NF‐κB p65 promotes ovarian cancer cell proliferation and migration via regulating mortalin

Li, Shan; Lv, Mingqi; Qiu, Shi; Meng, Jiaqi; Liu, Wen; Zuo, Jiane; Yang, Ling

doi:10.1111/jcmm.14325

Cited by 31 publications

(23 citation statements)

References 51 publications

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“…Furthermore, we observed that miR-630 carried by EVs targeted the KLF6 expression in NFs, whereas over-expression of KLF6 could reverse the EVs-induced CAF activation and NF migration. Meanwhile, KLF6 can transactivate multiple genes that negatively regulate the NF-κB pathway, while activation of the NF-κB pathway was reported to accelerate the migration and invasion of OC cells ( Li et al, 2018 , 2019 ; Zheng et al, 2018 ). Accordingly, we documented that EVs activated the NF-κB pathway via the miR-630/KLF6 axis during CAF activation.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

Cui

Wang

Xie

2021

Front. Cell Dev. Biol.

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Ovarian cancer (OC) is a lethal gynecological malignancy. Extracellular vesicles (EVs) are crucial media in cell-to-cell communication by carrying microRNAs (miRs). The current study aims to investigate the underlying mechanism of miR-630 carried by OC cell-derived EVs in regard to invasion and metastasis of OC cells. miRs related to OC metastasis were searched and screened. The expression patterns of screened miRs in human normal fibroblasts (NFs) and carcinoma-associated fibroblasts (CAFs) were detected using RT-qPCR. miR-630 related to OC metastasis and CAFs activation was analyzed further. The levels of FAP and α-SMA were detected using Western blotting and immunofluorescence. The migration of NFs was measured using Transwell assay. OC cell-derived EVs were isolated and identified. Uptake of EVs by NFs was observed using immunofluorescence staining. The culture supernatant of NFs was collected and used to culture the low metastasis cell line OVCAR8. The migration and invasion of OC cells and epithelial mesenchymal transition (EMT) were measured. Moreover, a xenograft model was established by injecting OVCAR8 cells of different groups into nude mice. Lastly, the effect of EV-pretreated NFs on invasion and metastasis of OC cells was observed in vivo. miR-630 was upregulated in OC cells and CAFs, and further associated with CAF activation and OC metastasis. miR-630 overexpression increased the levels of FAP and α-SMA in NFs, resulting in the transformation of NFs into CAFs. EVs carried miR-630 into NFs and EVs promoted CAF activation. miR-630 targeted KLF6. miR-630 inhibition or KLF6 overexpression attenuated EVs-induced CAF activation. EVs activated the NF-κB pathway via the miR-630/KLF6 axis. The conditioned medium of NFs pretreated with EVs promoted the invasion and metastasis of OVCAR8 cells, while downregulating miR-630 in EVs partially inhibited the promotive effect of NFs. EV-pretreated NFs promoted invasion and metastasis of OC in vivo. In conclusion, EVs carried miR-630 into NFs, thereby facilitating CAF activation and promoting invasion and metastasis of OC by inhibiting KLF6 and activating the NF-κB pathway. Our findings might offer a novel mechanism of invasion and metastasis of OC from the perspective of tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

Cui

Wang

Xie

2021

Front. Cell Dev. Biol.

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“…NF-κB p65 was reported to promote cell proliferation, invasion and migration in ovarian cancer [ 18 , 19 ]. To investigate whether NOX4 regulates expression of NF-κB p65, cells were transfected with either lentivirus carrying shNOX4 or control shNC, total proteins were extracted for Western blotting to analyze NF-κB p65 protein levels.…”

Section: Resultsmentioning

confidence: 99%

NOX4 Signaling Mediates Cancer Development and Therapeutic Resistance through HER3 in Ovarian Cancer Cells

Liu

Huang

Wang

et al. 2021

Cells

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Development of resistance to therapy in ovarian cancer is a major hinderance for therapeutic efficacy; however, new mechanisms of the resistance remain to be elucidated. NADPH oxidase 4 (NOX4) is responsible for higher NADPH activity to increase reactive oxygen species (ROS) production. In this study, we showed that higher levels of NOX4 were detected in a large portion of human ovarian cancer samples. To understand the molecular mechanism of the NOX4 upregulation, we showed that NOX4 expression was induced by HIF-1α and growth factor such as IGF-1. Furthermore, our results indicated that NOX4 played a pivotal role in chemotherapy and radiotherapy resistance in ovarian cancer cells. We also demonstrated that NOX4 knockdown increased sensitivity of targeted therapy and radiotherapy through decreased expression of HER3 (ERBB3) and NF-κB p65. Taken together, we identified a new HIF-1α/NOX4 signal pathway which induced drug and radiation resistance in ovarian cancer. The finding may provide a new option to overcome the therapeutic resistance of ovarian cancer in the future.

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“…The NF-κB pathway, especially its important member P65, has a complicated relationship with cancer [ 25 , 26 , 27 , 28 ]. Shan et al demonstrated that P65 binds to the mortalin promoter and promotes ovarian cancer cell proliferation and migration via regulating mortalin [ 26 ]. Zhang et al showed that it can directly bind to the promoter of cyclin D1, mediating an increase in the protein’s expression [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human Gastric Cancer

Jiang

Zhao

et al. 2021

Biomolecules

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A Disintegrin and Metalloproteinase with Thrombospondin motifs 19 (ADAMTS19) has been reported to participate in the pathogenesis of solid cancers. However, its role in gastric cancer (GC) remains undocumented. Using immunohistochemistry (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR) on GC tissues and adjacent normal tissues, we found that ADAMTS19 was downregulated in GC tissues (IHC: p < 0.001; qRT-PCR: p = 0.017). Further investigation revealed that ADAMTS19 correlated with distant metastasis (p = 0.008) and perineural invasion (p = 0.018) and that patients with low ADAMTS19 had worse overall survival (p = 0.021). Gain- and loss-of-function assays showed that ADAMTS19 suppressed cell migration and invasion in vitro. Using bioinformatics analysis and co-immunoprecipitation, immunofluorescence, and dual-luciferase reporter gene assays, we confirmed that ADAMTS19 binds with cytoplasm P65, decreasing the nucleus phosphorylation of P65, a crucial transcription factor in the nuclear factor kappa-B (NF-κB) pathway, thereby downregulating S100 calcium-binding protein A16 (S100A16) expression. S100A16 acted as the downstream of ADAMTS19, reversing the suppression of cell migration and invasion by ADAMTS19 in vitro. A combination of ADAMTS19 and S100A16 expression provided the optimal prognostic indicator for GC. Patients with ADAMTS19high-S100A16low had better overall survival than ADAMTS19low-S100A16high patients (p = 0.006). These results suggest that ADAMTS19 suppresses cell migration and invasion by targeting S100A16 via the NF-κB pathway and that ADAMTS19 and S100A16 are potential metastasis and survival biomarkers for GC.

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NF‐κB p65 promotes ovarian cancer cell proliferation and migration via regulating mortalin

Cited by 31 publications

References 51 publications

RETRACTED: Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

RETRACTED: Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

NOX4 Signaling Mediates Cancer Development and Therapeutic Resistance through HER3 in Ovarian Cancer Cells

ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human Gastric Cancer

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