Adenosine-to-inosine (A-to-I), one of the most prevalent RNA modifications, has recently garnered significant attention. The A-to-I modification actively contributes to biological and pathological processes by affecting the structure and function of various RNA molecules, including double-stranded RNA, transfer RNA, microRNA, and viral RNA. Increasing evidence suggests that A-to-I plays a crucial role in the development of human disease, particularly in cancer, and aberrant A-to-I levels are closely associated with tumorigenesis and progression through regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of A-to-I modification in cancer are not comprehensively understood. Here, we review the latest advances regarding the A-to-I editing pathways implicated in cancer, describing their biological functions and their connections to the disease.
Humans ; Adenosine/genetics* ; Inosine/genetics* ; RNA Editing ; Neoplasms/pathology* ; Animals ; MicroRNAs/metabolism*

OBJECTIVETo study expression of regucalcin (RGN) and prohibitin (PHB) genes in cirrhotic rat liver and to investigate the related effects of compound glutathione inosine injection (CGII) intervention.

METHODSForty male Wistar rats were randomly divided into a control group (n=12) and a model group (n=28).The model was established by injecting sterile porcine serum (0.5 mL) into the rat abdominal cavity, twice weekly for 8 consecutive weeks; the control group rats were treated with physiological saline injection (0.5 mL) into the abdominal cavity with the same frequency and time span. During the modeling period, four rats from the model group were randomly selected at different time points to examine changes in liver pathology. Upon pathology confirmation of liver cirrhosis, the porcine serum injection was terminated. The remaining 24 rats in the model group were randomly divided into a fibrosis group and a CGII treatment group.The CGII group received CGII (intramuscular injection of 0.018 mL 100g-1 body weight) once a day for 6 continuous weeks; the fibrosis rats were treated with the same dosage of physiological saline with the same frequency and time span.Liver tissue morphology was examined by both hematoxylin-eosin and Masson's staining. RGN and PHB expression at the mRNA and protein levels in liver tissues were detected by real time RT-PCR and immunohistochemical staining, respectively.

RESULTSBoth the mRNA and protein expression levels of RGN and PHB were significantly lower in the liver tissues of the fibrosis group than in the control group.CGII intervention led to significant alleviation of the liver fibrosis severity; moreover, the mRNA and protein expression levels of RGN and PHB were significantly higher than those in the fibrosis group.

CONCLUSIONDown-regulation of regucalcin and prohibitin gene expression might contribute to the pathogenesis of liver cirrhosis.

Animals ; Calcium-Binding Proteins ; genetics ; Down-Regulation ; Gene Expression ; Glutathione ; toxicity ; Inosine ; Intracellular Signaling Peptides and Proteins ; genetics ; Liver Cirrhosis ; genetics ; Male ; Rats ; Rats, Wistar ; Repressor Proteins ; genetics

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo GMP biosynthesis. The expression and activity of IMPDH can be affected by diseases and physiological process. It is the drug target for anticancer, antiviral, antimicrobial and immunosuppressive therapeutics. Not only catalytic action but the other biological functions of IMPDH also play an important role in diseases. The basic functions, mechanism of catalysis, classification of inhibitors, biological functions and the latest advances to IMPDH will be illustrated in this review. It is expected to be helpful to the discovery of new inhibitors and biological functions of IMPDH.
Animals ; Binding Sites ; Catalysis ; Drug Design ; Drug Discovery ; Enzyme Inhibitors ; classification ; pharmacology ; Humans ; IMP Dehydrogenase ; antagonists & inhibitors ; genetics ; metabolism ; Inosine Monophosphate ; metabolism ; Molecular Structure ; NAD ; metabolism ; Polymorphism, Genetic

OBJECTIVEIt has been reported that neuronal apoptosis plays a critical role in pathology of hypoxic-ischemic encephalopathy (HIE). Cytochrome C (CytC) is an important apoptotic protease activating factor. Inosine might have a neuroprotective effect against cerebral ischemia reperfusion injury by inhibiting the neuronal apoptosis and the expression of CytC mRNA in adult rats. This study examined the effects of inosine on neuronal apoptosis and CytC mRNA expression following hypoxic-ischemic brain damage (HIBD) in order to investigate the neuroprotectivity of inosine against cerebral ischemia injury in neonatal rats and the possible mechanism.

METHODSA total of 140 healthy 7-day-old Sprague-Dawley rat pups were randomly assigned into Control (n=40), HIBD (n=50) and Inosine treatment groups (n=50). HIBD rat models were established by ligating the left common carotid artery, followed by 8% O2 hypoxia exposure for 2 hrs in the HIBD and Inosine treatment groups. The Control group was not subjected to hypoxia-ischemia (HI). The Inosine treatment and the HIBD groups were randomly divided into 5 sub-groups sacrificed at 6 and 12 hrs, and 1, 3 and 7 days post- HI (n=10 each). The Control group rats were sacrificed at the corresponding time points (n=8 each). Inosine was administered to the Inosine treatment group by intraperitoneal injection immediately after HIBD at the dosage of 100 mg/kg twice daily for 7 days. TUNEL staining and in situ hybridization method was used to detect neuronal apoptosis and CytC mRNA expression respectively.

RESULTSFew apoptotic cells and CytC mRNA positive cells were found in brain tissues of the Control group. In the HIBD group, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas increased 6 hrs after HI, peaking at 1 day after HI and then decreased gradually. Until the 7th day, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas in the HIBD group remained significantly higher than in the Control group. Inosine treatment decreased the apoptotic cells and the CytC mRNA expression in both areas from 6 hrs to 7 days after HI compared with the HIBD group. The linear correlation analysis demonstrated that the number of apoptotic cells was positively correlated to the CytC mRNA expression in neonatal rats with HIBD (r=0.88, P < 0.01) .

CONCLUSIONSInosine can reduce the number of apoptotic cells and down-regulate the expression of CytC mRNA following HIBD in neonatal rats. The decreased number of apoptotic cells was positively correlated to the decreased CytC mRNA expression after inosine treatment, suggesting that inosine offered neuroprotectivity against HIBD possibly through inhibiting the CytC mRNA expression and resulting in a decrease of cell apoptosis.

Animals ; Apoptosis ; drug effects ; Cytochromes c ; genetics ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; pathology ; In Situ Nick-End Labeling ; Inosine ; pharmacology ; therapeutic use ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley