Submucous Fibrosis ◽

Precancerous Lesion ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Submucous Fibrosis

Oral submucous fibrosis (OSF) induced by chewing of the areca nut has been considered to be a precancerous lesion with a high probability of developing oral squamous cell carcinoma. Tanshinone (TSN) is the main component extracted from Salvia miltiorrhiza, a traditional Chinese medicine, which was found to have diverse pharmacological effects, such as anti-inflammatory and antitumor. In the current study, we aimed to identify the inhibitory effects and the underlying mechanism of TSN on OSF progress. We found that treatment with TSN inhibited the arecoline-mediated proliferation of primary human oral mucosal fibroblasts and reversed the promotive effects of arecoline on the EMT process. By RNA deep sequencing, we screened two possible targets for TSN: LSD1 and p53. We confirmed that p53 is much lower in OSF than in normal mucous tissues. In addition, p53 and its downstream molecules were decreased by arecoline treatment in oral mucosal fibroblasts, which was reversed by treatment with TSN in a dose-dependent manner. Our results also revealed that arecoline stimulation resulted in hypermethylation of the promoter of TP53 and subsequent downregulation of p53 levels, which was reversed by TSN. Furthermore, we identified that LSD1 could epigenetically activate TP53 by recruiting H3K27me1 and H3K4m2 to its promoter. Our findings provide new insights into the mechanism by which TSN influences arecoline-induced OSF and rationale for the development of clinical intervention strategies for OSF and even oral squamous cell carcinoma.

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The serum biomarker chemerin promotes tumorigenesis and metastasis in oral squamous cell carcinoma

Clinical Science ◽

10.1042/cs20181023 ◽

2019 ◽

Vol 133 (5) ◽

pp. 681-695 ◽

Cited By ~ 6

Author(s):

Zhiyuan Lu ◽

Jianfeng Liang ◽

Qianting He ◽

Quan Wan ◽

Jinsong Hou ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Migration And Invasion ◽

Tumour Resection ◽

Dependent Manner ◽

Small Interfering Rnas ◽

Malignant Tumours

AbstractChemerin, which is encoded by retinoic acid receptor responder 2 (RARRES2), has been found to be related to malignant tumours, but its role in the development of oral squamous cell carcinoma (OSCC) is largely unexplored. In the present study, a higher serum level of chemerin was evident in patients with OSCC than in healthy individuals, and this high level of chemerin significantly decreased after tumour resection. In addition, high chemerin levels were positively associated with advanced tumour stage and lymph node metastasis. The expression levels of chemerin and Chemerin Receptor 23 (ChemR23) were positively correlated with the migration and invasion of OSCC cell lines. Recombinant chemerin (R-chemerin) enhanced the in vitro migration, invasion and proliferation of OSCC cells in a concentration-dependent manner, and short hairpin RNAs (shRNAs) targeting RARRES2 decreased chemerin expression and inhibited OSCC cell metastasis and proliferation both in vitro and in vivo. Additionally, R-chemerin activated manganese superoxide dismutase (SOD2) and increased the amount of intracellular hydrogen peroxide (H2O2), leading to a significant decrease in E-cadherin expression and dramatic increase in the expression of phosphorylated ERK1/2 (p-ERK1/2), Slug, Vimentin and N-cadherin, but shRNAs targeting RARRES2 reversed these effects. Moreover, knockdown of ChemR23 with small interfering RNAs (siRNA) significantly inhibited chemerin-induced OSCC cell migration/invasion and SOD2 activity. Our results revealed that chemerin is a novel biomarker for OSCC. Chemerin/ChemR23 promotes tumorigenesis and metastasis in OSCC and may be a new therapeutic target for OSCC.

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Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1

International Journal of Molecular Sciences ◽

10.3390/ijms21186470 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6470

Author(s):

Yohan Seo ◽

Nguyen Hoang Anh ◽

Yunkyung Heo ◽

So-Hyeon Park ◽

Phan Van Kiem ◽

...

Keyword(s):

Prostate Cancer ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Viability ◽

Cell Carcinoma ◽

Squamous Cell ◽

Chloride Channel ◽

Dependent Manner ◽

Channel Activity ◽

Mallotus Apelta

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds (1 and 2) and four known compounds (3–6) from Mallotus apelta. These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells. Interestingly, compounds 1 and 2 significantly reduced both ANO1 channel activity and cell viability. Electrophysiological study revealed that compound 2 (Ani-D2) is a potent and selective ANO1 inhibitor, with an IC50 value of 2.64 μM. Ani-D2 had minimal effect on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity and intracellular calcium signaling. Notably, Ani-D2 significantly reduced ANO1 protein expression levels and cell viability in an ANO1-dependent manner in PC-3 and oral squamous cell carcinoma CAL-27 cells. In addition, Ani-D2 strongly reduced cell migration and induced activation of caspase-3 and cleavage of PARP in PC-3 and CAL-27 cells. This study revealed that a novel ANO1 inhibitor, Ani-D2, has therapeutic potential for the treatment of several cancers that overexpress ANO1, such as prostate cancer and oral squamous cell carcinoma.

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