ABSTRACT
@#Epigenetic modification plays an important role in the biological regulatory process of eukaryotic cells. Tumor immunotherapy is an important means and clinical strategy for the treatment of some cancers. 5-Methylcytosine (m5C) is an important component of the epigenetic regulatory network discovered after m6A and has become a new topic for life science research in recent years. The m5C methylation of RNA can affect the fate of the modified RNA molecules and play an important role in various biological processes, including RNA stability, protein synthesis and transcriptional regulation. Recent studies have shown that m5C writers, erasers and readers are related to a variety of cellular biological processes and systemic diseases, including the occurrence, metastasis and tumor immune microenvironment. m5C methylation can widely affect gene expression and the biological process of tumorigenesis and development at multiple levels, but its specific mechanism and potential interaction with other epigenetic modifications in tumor immunotherapy are still unclear, and its regulatory mechanism, risk assessment and role in targeted therapy for malignant tumors need to be further studied. This article will review the dynamic regulatory network of m5C, the biological role of m5C modification in solid tumors and potential targets in tumor immunotherapy.
ABSTRACT
ObjectiveTo explore the effect and mechanism of Sishenwan-containing serum on aerobic glycolysis in human colon cancer HCT116 cells. MethodCell counting kit-8 （CCK-8） was used to detect the cell viability of colon cancer HCT116 cells after treatment with Sishenwan-containing serum （2.5%， 5%， and 10%） for 24， 48， 72 h. The concentration of lactic acid， the content of intracellular glucose， and the activity of hexokinase （HK） and fructose-6-phosphate kinase （PFK） in the cell culture medium were detected by the micro-method. The content of glucose transporter 1 （GluT1） mRNA was detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of GluT1 and methyltransferase-like 3 （MettL3） was detected by Western blot. The expression of GluT1 in cells was detected by immunofluorescence and the level of N6-methyladenosine （m6A） RNA methylation was detected by colorimetry. ResultCompared with the normal serum， 2.5%， 5%， and 10% Sishenwan-containing serum had no significant effect on the viability of HCT116 cells at 24 h， while 10% Sishenwan-containing serum showed a significant inhibitory effect on the viability of HCT116 cells at 48 h （P<0.05）. Hence， 10% Sishenwan-containing serum was used in subsequent experiments， and the intervention time was 48 h. Compared with the normal serum， 10% Sishenwan-containing serum could reduce lactate production （P<0.05）， down-regulate glucose uptake （P<0.05）， and blunt the activities of HK and PFK， the key rate-limiting enzymes of glycolysis （P<0.05）. Meanwhile， 10% Sishenwan-containing serum could decrease the expression of GluT1 protein （P<0.01） and mRNA （P<0.05） and reduce the proportion of cells expressing GluT1 （P<0.01）. Compared with the normal serum， Sishenwan-containing serum also decreased the protein content of MettL3 （P<0.05） and the methylation level of m6A RNA （P<0.01）. ConclusionSishenwan can inhibit glycolysis in colon cancer cells， and its inhibitory mechanism may be related to reducing MettL3 overexpression， inhibiting m6A RNA methylation， and down-regulating GluT1 and the activities of intracellular aerobic glycolysis-related enzymes such as HK and PFK.
ABSTRACT
RNA methylation is of great significance in the regulation of gene expression, among which the more important methylation modifiers are N6-methyladenosine (m6A) and 5-methylcytosine (m5C). The methylation process is mainly regulated by 3 kinds of proteins: methyltransferase, demethylase, and reader. m6A, m5C, and their related proteins have high abundance in the brain, and they have important roles in the development of the nervous system and the repair and remodeling of the vascular system. The neurovascular unit (NVU) is a unit of brain structure and function composed of neurons, capillaries, astrocytes, supporting cells, and extracellular matrix. The local microenvironment for NVU has an important role in nerve cell function repair, and the remodeling of NVU is of great significance in the prognosis of various neurological diseases.
Subject(s)
5-Methylcytosine , Adenosine/metabolism , Methylation , Methyltransferases/metabolism , RNAABSTRACT
The biological role of N 6-methyladenine (m 6A) methylation modification has been gradually identified, and it has shown increasing value in tumor. In recent years, with the accumulated explore of epigenetics in RNA modification, many studies have reported that m 6A methylation modification contributes to development and progression of lung cancer. m 6A-related modified regulator has potential application value as a clinical target for diagnosis and treatment of lung cancer.
