RESUMO
BACKGROUND: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. METHODS: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. RESULTS: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. CONCLUSIONS: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.
Assuntos
Variação Genética , Papillomavirus Humano 16 , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Filogenia , Humanos , Feminino , China , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/genética , Proteínas Oncogênicas Virais/genética , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/genética , Adulto , Pessoa de Meia-Idade , Mutação de Sentido IncorretoRESUMO
BACKGROUND: Cervical cancer is a common gynecological malignancy. Gene microarray found that TCP11 gene was highly expressed in cervical cancer. However, the effect of TCP11 gene on the proliferation, apoptosis and migration of cervical cancer cells and its underlying molecular mechanisms are unclear. METHODS: GEPIA database, tissue microarray, western blot and qRT-PCR were used to analyze the expression of TCP11 gene in cervical cancer tissues and cells and its relationship with patients' survival rate. The cell cycle and apoptosis were detected by flow cytometry, and the expressions of cell cycle and apoptosis related molecules and EMT-related molecules were detected by Western blot and qRT-PCR. RESULTS: The results showed that TCP11 gene was highly expressed in cervical cancer tissues and cells compared with normal cervical tissues and cells, and its expression was positively correlated with patients' survival rate. The results of proliferation and migration assays showed that TCP11 overexpression inhibited the proliferation and migration of HeLa and SiHa cells. The results showed that TCP11 overexpression blocked the cell cycle of HeLa and SiHa cells, decreased the expression of CDK1 and Cyclin B1, and increased the apoptosis and the expression of caspase-3, cleaved-caspase-3 and cleaved-PARP. TCP11 overexpression increased the protein and mRNA expression of EMT-related molecules ZO-1 and E-cadherin. Conversely, TCP11 knockdown promoted the proliferation of HeLa and SiHa cells and the migration of HeLa cells. CONCLUSIONS: TCP11 overexpression significantly inhibited the occurrence and development of cervical cancer cells, it may be a potentially beneficial biomarker for cervical cancer.
Assuntos
Proteínas de Membrana , Neoplasias do Colo do Útero , Feminino , Humanos , Apoptose/genética , Caspase 3 , Divisão Celular , Expressão Gênica , Células HeLa , Neoplasias do Colo do Útero/genética , Proteínas de Membrana/genéticaRESUMO
BACKGROUND: Cervical cancer is currently estimated to be the fourth most common cancer among women worldwide and the leading cause of cancer-related deaths in some of the world's poorest countries. C/EBPß has tumor suppressor effects because it is necessary for oncogene-induced senescence. However, C/EBPß also has an oncogenic role. The specific role of C/EBPß in cervical cancer as a tumor suppressor or oncoprotein is unclear. OBJECTIVE: To explore the role of the C/EBPß protein in cervical tumorigenesis and progression. METHODS: Quantitative RT-PCR was used to analyze C/EBPß (15 cervical cancer tissue samples and 15 corresponding normal cervical tissue samples), miR-661, and MTA1 mRNA expression in clinical samples (10 cervical cancer tissue samples and 10 corresponding normal cervical tissue samples). Immunohistochemistry was used to analyze C/EBPß (381 clinical samples), Ki67 (80 clinical samples) and PCNA ( 60 clinical samples) protein expression. MALDI-TOF MassARRAY was used to analyze C/EBPß gene methylation (13 cervical cancer tissues and 13 corresponding normal cervical tissues). Cell proliferation was analyzed by CCK-8 in cervical cancer cell lines. Western blotting and immunohistochemistry were performed to detect C/EBPß protein expression levels, and mRNA expression was analyzed by quantitative RT-PCR analysis. Flow cytometry was performed to measure cell cycle distribution and cell apoptosis. Colony formation, Transwell, cell invasion, and wound healing assays were performed to detect cell migration and invasion. RESULTS: C/EBPß protein expression was significantly reduced in cervical cancer tissues compared with cervicitis tissues (P < 0.01). Ki67 protein and PCNA protein expression levels were significantly higher in cervical cancer tissues compared with cervicitis tissues. The rate of C/EBPß gene promoter methylation of CpG12, 13, 14 and CpG19 in cervical cancer tissues was significantly increased compared with normal cervical tissue (P < 0.05). In addition, C/EBPß was overexpressed in cervical cancer cells and this overexpression inhibited cell proliferation, migration, invasion, arrested cells in S phase, and promoted apoptosis. CONCLUSIONS: We have demonstrated that C/EBPß decreased in cervical cancer tissues and overexpression of the C/EBPß gene in cervical cancer cells could inhibit proliferation, invasion and migration.
Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Cervicite Uterina , Feminino , Humanos , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Antígeno Ki-67/metabolismo , MicroRNAs/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Repressoras/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transativadores/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Cervicite Uterina/genéticaRESUMO
BACKGROUND: The mitochondrial (mt) genomes of 15 species of sucking lice from seven families have been studied to date. These louse species have highly dynamic, fragmented mt genomes that differ in the number of minichromosomes, the gene content, and gene order in a minichromosome between families and even between species of the same genus. RESULTS: In the present study, we analyzed the publicly available data to understand mt genome fragmentation in seal lice (family Echinophthiriidae) and gorilla louse, Pthirus gorillae (family Pthiridae), in particular the role of minichromosome split and minichromosome merger in the evolution of fragmented mt genomes. We show that 1) at least three ancestral mt minichromosomes of sucking lice have split in the lineage leading to seal lice, 2) one minichromosome ancestral to primate lice has split in the lineage to the gorilla louse, and 3) two ancestral minichromosomes of seal lice have merged in the lineage to the northern fur seal louse. Minichromosome split occurred 15-16 times in total in the lineages leading to species in six families of sucking lice investigated. In contrast, minichromosome merger occurred only four times in the lineages leading to species in three families of sucking lice. Further, three ancestral mt minichromosomes of sucking lice have split multiple times independently in different lineages of sucking lice. Our analyses of mt karyotypes and gene sequences also indicate the possibility of a host switch of crabeater seal louse to Weddell seals. CONCLUSIONS: We conclude that: 1) minichromosome split contributes more than minichromosome merger in mt genome fragmentation of sucking lice, and 2) mt karyotype comparison helps understand the phylogenetic relationships between sucking louse species.
Assuntos
Anoplura , Genoma Mitocondrial , Animais , Anoplura/genética , Ordem dos Genes , Gorilla gorilla/genética , FilogeniaRESUMO
We describe and illustrate a new species of sucking louse, Hoplopleura tunneya new species, from the Australian pale field rat, Rattus tunneyi Thomas (Rodentia: Muridae). Currently, 22 species of the genus Hoplopleura Enderlein, 1904 (Phthiraptera: Anoplura: Hoplopleuridae) are known from Australian endemic rodents. Among the seven new endemic rodent species of the genus Rattus in Australia, R. tunneyi is one of five hosts to Hoplopleura lice. In addition, we give a list of all the species of Hoplopleura known from Australian endemic rodents. Including the introduced species Polyplax spinulosa, the total number of sucking louse species known from Australian endemic rodents is now 24.
