Decorin(DCN)is primarily found in the connective tissues of various parts of the body,including the lungs,kidneys,bone tissue,aorta,and tendons.It is an important component of the extracellular matrix(ECM)and belongs ...Decorin(DCN)is primarily found in the connective tissues of various parts of the body,including the lungs,kidneys,bone tissue,aorta,and tendons.It is an important component of the extracellular matrix(ECM)and belongs to the class I small leucine-rich proteoglycans family.DCN is increasingly attracting attention due to its significant role in tumors,fibrotic diseases,and the regulation of vascular formation.Moreover,its anti-tumor properties have positioned it as a promising biomarker in the fight against cancer.Numerous studies have confirmed that DCN can exert inhibitory effects in various solid tumors,particularly in oral squamous cell carcinoma(OSCC),by activating its downstream pathways through binding with the epidermal growth factor receptor(EGFR)and mesenchymal-epithelial transition(MET)receptor,or by stabilizing and enhancing the expression of the tumor suppressor gene p53 to mediate apoptosis in cancer cells that have undergone mutation.The occurrence of OSCC is a continuous and dynamic process,encompassing the transition from normal mucosa to oral potentially malignant disorders(OPMDs),and further progressing from OPMDs to the malignant transformation into OSCC.We have found that DCN may exhibit a bidirectional effect in the progression of oral mucosal carcinogenesis,showing a trend of initial elevation followed by a decline,which decreases with the differentiation of OSCC.In OPMDs,DCN exhibits high expression and may be associated with malignant transformation,possibly linked to the increased expression of P53 in OPMDs.In OSCC,the expression of DCN is reduced,which can impact OSCC angiogenesis,and inhibit tumor cell proliferation,migration,and invasion capabilities,serving as a potential marker for predicting adverse prognosis in OSCC patients.This article reviews the current research status of DCN,covering its molecular structure,properties,and involvement in the onset and progression of oral mucosal carcinogenesis.It elucidates DCN’s role in this process and aims to offer insights for future investigations into its mechanism of action in oral mucosal carcinogenesis and its potential application in the early diagnosis and treatment of OSCC.展开更多
Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in ...Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in Gly→Ala at the N-terminal of PABPN1 protein that mimics the trinucleotide repeat expansion disease called Oculopharyngeal muscular dystrophy (OPMD). Molecular dynamics simulations in water with peptide models having sequence Ac-A10-GA2GG-NHme (peptide A) and Ac-A10A3GG-NHme (peptide B) reveal an increase in the length of helical segment in peptide B. The α-helical length is found to be stable in peptide B with starting geometry of a right handed helix, while in the case peptide A, the helical length is short. The interactions of water molecules at terminals, side chain-backbone interactions and hydrogen bonds provide stability to resultant conformation. The adopted helix by the poly-Ala stretch may lead to masking some other active parts of the PABPN1 that may trigger the aggregation, decrease in degradation and/or impaired function of protein. Hence, further studies with N-terminal may be helpful to understand unclear disease mechanism.展开更多
基金the National Key Laboratory of Oral Disease Prevention and Treatment of Open Subject Project(SKLOD2024OF04)Luzhou City Science and Technology Plan Project(2023RCX171)Sichuan Province Medical Research Project Program(S23043)。
文摘Decorin(DCN)is primarily found in the connective tissues of various parts of the body,including the lungs,kidneys,bone tissue,aorta,and tendons.It is an important component of the extracellular matrix(ECM)and belongs to the class I small leucine-rich proteoglycans family.DCN is increasingly attracting attention due to its significant role in tumors,fibrotic diseases,and the regulation of vascular formation.Moreover,its anti-tumor properties have positioned it as a promising biomarker in the fight against cancer.Numerous studies have confirmed that DCN can exert inhibitory effects in various solid tumors,particularly in oral squamous cell carcinoma(OSCC),by activating its downstream pathways through binding with the epidermal growth factor receptor(EGFR)and mesenchymal-epithelial transition(MET)receptor,or by stabilizing and enhancing the expression of the tumor suppressor gene p53 to mediate apoptosis in cancer cells that have undergone mutation.The occurrence of OSCC is a continuous and dynamic process,encompassing the transition from normal mucosa to oral potentially malignant disorders(OPMDs),and further progressing from OPMDs to the malignant transformation into OSCC.We have found that DCN may exhibit a bidirectional effect in the progression of oral mucosal carcinogenesis,showing a trend of initial elevation followed by a decline,which decreases with the differentiation of OSCC.In OPMDs,DCN exhibits high expression and may be associated with malignant transformation,possibly linked to the increased expression of P53 in OPMDs.In OSCC,the expression of DCN is reduced,which can impact OSCC angiogenesis,and inhibit tumor cell proliferation,migration,and invasion capabilities,serving as a potential marker for predicting adverse prognosis in OSCC patients.This article reviews the current research status of DCN,covering its molecular structure,properties,and involvement in the onset and progression of oral mucosal carcinogenesis.It elucidates DCN’s role in this process and aims to offer insights for future investigations into its mechanism of action in oral mucosal carcinogenesis and its potential application in the early diagnosis and treatment of OSCC.
文摘Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in Gly→Ala at the N-terminal of PABPN1 protein that mimics the trinucleotide repeat expansion disease called Oculopharyngeal muscular dystrophy (OPMD). Molecular dynamics simulations in water with peptide models having sequence Ac-A10-GA2GG-NHme (peptide A) and Ac-A10A3GG-NHme (peptide B) reveal an increase in the length of helical segment in peptide B. The α-helical length is found to be stable in peptide B with starting geometry of a right handed helix, while in the case peptide A, the helical length is short. The interactions of water molecules at terminals, side chain-backbone interactions and hydrogen bonds provide stability to resultant conformation. The adopted helix by the poly-Ala stretch may lead to masking some other active parts of the PABPN1 that may trigger the aggregation, decrease in degradation and/or impaired function of protein. Hence, further studies with N-terminal may be helpful to understand unclear disease mechanism.