ABSTRACT
N6-methyladenosine is one of the most prevalent mRNA modification in eukaryotes. The regulation of this pervasive mark is a dynamic and reversible process. m⁶A RNA methylation is catalyzed by m⁶A writers, removed by m⁶A erasers and recognized by m⁶A readers, thereby regulating multiple RNA processes including alternative splicing, nuclear export, degradation and translation. Accumulated evidence suggests that m⁶A modification plays a crucial role in the pathogenic mechanism and malignant progression in non-small cell lung cancer (NSCLC), including cell survival, proliferation, migration, invasion, tumor metastasis and drug resistance. Moreover, the expression of m⁶A and its related proteins are dysregulated in clinical samples and circulating tumor cells (CTCs) of lung cancer patients, indicating that m⁶A modification may serve as a novel potential biomarker for the diagnosis and prognosis of lung cancer. In this review, by summarizing a great number of recent reports related to m⁶A's function and its modulators, we aim to provide a new insight on the early diagnosis and drug development in NSCLC therapy. .
ABSTRACT
@#In recent decades, although great progress has been made on the diagnosis and treatment of oral squamous cell carcinoma (OSCC), its 5-year survival rate has not been significantly improved. The basic reason is the unclear pathogenesis, lack of effective molecular markers for assessing invasion, metastasis, and recurrence as well as therapeutic targets. The present view is that genetic and epigenetic abnormalities are related to the occurrence and development of OSCC. Epigenetic inheritance is a biological behavior that can be regulated and reversed, and it plays an important role in the occurrence and development of malignant tumors. First, this review will describe the role of epigenetic modifications in the development of OSCC in combination with our research and the latest research progress of epigenetics, including DNA methylation, RNA methylation, short noncoding RNAs (miRNAs, etc.), long noncoding RNAs, circular RNAs, histone modifications (acetylation and methylation), chromatin remodeling and genomic imprinting. Then, we will analyze the value of epigenetic studies in the prevention, diagnosis, and targeted therapy of OSCC.
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As the most prevalent and abundant transcriptional modification in the eukaryotic genome, the continuous and dynamic regulation of N6-methyladenosine (m6A) has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases (CVDs), such as ischemic heart failure (HF), myocardial hypertrophy, myocardial infarction (MI), and cardiomyogenesis. Regulation is achieved by modulating the expression of m6A enzymes and their downstream cardiac genes. In addition, this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs. However, the exact molecular mechanism of m6A epigenetic regulation has not been fully elucidated. In this review, we outline recent advances and discuss potential therapeutic strategies for managing m6A in relation to several common CVD-related metabolic disorders and external environmental factors. Note that an appropriate understanding of the biological function of m6A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms. Finally, it can provide new insights for the development of novel therapeutic agents for use in clinical practice.
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RNA N6-methyladenosine (m6A) modification is one of the most pervasive epigenetic modifications that correlate with gene expression, regulated by a variety of methylases, demethylases and reader proteins. m6A has been found crucial during cancer progression, aberrant changes of which contribute to tumorigenesis and metastasis. It's also been reported to be influential on chemotherapy and radiotherapy resistance of malignant tumors by inducing cancer stem cells (CSC) generation and enhancing post-therapy damage resistance, thus causing the progression or recurrence. In this review, we review the regulation of RNA m6A modification and focus on recent advances in functions of dysregulated m6A modification in the pathogenesis of cancer progression and recurrence. In addition, we also discuss the possible participation of CSC in this process combining current perspectives on the chemotherapy and radiotherapy resistance mechanism of CSC.
ABSTRACT
As the most prevalent and abundant transcriptional modification in the eukaryotic genome, the continuous and dynamic regulation of N6-methyladenosine (m6A) has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases (CVDs), such as ischemic heart failure (HF), myocardial hypertrophy, myocardial infarction (MI), and cardiomyogenesis. Regulation is achieved by modulating the expression of m6A enzymes and their downstream cardiac genes. In addition, this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs. However, the exact molecular mechanism of m6A epigenetic regulation has not been fully elucidated. In this review, we outline recent advances and discuss potential therapeutic strategies for managing m6A in relation to several common CVD-related metabolic disorders and external environmental factors. Note that an appropriate understanding of the biological function of m6A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms. Finally, it can provide new insights for the development of novel therapeutic agents for use in clinical practice.
ABSTRACT
Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N-methyladenosine (mA) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, mA can be incorporated by a methyltransferase complex and removed by demethylases, which ensures that the mA modification is reversible and dynamic. Moreover, mA is recognized by the YT521-B homology (YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the mA recognition by YTH domain-containing proteins, which would shed new light on mA-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.