Assuntos
Anoplura , Ftirápteros , Animais , Austrália/epidemiologia , Espécies Introduzidas , Muridae , Neópteros , Ratos , RoedoresRESUMO
BACKGROUND: To investigate the genotype distribution of human papillomavirus (HPV) in infected Uygur and Han women in Xinjiang, China; analyze the HPV16 E6 gene polymorphism site and relationship with the development of cervical cancer. METHODS: The HPV16 E6 sequence was analyzed using the European standard prototype to perform an evolutionary tree. HPV16 E6-T295/T350, G295/G350, and T295/G350 GV230 vectors were stably transfected into cervical cancer C33A cells to analyze the cell proliferation, migration and invasion, apoptosis by CCK8 and clonogenic assays, transwell and cell scratch assays, FACS experiments. RESULTS: The total HPV infection rate was 26.390% (760/2879), whereas the Uygur 22.87% (196/857) and the Han was 27.89% (564/2022) (P < 0.05). Among 110 mutations, 65 cases of E6 genes were mutated at nucleotide 350 (T350G) with the leucine changing to valine (L83V). Moreover, there were 7 cases of E6 gene mutated at nucleotide 295 (T295G) with aspartic changing to glutamic (D64E). When E6 vector(s) of mutations sites were transfected into C33A cells, they were found to promote cellular proliferation, migration, invasion, and inhibit apoptosis. T295/G350-E6 was significantly stronger than G295/G350 and T295/T350, G295/G350 was significantly stronger than T295/T350 (P < 0.05). The T295/G350 had the strongest effect on C33A cells and G295/G350 was significantly stronger than T295/T350 (P < 0.05). CONCLUSIONS: The positive HPV infection rates differed between the Uygur and Han in Xinjiang, China, and the genotype distribution of infection was different. After transfecting C33A cells with different eukaryotic expression vectors, the T295/G350 mutation site promoted the proliferation, migration, and invasion of C33A cells to a greater extent than G295/G350; however, G295/G350 had a stronger effect than T295/T350.
RESUMO
BACKGROUND: Xinjiang is one of the regions with a high incidence of cervical cancer, and the genetic variation of human papillomavirus may increase its ability to infect the human body and enhance virus-mediated immune escape ability. METHODS: Sanger sequencing of the HPV16 genome from 165 samples positive for HPV16 infection and phylogenetic analysis of the E1 and E2 genes revealed the gene polymorphism of HPV16 in Xinjiang. RESULTS: The results showed that there were 109 samples with variations in HPV16 E1, 48 sites with nucleotide variations (19 missense variations and 29 synonymous variations), and 91 samples with variations in HPV16 E2, 25 sites with nucleotide variations (20 missense variations and five synonymous variations). CONCLUSIONS: From the phylogenetic tree results, 149 samples were of the European variant and 16 samples were of the Asian variant. No African or North American/Asian variant types were found.
Assuntos
Proteínas de Ligação a DNA/genética , Variação Genética , Papillomavirus Humano 16/genética , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , China/epidemiologia , Feminino , Humanos , Incidência , Filogenia , Neoplasias do Colo do Útero/epidemiologiaRESUMO
BACKGROUND: The typical single-chromosome mitochondrial (mt) genome of animals has fragmented into multiple minichromosomes in the lineage Mitodivisia, which contains most of the parasitic lice of eutherian mammals. These parasitic lice differ from each other even among congeneric species in mt karyotype, i.e. the number of minichromosomes, and the gene content and gene order in each minichromosome, which is in stark contrast to the extremely conserved single-chromosome mt genomes across most animal lineages. How fragmented mt genomes evolved is still poorly understood. We use Polyplax sucking lice as a model to investigate how tRNA gene translocation shapes the dynamic mt karyotypes. RESULTS: We sequenced the full mt genome of the Asian grey shrew louse, Polyplax reclinata. We then inferred the ancestral mt karyotype for Polyplax lice and compared it with the mt karyotypes of the three Polyplax species sequenced to date. We found that tRNA genes were entirely responsible for mt karyotype variation among these three species of Polyplax lice. Furthermore, tRNA gene translocation observed in Polyplax lice was only between different types of minichromosomes and towards the boundaries with the control region. A similar pattern of tRNA gene translocation can also been seen in other sucking lice with fragmented mt genomes. CONCLUSIONS: We conclude that inter-minichromosomal tRNA gene translocation orientated towards the boundaries with the control region is a major contributing factor to the highly dynamic mitochondrial genome organization in the parasitic lice of mammals.
