ABSTRACT
So far, researchers have found more than one hundred different kinds of chemical modifications on RNA. Most of these modifications are distributed on high abundant non-coding RNAs and are important for maintaining the functions of these non-coding RNAs. In recent years, thanks to the application of high-resolution mass spectrometry and the development of whole-transcriptome sequencing technologies, more and more modifications on mRNA have been discovered, and accurately mapped and localized, including N
ABSTRACT
@#[Abstract] Objective: To investigate the effects of dyskerin pseudouridine synthase 1 (DKC1) on the proliferation, cell cycle and apoptosis of mucosal melanoma cells and its potential mechanisms. Methods: qPCR was used to detect the mRNA expression of DKC1 in mucosal melanoma cell lines HMV II, GAK and normal skin cell line BJ. HMV II and GAK cells were interfered with DKC1 siRNA (si-DKC1 group) and control siRNA(si-Ctrl group) respectively; 48 h later, qPCR and Western blotting were used to verify the interfer‐ence efficiency. CCK-8 assay was used to detect the effect of DKC1 knockdown on the proliferation of mucousal melanoma cells. Flow cytometry was used to detect the apoptosis and cell cycles. Western blotting and qPCR were used to detect the molecule expressions of related pathways. Results: The mRNA and protein expression levels of DKC1 in HMV II and GAK cells were significantly higher than those in BJ cells (all P<0.01). After 48 h of siRNA transfection, compared with the si-Ctrl group, the mRNA and protein levels of DKC1 in HMV II and GAK cells of the si-DKC1 group significantly reduced (all P<0.01), the cell proliferation level significantly re‐duced (P<0.05 or P<0.01), and the apoptosis rate of cells significantly increased (all P<0.01); in addition, the mRNA expressions of proapoptotic molecules caspase 9, BAK and PUMA increased significantly (P<0.05 or P<0.01) and the cell cycle was blocked (P<0.05 or P<0.01); moreover, the phosphorylation levels of MEK and ERK1/2 were significantly reduced (P<0.05). Conclusion: Knockdown of DKC1 can inhibit the proliferation of mucousal melanoma cells, promote cell cycle arrest and induce apoptosis, and its mechanism may be related to MEK/ERK signal pathway.
ABSTRACT
Messenger RNA (mRNA) can be modified by more than 100 chemical modifications. Among these modifications, N6-methyladenosine (m⁶A) is one of the most prevalent modifications. During the processes of cells differentiation, embryo development or stress, m⁶A can be modified on key mRNAs and regulate the progress of cells through modulating mRNA metabolism and translation. Other mRNA modifications, including N1-methyladenosine (m¹A), 5-methylcytosine (m⁵C) and pseudouridine, together with m⁶A form the epitranscriptome of mRNA that accurately modulate the mRNA translation. Here we review the types and characteristic of mRNA epigenetic modifications, especially the recent progresses of the function of m⁶A, we also expect the main research direction of m⁶A epigenetic modification in the future.
Subject(s)
Adenosine , Genetics , Metabolism , Cell Differentiation , Genetics , Embryonic Development , Genetics , Epigenesis, Genetic , Gene Expression Regulation , RNA Processing, Post-Transcriptional , RNA, Messenger , MetabolismABSTRACT
The urinary concentration of pseudouridine, primarily a degradation product of transfer ribonucleic acid, was determined by high-performance liquid chromatography in 84 patients with lung cancer, 22 patients with pulmonary infectious diseases and 69 healthy controls. The concentration of pseudouridine in the patient with lung cancer (33.46 ? 9.94nmol/ ?mol) was significantly higher than that in the paients with pulmonary infectious diseases (26.25 ? 4.17nmol/ ?mol, P