Melatonin inhibits MLL-rearranged leukemia via RBFOX3/hTERT and NF-κB/COX-2 signaling pathways

Tang, Yan; Sun, Xi; Huang, Li; Liu, Xiao Jian; Qin, Ge; Wang, Li Na; Zhang, Xiao Li; Ke, Zhi Yong; Luo, Jie; Liang, Cong; Peng, Chun Jin; Tang, Wen; Liu, Yu; Huang, Wenlin; Li, Xue; Deng, Wuguo

doi:10.1016/j.canlet.2018.11.037

Cited by 24 publications

(19 citation statements)

References 34 publications

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“…Although RBFOX3 is an antigen of the neuronal marker antibody NeuN (35), it has been implicated in GC. Recent studies indicate that RBFOX3 regulates various physiological processes apart from being an alternative splicing factor (17,36). It binds DNA and regulates microRNA transcription (12,14).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: RBFOX3 Promotes Gastric Cancer Growth and Progression by Activating HTERT Signaling

et al. 2020

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Tumor invasion, metastasis, and recrudescence remain a considerable challenge in the treatment of gastric cancer (GC). Herein we first identified that RNA binding protein fox-1 homolog 3 (RBFOX3) was markedly overexpressed in GC tissues and negatively linked to the survival rate of GC patients. RBFOX3 promoted cell division and cell cycle progression in vitro and in vivo. Furthermore, RBFOX3 increased the cell invasion and migration ability. The suppression of GC cell multiplication and invasion, caused by silencing of RBFOX3, was rescued by HTERT overexpression. Additionally, RBFOX3 augmented the resistance of GC cells to 5-fluorouracil by repressing RBFOX3. Mechanistically, the exogenous up-regulation of RBFOX3 triggered promoter activity and HTERT expression, thereby enhancing the division and the development of GC cells. Further co-immunoprecipitation tests revealed that RBFOX3 bound to AP-2β to modulate HTERT expression. In conclusion, our study indicates that a high expression of RBFOX3 promotes GC progression and development and predicts worse prognosis. Collectively, these results indicate that the RBFOX3/AP-2β/HTERT signaling pathway can be therapeutically targeted to prevent and treat GC recurrence and metastasis.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: RBFOX3 Promotes Gastric Cancer Growth and Progression by Activating HTERT Signaling

et al. 2020

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“…31 Moreover, hTERT was found to induce thyroid cancer cell proliferation by regulating PTEN/AKT signalling pathway. 48 Considering that melatonin exerted its anti-tumour effects by inhibiting the expression of hTERT and the activity of telomerase, 49…”

Section: Discussionmentioning

confidence: 99%

Melatonin synergizes BRAF‐targeting agent dabrafenib for the treatment of anaplastic thyroid cancer by inhibiting AKT/hTERT signalling

Liao

Gao

Chang³

et al. 2020

J Cellular Molecular Medi

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As a selective inhibitor of BRAF kinase, dabrafenib has shown potent anti‐tumour activities in patients with BRAFV600E mutant anaplastic thyroid cancer. However, the resistance of thyroid cancer cells to dabrafenib limited its therapeutic effect. The effects of melatonin and dabrafenib as monotherapy or in combination on the proliferation, cell cycle arrest, apoptosis, migration and invasion of anaplastic thyroid cancer cells were examined. The molecular mechanism involved in drug combinations was also revealed. Melatonin enhanced dabrafenib‐mediated inhibition of cell proliferation, migration and invasion, and promoted dabrafenib‐induced apoptosis and cell cycle arrest in anaplastic thyroid cancer cells. Molecular mechanistic studies further uncovered that melatonin synergized with dabrafenib to inhibit AKT and EMT signalling pathways. Furthermore, melatonin and dabrafenib synergistically inhibited the expression of hTERT, and the inhibition of cell viability and the induction of cell cycle arrest mediated by the combination of these two drugs were reversed by hTERT overexpression. Taken together, our results demonstrated that melatonin synergized the anti‐tumour effect of dabrafenib in human anaplastic thyroid cancer cells by inhibiting multiple signalling pathways, and provided new insights in exploring the potential therapeutic targets for the treatment of anaplastic thyroid cancer.

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“…RBFOX3 is an antigen of the neuronal marker antibody NeuN [35] , which makes its involvement in GC surprising. Recent studies indicate that RBFOX3 has a wide range of physiological functions on top of its traditional role as a an alternative splicing factor [17,36] . RBFOX3 has been found to bind DNA in vitro and to control transcription of a subset of microRNAs [12,14] .…”

Section: Discussionmentioning

confidence: 99%

<strong>RBFOX3 Promotes Gastric Cancer Growth and Progression through Activating HTERT Signaling</strong>

Luo¹,

Zhu²,

Luo³

et al. 2020

Preprint

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Tumor invasion, metastasis, and recrudesce remain a considerable challenge in the treatment of gastric cancer (GC). Herein, we first identified that RBFOX3 (RNA binding protein fox-1 homolog 3) was significantly up-regulated in GC tissues and negatively linked to the survival rate of GC patients. RBFOX3 promoted cell division and cell cycle progression in vitro as well as in vivo. Furthermore, RBFOX3 increased cell invasion and migration ability. Interestingly, both the suppression of GC cell multiplication and invasion moderated by the silencing of RBFOX3 was rescued by HTERT up-regulation. Additionally, RBFOX3 augmented the resistance of GC cells to 5-fluorouracil (5-Fu) by repressing RBFOX3. Mechanistically, exogenous up-regulation of RBFOX3 triggered promoter activity and HTERT expression thereby enhancing the division and development of GC cells. Importantly, our findings revealed that RBFOX3 interacted with AP-2β to modulate the HTERT expression as demonstrated by co-immunoprecipitation analysis. In conclusion, our study indicates that high expression of RBFOX3 promotes GC progression and development but predicts worse prognosis by stimulating HTERT signaling. Moreover, the results suggest that the RBFOX3/AP-2β/HTERT pathway is a novel target for the development of therapeutic agents for the prevention and treatment of GC reappearance and metastasis.

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Melatonin inhibits MLL-rearranged leukemia via RBFOX3/hTERT and NF-κB/COX-2 signaling pathways

Cited by 24 publications

References 34 publications

RETRACTED: RBFOX3 Promotes Gastric Cancer Growth and Progression by Activating HTERT Signaling

RETRACTED: RBFOX3 Promotes Gastric Cancer Growth and Progression by Activating HTERT Signaling

Melatonin synergizes BRAF‐targeting agent dabrafenib for the treatment of anaplastic thyroid cancer by inhibiting AKT/hTERT signalling

<strong>RBFOX3 Promotes Gastric Cancer Growth and Progression through Activating HTERT Signaling</strong>

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