Assuntos
Anoplura , Genoma Mitocondrial , Animais , Anoplura/genética , Genoma Mitocondrial/genética , Cariótipo , Mamíferos , Filogenia , RNA de Transferência/genéticaRESUMO
We describe two new species of sucking lice in the genus Hoplopleura Enderlein, 1904 (Psocodea: Phthiraptera: Hoplopleuridae) from Australia: Hoplopleura gracilicaudatusa n. sp. from the eastern chestnut mouse Pseudomys gracilicaudatus (Gould) (Rodentia: Muridae), and Hoplopleura nanusa n. sp. from the western chestnut mouse Pseudomys nanus (Gould) (Rodentia: Muridae). Pseudomys Gray is the most speciose genus of rodents endemic to Australia with 24 species; however, only two Pseudomys species have been reported previously to be hosts of sucking lice. The description of the new species in the present study doubles the number of sucking louse species known to parasitize Pseudomys mice and increases the total number of sucking louse species known from endemic Australian rodents from 21 to 23. Pseudomys gracilicaudatus and P. nanus are closely related murines that diverged ~1 MYA with distinct and widely separated extant geographic distributions. The two new Hoplopleura species described in the present study share some morphological characters and likely co-evolved and co-speciated with their chestnut mouse hosts.
Assuntos
Distribuição Animal , Anoplura/classificação , Murinae/parasitologia , Animais , Anoplura/crescimento & desenvolvimento , Feminino , Interações Hospedeiro-Parasita , Masculino , Northern Territory , Ninfa/classificação , Ninfa/crescimento & desenvolvimento , QueenslandRESUMO
INTRODUCTION: The aim of this study was to determine whether ZNF582 gene methylation and tissue protein expression can be used as a tool with high sensitivity and specificity for cervical cancer screening. We analyzed the correlation between promoter methylation of ZNF582 gene and cervical cancer and high risk HPV16/18 infection. METHODS: Tissue samples of normal cervical or chronic cervicitis (n=51), CIN (cervical intraepithelial neoplasia) (n=35), and cervical carcinoma (n=68) were tested for HPV16/18 infection by polymerase chain reaction (PCR). We also detected the methylation status of the ZNF582 gene promoter in the same tissues by methylation-specific PCR (MSP), then analyzed the correlation between ZNF582 promoter methylation and HPV16/18 infection. Immunohistochemistry was used to analyze ZNF582 gene expression in 152 cervical tissues. We detected ZNF582 mRNA expression in cervical tissues (including cancer and non-cancer) by real-time fluorescence quantitative PCR (qPCR). RESULTS: Among 93 high-grade cervical lesions (CINII and above) and cervical cancer samples, 57 cases were positive for HPV16/18 infection and 36 cases were negative. ZNF582 gene methylation occurred in 9 out of 51 cases in normal cervical tissues (17.6%), 16 of 35 cases in CIN tissues (45.7%), and 50 of 68 cases in cervical cancer (73.5%). The differences in methylation rate of the three groups were statistically significant (P<0.05). The ZNF582 methylation rate in the positive HPV16/18 infection group was 73.7%, while the negative group was 63.9%. Compared with normal tissues, ZNF582 protein was highly expressed in cervical cancer tissues, but mRNA expression was low. CONCLUSION: While ZNF582 protein is highly expressed in cervical cancer tissues, it was not sufficient for use as a standard for cervical cancer staging. On the other hand, ZNF582 promoter methylation had high specificity and sensitivity in detecting CINII and highly diseased cervical lesions and could be used as a diagnostic marker for cervical cancer of women.
