Overexpression of FER1L4 promotes the apoptosis and suppresses epithelial-mesenchymal transition and stemness markers via activating PI3K/AKT signaling pathway in osteosarcoma cells

Ma, Lifeng; Zhang, Liang; Ai, Guo; Liu, Lijun C.; Yu, Fei; Diao, Naicheng; Xu, Chongyang; Wang, Difan

doi:10.1016/j.prp.2019.04.004

Cited by 25 publications

(19 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In humans, the long non-coding RNA Fer1L4 plays a role in signaling, controlling cell proliferation, migration and apoptosis. The results of the vast majority of the studies are consistent with a function of Fer1L4 as a tumor suppressor in multiple types of cancer [32,[66][67][68]160,161]. The exception is a report about the Fer1L4 possible role in glioma progression, where high expression of Fer1L4 was associated with a poor disease prognosis [162].…”

Section: Fer1l4-a Non-muscle Ferlin Long Non-coding Rnamentioning

confidence: 53%

Functions of Vertebrate Ferlins

Bulankina

Thoms

2020

Cells

View full text Add to dashboard Cite

Ferlins are multiple-C2-domain proteins involved in Ca2+-triggered membrane dynamics within the secretory, endocytic and lysosomal pathways. In bony vertebrates there are six ferlin genes encoding, in humans, dysferlin, otoferlin, myoferlin, Fer1L5 and 6 and the long noncoding RNA Fer1L4. Mutations in DYSF (dysferlin) can cause a range of muscle diseases with various clinical manifestations collectively known as dysferlinopathies, including limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. A mutation in MYOF (myoferlin) was linked to a muscular dystrophy accompanied by cardiomyopathy. Mutations in OTOF (otoferlin) can be the cause of nonsyndromic deafness DFNB9. Dysregulated expression of any human ferlin may be associated with development of cancer. This review provides a detailed description of functions of the vertebrate ferlins with a focus on muscle ferlins and discusses the mechanisms leading to disease development.

show abstract

Section: Fer1l4-a Non-muscle Ferlin Long Non-coding Rnamentioning

confidence: 53%

Functions of Vertebrate Ferlins

Bulankina

Thoms

2020

Cells

View full text Add to dashboard Cite

show abstract

“…6a). Numerous studies have reported that the PI3K/AKT pathway plays an important role in metastasis through the regulation of EMT [23][24][25]. Therefore, the PI3K inhibitor LY294002 [26][27][28][29] was used to detect the effect of the PI3K/AKT pathway on AGK-induced RCC proliferation and metastasis.…”

Section: Agk Promotes Rcc Proliferation and Metastasis Via The Pi3k/amentioning

confidence: 99%

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Zhu

Zhong

et al. 2020

J Hematol Oncol

View full text Add to dashboard Cite

Background: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. Methods: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. Results: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. Conclusions: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

show abstract

“…Recently, it was suggested that long non-coding RNA Fer1L4 negatively controlled proliferation and migration of lung cancer cells, probably through the PI3K/AKT pathway [117]. The same observation was made in osteosarcoma cells [118], esophageal squamous cell carcinoma [119], and hepatocellular carcinoma [120].…”

Section: Ferlins In Cancer Potential Targets To Kill Cancermentioning

confidence: 79%

Ferlin Overview: From Membrane to Cancer Biology

Peulen

Rademaker

Anania

et al. 2019

Cells

View full text Add to dashboard Cite

In mammal myocytes, endothelial cells and inner ear cells, ferlins are proteins involved in membrane processes such as fusion, recycling, endo- and exocytosis. They harbour several C2 domains allowing their interaction with phospholipids. The expression of several Ferlin genes was described as altered in several tumoural tissues. Intriguingly, beyond a simple alteration, myoferlin, otoferlin and Fer1L4 expressions were negatively correlated with patient survival in some cancer types. Therefore, it can be assumed that membrane biology is of extreme importance for cell survival and signalling, making Ferlin proteins core machinery indispensable for cancer cell adaptation to hostile environments. The evidences suggest that myoferlin, when overexpressed, enhances cancer cell proliferation, migration and metabolism by affecting various aspects of membrane biology. Targeting myoferlin using pharmacological compounds, gene transfer technology, or interfering RNA is now considered as an emerging therapeutic strategy.

show abstract

Overexpression of FER1L4 promotes the apoptosis and suppresses epithelial-mesenchymal transition and stemness markers via activating PI3K/AKT signaling pathway in osteosarcoma cells

Cited by 25 publications

References 25 publications

Functions of Vertebrate Ferlins

Functions of Vertebrate Ferlins

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Ferlin Overview: From Membrane to Cancer Biology

Contact Info

Product

Resources

About