MFAP5 suppression inhibits migration/invasion, regulates cell cycle and induces apoptosis via promoting ROS production in cervical cancer

Li, Qingmei; Zhang, Yanqin; Jiang, Qiuli

doi:10.1016/j.bbrc.2018.10.146

Cited by 25 publications

(20 citation statements)

References 30 publications

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“…It has been widely reported that the biological function of NOX1 is to produce ROS (25)(26)(27), and ROS is found to regulate the metastasis through extracellular signal-regulated kinase (ERK) signaling pathway and EMT in a variety of tumors (28)(29)(30). In cervical cancer, ROS can promote cervical cancer metastasis through the β-catenin-WNT signaling pathway (31) and EMT (32). We assumed that DDX19A promotes the expression of NOX1 increases the production of ROS.…”

Section: Ddx19a Regulates Nox1 Expression and Enhances Reactive Oxygen Species Production In Cervical Squamous Cell Carcinomamentioning

confidence: 99%

DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production

Jiang

Wang

et al. 2021

Front. Oncol.

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The major obstacle to treat cervical squamous cell carcinoma (CSCC) is the high prevalence of metastasis, which severely affects 5-year survival rate and quality of life for cancer patients. The DEAD-box helicase family has been reported to be a critical mediator in the development and metastasis of various cancers. DEAD-box helicase 19A (DDX19A) is a member of the DEAD-box helicase family; however, its functional role in CSCC is unclear. In this study, bioinformatics analysis of clinical samples from public databases demonstrated that the expression of DDX19A was elevated in CSCC tissues and that high expression of DDX19A was positively correlated with metastasis and poor clinical outcome. Functionally, we found that DDX19A promoted CSCC cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, overexpression of DDX19A increased NADPH oxidase 1 (NOX1) expression, enhanced reactive oxygen species (ROS) production, and induced the migration and invasion of CSCC cells. Rescue experiments revealed that DDX19A-induced CSCC functional alterations were dependent on NOX1 and that DDX19A-promoted CSCC metastasis was abrogated upon the inhibition of ROS. Our results demonstrated that DDX19A could promote CSCC metastasis by inducing NOX1-mediated ROS production and that blockage of the NOX1/ROS axis might serve as a potential therapeutic target for patients with DDX19A-overexpressed CSCC.

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Section: Ddx19a Regulates Nox1 Expression and Enhances Reactive Oxygen Species Production In Cervical Squamous Cell Carcinomamentioning

confidence: 99%

DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production

Jiang

Wang

et al. 2021

Front. Oncol.

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“…Previous studies showed that MFAP5 inhibition induces G2/M phase arrest, decreases the expression of Cyclin B1, Cyclin D1, and CDK4, and enhances p21 and p53 levels in cervical cancer. Inhibition of cell growth by MFAP5 knockdown is dependent on reactive oxygen species (ROS) production [27]. In our study, we showed that MFAP5 promotes ICC G0/G1 to S-phase cell cycle transition which is dependent on Notch1 signaling activation.…”

Section: Discussionmentioning

confidence: 76%

MFAP5 facilitates the aggressiveness of intrahepatic Cholangiocarcinoma by activating the Notch1 signaling pathway