RESUMO
Based on a comprehensive study of museum specimens, eight new species of sucking lice of the genus Hoplopleura Enderlein, 1904 (Psocodea: Phthiraptera: Hoplopleuridae), are described from six genera of Australian Old Endemic rodents: Conilurus Ogilby, 1838 (Rodentia: Muridae), Leggadina Thomas, 1910 (Rodentia: Muridae), Leporillus Thomas, 1906 (Rodentia: Muridae), Mesembriomys Palmer, 1906 (Rodentia: Muridae), Pogonomys Milne-Edwards, 1877 (Rodentia: Muridae), and Xeromys Thomas, 1889 (Rodentia: Muridae). The description of these new species increases the number of sucking louse species from endemic Australian rodents from 13 to 21 and extends the records of sucking lice to all of the 14 genera of endemic rodents in Australia. Our results show that sucking lice are much more diverse among rodents in Australia than previously known. Furthermore, the Australian Hoplopleura species are host specific-each Hoplopleura species, including the eight new species described in the present study, parasitizes only a single host species, except Hoplopleura irritans Kuhn and Ludwig, 1967 (Psocodea: Phthiraptera: Hoplopleuridae) and Hoplopleura melomydis Weaver, 2017 (Psocodea: Phthiraptera: Hoplopleuridae), each of which is found on two host species. An updated dichotomous key for identifying Australian Hoplopleura species is included.
Assuntos
Anoplura/classificação , Interações Hospedeiro-Parasita , Murinae/parasitologia , Animais , Anoplura/anatomia & histologia , Austrália/epidemiologia , Feminino , Infestações por Piolhos/epidemiologia , Infestações por Piolhos/parasitologia , Masculino , Prevalência , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/parasitologiaRESUMO
The evolution and phylogenetic relationships of the ticks at both the family and genus levels are contested. The genus Amblyomma and its subgenera are in a state of flux; moreover, the relationships among the three tick families are controversial due to conflicting phylogenetic support for different arrangements of the three families of living ticks. With 18 newly sequenced mitochondrial (mt) genomes of ticks included, we executed the largest mt genome phylogenetic study of ticks so far. Phylogenetic trees were inferred from one sea spider mt genome, one horseshoe crab, five mite mt genomes and 146 tick mt genomes from 120 species: 153 mt genomes in total. Sixteen phylogenetic trees were inferred from 10 datasets using both maximum likelihood and Bayesian inference methods. We describe the first novel mt gene-arrangement for the metastriate Ixodidae in Amblyomma (Africaniella) transversale. Also, three unusual partial 16S rRNA gene inserts were found in the mt genome of Haemaphysalis (Alloceraea) kitaokai: we consider the possible role of past genome translocation events in the formation of these inserts. Our phylogenies revealed evidence that: (i) the genus Amblyomma is polyphyletic with respect to Amblyomma (Africaniella) transversale; (ii) the subgenus Aponomma is apparently embedded in the genus Amblyomma; (iii) Haemaphysalis (Segalia) parva and Haemaphysalis (Alloceraea) kitaokai form a clade to the exclusion of other Haemaphysalis species; and (iv) the phylogenetic position of the family Nuttalliellidae is unstable among phylogenies from different datasets.
Assuntos
Amblyomma/genética , Argasidae/classificação , Evolução Biológica , Genoma Mitocondrial , Ixodidae/classificação , Filogenia , AnimaisRESUMO
We report for the first time the fragmented mitochondrial (mt) genomes of two Pedicinus species: Pedicinus obtusus and Pedicinus badii, and compared them with the lice of humans and chimpanzees. Despite being congeneric, the two monkey lice are distinct from each other in mt karyotype. The variation in mt karyotype between the two Pedicinus lice is the most pronounced among the congeneric species of sucking lice observed to date and is attributable to the opposite directions between them in mt karyotype evolution. Two of the inferred ancestral mt minichromosomes of the higher primate lice merged as one in the macaque louse whereas one of the ancestral minichromosomes split into two in the colobus louse after these two species diverged from their most recent common ancestor. Our results showed that mt genome fragmentation was a two-way process in the higher primate lice, and minichromosome merger was more common than previously thought.
