Male infertility is a worldwide health issue,affecting 8%–12%of the global population.Oligoasthenoteratozoospermia(OAT)represents a severe type of male infertility,characterized by reduced sperm count and motility an...Male infertility is a worldwide health issue,affecting 8%–12%of the global population.Oligoasthenoteratozoospermia(OAT)represents a severe type of male infertility,characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology.Using whole-exome sequencing,this study identified a novel missense mutation(c.848C>A,p.A283E)in the coiled-coil domain-containing 34 gene(CCDC34)in a consanguineous Pakistani family.This rare mutation was predicted to be deleterious and to affect the protein stability.Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms.These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms,thus expanding the phenotypic spectrum of CCDC34 missense mutations.展开更多
目的探索乳腺癌组织及细胞系中CCDC34的表达情况及其对乳腺癌细胞增殖能力的影响。方法免疫组织化学染色方法检测34例乳腺癌组织及15例癌旁正常乳腺组织中CCDC34的表达和定位情况;利用Kaplan-Meier Plotter和The Human Protein Atlas数...目的探索乳腺癌组织及细胞系中CCDC34的表达情况及其对乳腺癌细胞增殖能力的影响。方法免疫组织化学染色方法检测34例乳腺癌组织及15例癌旁正常乳腺组织中CCDC34的表达和定位情况;利用Kaplan-Meier Plotter和The Human Protein Atlas数据库分析CCDC34与乳腺癌患者预后的相关性;Western blot检测人正常乳腺细胞MCF-10A及乳腺癌细胞SKBR-3、MCF-7、MDA-MB-453和MDA-MB-231中CCDC34的表达情况;在MCF-7和MDA-MB-231细胞中瞬时转染CCDC34,使用MTT的方法检测CCDC34对乳腺癌细胞增殖能力的影响。结果CCDC34在乳腺癌组织的表达显著低于癌旁正常乳腺组织(P<0.01);CCDC34在乳腺癌中的表达水平与患者的不良预后显著负相关(P<0.01);CCDC34在乳腺癌细胞中的表达普遍低于人正常乳腺细胞MCF-10A(P<0.01);MTT检测结果显示,转染CCDC34显著抑制了乳腺癌细胞MCF-7(Luminal A)和MDA-MB-231(basal)细胞的增殖能力(P<0.05)。结论乳腺癌组织及细胞系中CCDC34的表达普遍降低,CCDC34能够抑制乳腺癌细胞的增殖能力,并与乳腺癌患者的良好预后相关。展开更多
基金supported by the National Natural Science Foundation of China(No.82071709,No.32070850,and No.82171601)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Joint Fund for New Medicine of USTC(YD9100002034).
文摘Male infertility is a worldwide health issue,affecting 8%–12%of the global population.Oligoasthenoteratozoospermia(OAT)represents a severe type of male infertility,characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology.Using whole-exome sequencing,this study identified a novel missense mutation(c.848C>A,p.A283E)in the coiled-coil domain-containing 34 gene(CCDC34)in a consanguineous Pakistani family.This rare mutation was predicted to be deleterious and to affect the protein stability.Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms.These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms,thus expanding the phenotypic spectrum of CCDC34 missense mutations.
文摘目的探索乳腺癌组织及细胞系中CCDC34的表达情况及其对乳腺癌细胞增殖能力的影响。方法免疫组织化学染色方法检测34例乳腺癌组织及15例癌旁正常乳腺组织中CCDC34的表达和定位情况;利用Kaplan-Meier Plotter和The Human Protein Atlas数据库分析CCDC34与乳腺癌患者预后的相关性;Western blot检测人正常乳腺细胞MCF-10A及乳腺癌细胞SKBR-3、MCF-7、MDA-MB-453和MDA-MB-231中CCDC34的表达情况;在MCF-7和MDA-MB-231细胞中瞬时转染CCDC34,使用MTT的方法检测CCDC34对乳腺癌细胞增殖能力的影响。结果CCDC34在乳腺癌组织的表达显著低于癌旁正常乳腺组织(P<0.01);CCDC34在乳腺癌中的表达水平与患者的不良预后显著负相关(P<0.01);CCDC34在乳腺癌细胞中的表达普遍低于人正常乳腺细胞MCF-10A(P<0.01);MTT检测结果显示,转染CCDC34显著抑制了乳腺癌细胞MCF-7(Luminal A)和MDA-MB-231(basal)细胞的增殖能力(P<0.05)。结论乳腺癌组织及细胞系中CCDC34的表达普遍降低,CCDC34能够抑制乳腺癌细胞的增殖能力,并与乳腺癌患者的良好预后相关。