Zhu

et al. 2019

J Exp Clin Cancer Res

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BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. The dismal outcome of ICC patients is due to lack of early diagnosis, the aggressive biological behavior of ICC and the lack of effective therapeutic options. Early diagnosis and prognosis of ICC by non-invasive methods would be helpful in providing valuable information and developing effective treatment strategies.MethodsExpression of microfibrillar-associated protein 5 (MFAP5) in the serum of ICC patients was detected by ELISA. Human ICC specimens were immunostained by MFAP5 antibodies. The growth rate of human ICC cell lines treated with MFAP5 or MFAP5 shRNAs was examined by CCK8 and colony formation assays. Cell cycle analysis was performed with PI staining. The effect of MFAP5 inhibition was assessed by xenograft models in nude mice. RNA-seq and ATAC-seq analyses were used to dissect the molecular mechanism by which MFAP5 promoted ICC aggressiveness.ResultsWe identified MFAP5 as a biomarker for the diagnosis and prognosis of ICC. Upregulated MFAP5 is a common feature in aggressive ICC patients’ tissues. Importantly, MFAP5 level in the serum of ICC patients and healthy individuals showed significant differential expression profiles. Furthermore, we showed that MFAP5 promoted ICC cell growth and G1 to S-phase transition. Using RNA-seq expression and ATAC-seq chromatin accessibility profiling of ICC cells with suppressed MFAP5 secretion, we showed that MFAP5 regulated the expression of genes involved in the Notch1 signaling pathway. Furthermore, FLI-06, a Notch signaling inhibitor, completely abolished the MFAP5-dependent transcriptional programs.ConclusionsRaised MFAP5 serum level is useful for differentiating ICC patients from healthy individuals, and could be helpful in ICC diagnosis, prognosis and therapies.

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“…33 In addition, increasing evidence has revealed that the augmentation of ROS production is beneficial for the migration of tumours. 34,35 Other studies have found that ROS use multiple mechanisms to affect the initiation, growth, and spread of cancer and may promote or suppress cancer development, 36 suggesting they act as a "double-edged sword." As NOX2 is a known source of ROS production, we investigated the effect of ALO treatment on NOX2 expression in GC cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2–ROS-Mediated Pro-Survival Signal Pathways</p>

Wang¹,

Tang²,

Wang³

et al. 2020

DDDT

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Background: Aloin has been reported to have many pharmacological effects including antiinflammatory, anti-oxidant and anti-tumour activities. However, the precise molecular mechanisms underlying the anti-tumour properties of aloin are yet to be elucidated. Methods: HGC-27 and BGC-823 gastric cancer cells were treated with aloin. EdU and colony formation assays were used to detect the proliferation ability of cells. The migration of cells was detected using wound healing and transwell assays. Western blotting was used to detect the levels of cyclinD1, cyclin E1, MMPs, N-cadherin, E-cadherin and NOX2. The phosphorylation of Akt, mTOR, P70S6K, S6, Src, stat3 and IκBα were also detected by Western blotting. Flow cytometry was used to detect the cell cycle distribution.The location of p65 in cells was determined by using a confocal microscopy assay. The total amounts of ROS present in cells were measured using an ROS assay kit. Results: Here, we found that aloin inhibited the proliferation and migration of HGC-27 and BGC-823 gastric cancer cells using a combination of EdU, colony formation, wound healing and transwell assays. Further investigations revealed that aloin decreased the protein expression levels of cyclin D1, N-cadherin, and the matrix metalloproteinases (MMP)-2 and MMP-9; increased E-cadherin expression in a dose-dependent manner; inhibited reactive oxygen species (ROS) generation; and mediated the activation of Akt-mTOR, signal transducer and activator of transcription-3 (Stat3), and NF-κB signalling pathways. Our results also indicated that aloin is able to attenuate the expression levels of the two regulatory proteins of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), p47 phox and p22 phox , but had no effect on the level of gp91 phox. N-acetylcysteine treatment of gastric cancer cells inhibited ROS production and Akt-mTOR, Stat3, and IκBα phosphorylation. Taken together, our data suggest that aloin inhibits the proliferation and migration of gastric cancer cells by downregulating NOX2-ROS-mediated activation of the Akt-mTOR, Stat3, and NF-κB signalling pathways. Conclusion: Our findings suggest a potential role for aloin in the prevention of gastric cancer cell proliferation and migration and provide novel insights into the anti-cancer properties of aloin.

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MFAP5 suppression inhibits migration/invasion, regulates cell cycle and induces apoptosis via promoting ROS production in cervical cancer

Cited by 25 publications

References 30 publications

DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production

DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production

MFAP5 facilitates the aggressiveness of intrahepatic Cholangiocarcinoma by activating the Notch1 signaling pathway

<p>Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2–ROS-Mediated Pro-Survival Signal Pathways</p>

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