Assuntos
Anoplura/genética , Evolução Molecular , Genoma Mitocondrial , Animais , Anoplura/classificação , Cromossomos de Insetos , Colobus , Feminino , Cariótipo , Macaca mulatta , Masculino , Filogenia , RNA de Transferência de Leucina/químicaRESUMO
BACKGROUND: Historical European exploration and colonization resulted in the introduction of four species of rodents to the Australian continent from Eurasia: the brown rat, Rattus norvegicus, the black rat, R. rattus, the Pacific rat, R. exulans, and the house mouse, Mus musculus. The spread of these rodents created opportunities for their co-introduced sucking lice to parasitize and adapt to endemic rodents in Australia. METHODS: We collected sucking lice from rodent specimens in seven museums across Australia. We identified the spiny rat louse, Polyplax spinulosa, based on morphology. We sequenced the mitochondrial cox1 and rrnL genes of P. spinulosa specimens and constructed a phylogenetic tree with rrnL sequences. RESULTS: We examined 989 rodent specimens of 54 species and collected 2111 adult sucking lice and 1064 nymphal sucking lice. We found that P. spinulosa had nearly doubled its host range by parasitizing at least six endemic rodent species in Australia. The other two introduced lice, P. serrata and Hoplopleura pacifica, however, have apparently failed to expand to any endemic rodents in Australia. Our analysis of mitochondrial rrnL gene sequences divided P. spinulosa into two genotypes (European vs Southeast Asian), which differ by 7.5%; both genotypes were introduced into Australia and then expanded their host ranges to include endemic rodents. CONCLUSIONS: The earliest record of a European ship landing in Australia was in 1606, followed by British settlement in 1788. The expansion of P. spinulosa to at least six endemic rodent species in Australia has therefore occurred in the time frame of 200 to 400 years, which is extremely rapid relative to its host expansion to eight native rat species in Eurasia in ~ 16 million years since it diverged from P. serrata. The host expansion of P. spinulosa is remarkable for a blood-sucking louse and is in stark contrast to the absence of host expansion by P. serrata and H. pacifica. Comparison among these three introduced sucking lice indicated that both louse-specific factors and host-specific factors can contribute to the success or failure of host expansion.
Assuntos
Anoplura/genética , Especificidade de Hospedeiro , Ratos/parasitologia , Doenças dos Roedores/parasitologia , Animais , Anoplura/fisiologia , Austrália , Feminino , Geografia , Masculino , Museus , Doenças dos Roedores/epidemiologiaRESUMO
BACKGROUND: Xinjiang is one of the areas with the highest incidence of cervical cancer in China. Genetic variation in Human papillomavirus type 16 (HPV16) may increase the ability of the virus to mediate carcinogenesis and immune escape, which are risk factors for the progression of cervical cancer. We investigated polymorphism in HPV16 and the distribution of its sub-lineages in the region by analyzing the E6, E7 and long control region (LCR) gene sequences from women with HPV16-positive cervical samples in Xinjiang. METHODS: A total of 138 cases of cervical lesions and squamous cell carcinoma with infection of HPV16 virus were collected. The E6 and E7 genes and LCR of HPV16 virus were sequenced and compared with the HPV16 European prototype reference and other HPV16 mutants for single nucleotide polymorphisms. Neighbor-joining phylogenetic trees were constructed using E6, E7 and LCR sequences. RESULTS: Fourteen missense mutations were found in the E6 gene; the loci with the highest mutation frequency were T350G (36/75, 48%) and T178G (19/75, 25.3%). In the E7 gene, the locus with the highest mutation frequency was A647G (18/75, 24%). A total of 33 polymorphic sites were found in the LCR, of which T7447C (39/95, 40.1%) was the most frequent. CONCLUSION: HPV16 in Xinjiang is mainly of the European variant, followed by the Asian variant type; no Africa 1, 2 or Asia-America variant types were found.
