scholarly journals Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinfang Liu ◽  
Zijian Zhou ◽  
Ling Ma ◽  
Chujun Li ◽  
Yu Lin ◽  
...  

Abstract Background Melanoma is an extremely aggressive type of skin cancer and experiencing a expeditiously rising mortality in a current year. Exploring new potential prognostic biomarkers and therapeutic targets of melanoma are urgently needed. The ambition of this research was to identify genetic markers and assess prognostic performance of N6-methyladenosine (m6A) regulators in melanoma. Methods Gene expression data and corresponding clinical informations of melanoma patients as well as sequence data of normal controls are collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Quantitative real-time PCR (qRT-PCR) analysis was carried out to detect the RNA expression of IGF2BP3 in A375 cell line, melanoma tissues, and normal tissues. Western blot, cell proliferation, and migration assays were performed to assess the ability of IGF2BP3 in A375 cell line. Results Differently expressed m6A regulators between tumor samples and normal samples were analyzed. A three-gene prognostic signature including IGF2BP3, RBM15B, and METTL16 was constructed, and the risk score of this signature was identified to be an independent prognostic indicator for melanoma. In addition, IGF2BP3 was verified to promote melanoma cell proliferation and migration in vitro and associate with lymph node metastasis in clinical samples. Moreover, risk score and the expression of IGF2BP3 were positively associated with the infiltrating immune cells and these hub genes made excellent potential drug targets in melanoma. Conclusion We identified the genetic changes in m6A regulatory genes and constructed a three-gene risk signature with distinct prognostic value in melanoma. This research provided new insights into the epigenetic understanding of m6A regulators and novel therapeutic strategies in melanoma.

2018 ◽  
Vol 8 (6) ◽  
pp. 155-158
Author(s):  
Susmita Saha ◽  
Deepjyoti Bhattacharjee ◽  
Anwesha Saha ◽  
Gahin De ◽  
Partha Saha ◽  
...  

Earthworm, Eutyphoeus gammiei, homogenate (EGH) was screened for wound healing activity on human keratinocyte cell line, HaCat, by cell proliferation and migration assays. The maximum proliferation and migration of keratinocyte cells were observed at the dose of 25μg/ml. As cell proliferation and migration are key factors for wound healing, the study clearly suggests the potential role of earthworm species Eutyphoeus gammiei on wound healing. Keywords: Eutyphoeus gammiei, Keratinocyte, MTT assay, scratch assay.


2007 ◽  
Vol 14 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Frauke Döll ◽  
Josef Pfeilschifter ◽  
Andrea Huwiler

Sphingosine kinases (SK) catalyze the formation of sphingosine-1-phosphate (S1P) which plays a crucial role in cell growth and survival. Here, we show that prolactin (PRL) biphasically activates the SK-1, but not the SK-2 subtype, in the breast adenocarcinoma cell-line MCF7. A first peak occurs after minutes of stimulation and is followed by a second delayed activation after hours of stimulation. A similar biphasic effect on SK-1 activity is seen for 17β-estradiol (E2). The delayed activation of SK-1 derives from an upregulated mRNA and protein expression and is due to increased SK-1 promoter activity and mechanistically involves STAT5 activation as well as protein kinase C and the classical mitogen-activated protein kinases. Furthermore, glucocorticoids also block both hormone-induced SK-1 expression and activity. Functionally, long-term stimulation of MCF7 cells with PRL or E2 is well known to trigger increased cell proliferation and migration. Both hormone-induced cell responses critically involve SK-1 activation since the depletion of SK-1, but not SK-2, by siRNA transfection abolishes the hormone-induced cell proliferation and migration. In summary, our data show that PRL and E2 cause a pronounced delayed SK-1 activation which is due to increased gene transcription, and critically determines the capability of cells to grow and move. Thus, the SK-1 may represent a novel attractive target for anti-tumor therapy.


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