RESUMO
BACKGROUND & AIMS: Colorectal cancer is an epigenetically heterogeneous disease, however, the extent and spectrum of the CpG island methylator phenotype (CIMP) is not clear. METHODS: Genome-scale methylation and transcript expression were measured by DNA Methylation and RNA expression microarray in 216 unselected colorectal cancers, and findings were validated using The Cancer Genome Atlas 450K and RNA sequencing data. Mutations in epigenetic regulators were assessed using CIMP-subtyped Cancer Genome Atlas exomes. RESULTS: CIMP-high cancers dichotomized into CIMP-H1 and CIMP-H2 based on methylation profile. KRAS mutation was associated significantly with CIMP-H2 cancers, but not CIMP-H1 cancers. Congruent with increasing methylation, there was a stepwise increase in patient age from 62 years in the CIMP-negative subgroup to 75 years in the CIMP-H1 subgroup (P < .0001). CIMP-H1 predominantly comprised consensus molecular subtype 1 cancers (70%) whereas consensus molecular subtype 3 was over-represented in the CIMP-H2 subgroup (55%). Polycomb Repressive Complex-2 (PRC2)-marked loci were subjected to significant gene body methylation in CIMP cancers (P < 1.6 × 10-78). We identified oncogenes susceptible to gene body methylation and Wnt pathway antagonists resistant to gene body methylation. CIMP cluster-specific mutations were observed in chromatin remodeling genes, such as in the SWItch/Sucrose Non-Fermentable and Chromodomain Helicase DNA-Binding gene families. CONCLUSIONS: There are 5 clinically and molecularly distinct subgroups of colorectal cancer. We show a striking association between CIMP and age, sex, and tumor location, and identify a role for gene body methylation in the progression of serrated neoplasia. These data support our recent findings that CIMP is uncommon in young patients and that BRAF mutant polyps in young patients may have limited potential for malignant progression.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Ilhas de CpG , Metilação de DNA , Epigenoma , Mutação , Adenocarcinoma/classificação , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Fatores Etários , Idoso , Neoplasias Colorretais/classificação , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Epigenômica , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Oncogenes/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Sequência de RNARESUMO
We investigated the infection status and genotype distribution of human papillomavirus (HPV) in women of different ages and various ethnic groups in the Yili region, Xinjiang, China. We checked the HPV genotypes of 3,445 samples of exfoliated cervical cells using the PCR-reverse dot blot method. The total infection rate of HPV was 25.60% (882/3,445). The ethnic stratification showed that the infection rates were 22.87% (196/857) in Uygur, 21.55% (122/566) in Kazak, and 27.89% (564/2,022) in Han individuals. The most prevalent high-risk genotypes were HPV16, HPV52, and HPV53 in Uygur and Kazak and HPV16, HPV52, and HPV58 in Han ethnic groups. The age stratification showed that the infection rates in Han, Uygur, and Kazak women were up to 40.9% (61/149) in those aged 26-30 years, 41.5% (22/53) in those over 61 years old, and 30.2% (29/96) in those 46-50 years old, respectively. Therefore, HPV infection and HPV genotype distribution varied among the different age groups of the three ethnic groups.
Assuntos
Colo do Útero/virologia , Etnicidade , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , China/epidemiologia , China/etnologia , Técnicas Citológicas , Feminino , Genótipo , Humanos , Programas de Rastreamento , Papillomaviridae/genética , Vigilância em Saúde Pública , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/etiologiaRESUMO
Organelle genome fragmentation has been found in a wide range of eukaryotic lineages; however, its use in phylogenetic reconstruction has not been demonstrated. We explored the use of mitochondrial (mt) genome fragmentation in resolving the controversial suborder-level phylogeny of parasitic lice (order Phthiraptera). There are approximately 5000 species of parasitic lice in four suborders (Amblycera, Ischnocera, Rhynchophthirina, and Anoplura), which infest mammals and birds. The phylogenetic relationships among these suborders are unresolved despite decades of studies. We sequenced the mt genomes of eight species of parasitic lice and compared them with 17 other species of parasitic lice sequenced previously. We found that the typical single-chromosome mt genome is retained in the lice of birds but fragmented into many minichromosomes in the lice of eutherian mammals. The shared derived feature of mt genome fragmentation unites the eutherian mammal lice of Ischnocera (family Trichodectidae) with Anoplura and Rhynchophthirina to the exclusion of the bird lice of Ischnocera (family Philopteridae). The novel clade, namely Mitodivisia, is also supported by phylogenetic analysis of mt genome and cox1 gene sequences. Our results demonstrate, for the first time, that organelle genome fragmentation is informative for resolving controversial high-level phylogenies.
Assuntos
Anoplura/classificação , Anoplura/genética , Eutérios/parasitologia , Genoma Mitocondrial/genética , Filogenia , Animais , Fragmentação do DNARESUMO
BACKGROUND: The sucking louse fauna of endemic Australian rodents has been under-studied for decades. Sixty-five species of native rodents have been recorded in Australia. However, only 11 species of lice have been reported from 11 species of endemic Australian rodents. RESULTS: We describe a new species of sucking louse, Hoplopleura villosissima Wang (Psocodea: Phthiraptera: Hoplopleuridae), and report a new host record of the spiny rat louse, Polyplax spinulosa Burmeister, 1839 (Psocodea: Phthiraptera: Polyplacidae), from the long-haired rat, Rattus villosissimus Waite (Rodentia: Muridae), which is endemic to Australia. CONCLUSIONS: This study is the first record of sucking louse from R. villosissimus and the first record of a species of Polyplax Enderlein, 1904 from an endemic Australian rodent. This study brings the total number of sucking louse species in endemic Australian rodents from 11 to 13. Previously, only the introduced brown rat, Rattus norvegicus Berkenhout and the black rat, Rattus rattus Linnaeus were recorded as the hosts of P. spinulosa in Australia. Because R. villosissimus overlaps with R. rattus in distribution but not with R. norvegicus, we propose that P. spinulosa transferred to R. villosissimus from R. rattus.
Assuntos
Infestações por Piolhos/epidemiologia , Muridae/parasitologia , Ftirápteros/classificação , Ftirápteros/genética , Doenças dos Roedores/parasitologia , Animais , Austrália/epidemiologia , Infestações por Piolhos/parasitologiaRESUMO
This study aimed to explore: 1) DNA methylation in the promoter regions of Wilms tumor gene 1 (WT1), NK6 transcription factor related locus 1 gene (NKX6-1) and Deleted in bladder cancer 1 (DBC1) gene in cervical cancer tissues of Uygur women in Xinjiang, and 2) the correlation of gene methylation with the infection of HPV16/18 viruses. We detected HPV16/18 infection in 43 normal cervical tissues, 30 cervical intraepithelial neoplasia lesions (CIN) and 48 cervical cancer tissues with polymerase chain reaction (PCR) method. Methylation in the promoter regions of the WT1, NKX6-1 and DBC1 genes in the above-mentioned tissues was measured by methylation-specific PCR (MSP) and cloning sequencing. The expression level of these three genes was measured by real-time PCR (qPCR) in 10 methylation-positive cervical cancer tissues and 10 methylation-negative normal cervical tissues. We found that the infection of HPV16 in normal cervical tissues, CIN and cervical cancer tissues was 14.0, 36.7 and 66.7%, respectively. The infection of HPV18 was 0, 6.7 and 10.4%, respectively. The methylation rates of WT1, NKX6-1 and DBC1 genes were 7.0, 11.6 and 23.3% in normal cervical tissues, 36.7, 46.7 and 30.0% in CIN tissues, and 89.6, 77.1 and 85.4% in cervical cancer tissues. Furthermore, WT1, NKX6-1 and DBC1 genes were hypermethylated in the high-grade squamous intraepithelial lesion (CIN2, CIN3) and in the cervical cancer tissues with infection of HPV16/18 (both P< 0.05). The expression of WT1, NKX6-1 and DBC1 was significantly lower in the methylation-positive cervical cancer tissues than in methylation-negative normal cervical tissues. Our findings indicated that methylation in the promoter regions of WT1, NKX6-1 and DBC1 is correlated with cervical cancer tumorigenesis in Uygur women. The infection of HPV16/18 might be correlated with methylation in these genes. Gene inactivation caused by methylation might be related to the incidence and development of cervical cancer.