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Genetics and Molecular Biology, Volume: 45, Número: 3, Publicado: 2022
  • Circular RNA circENTPD7 suppresses the accumulation of PTEN to promote cell proliferation in non-small cell lung cancer Human And Medical Genetics

    Yu, Hongwei; Zhang, Yibin; Zhang, Lu; Yang, Rufei; Liao, Zhiwei; Zhou, Tongchong

    Resumo em Inglês:

    Abstract The oncogenic role of circular RNA ENTPD7 (circENTPD7) in cancer biology has been reported in glioblastoma, while its role in non-small cell lung cancer (NSCLC) is unknown. This study was performed to investigate the involvement of circENTPD7 in NSCLC. NSCLC tissues and paired non-tumor tissues were collected from 64 NSCLC patients and the expression of circENTPD7 and PTEN were determined by RT-qPCR. Expression levels of PTEN protein in these tissue samples were measured by ELISA. The 64 NSCLC patients were subjected to a follow-up study to explore the role of circENTPD7 in predicting the survival of NSCLC. Overexpression of circENTPD7 was achieved in NSCLC cells, and the effects of overexpression of circENTPD7 on the expression of PTEN were measured by RT-qPCR and Western blot at mRNA and protein level, respectively. Cell proliferation was assessed by CCK-8 assay. CircENTPD7 was upregulated in NSCLC and high expression levels of circENTPD7 predicts the poor survival rate of NSCLC cells. In NSCLC tissues, circENTPD7 was inversely correlated with PTEN protein but not mRNA. In NSCLC tissues, overexpression of circENTPD7 resulted in downregulation of PTEN, but did not alter the expression of PTEN mRNA. Cell proliferation analysis showed that overexpression of circENTPD7 promoted the proliferation of NSCLC cells and reduced the inhibitory effects of overexpression of PTEN on cell proliferation. CircENTPD7 may suppress the accumulation of PTEN to promote cell proliferation in NSCLC.
  • Alterations of actin cytoskeleton and arterial protein level in patients with obstructive jaundice Human And Medical Genetics

    Wang, Hong-Qian; Meng, Xiao-Yan; Zhang, Jin-Min; Chen, Jia-Ying; Zhang, Bao-Hua; Wu, Fei-Xiang

    Resumo em Inglês:

    Abstract Vascular hypo-responsiveness to vasopressors in patients with obstructive jaundice (OJ) is a common anesthetic event, which leads to perioperative complications and increased mortality. The cause of this clinical issue remains unclear. In this study, we estimated the actin cytoskeleton and arterial protein level in the artery of OJ patients by proteomic analysis. Ten patients with OJ due to bile duct diseases or pancreatic head carcinoma were enrolled, while another ten non-jaundice patients with chronic cholecystitis or liver hemangioma as the control group. Vascular reactivity to noradrenaline was measured before anesthesia on the day of surgery. Artery samples in adjacent tissues of removed tumor were collected and evaluated by 2-dimensional electrophoresis. Proteins with differential expression were detected by MALDI-TOF mass spectrometry with immunoblot confirmation. The results confirmed the phenomenon of vascular hypo-reactivity in OJ patients as suppressed aortic response to noradrenaline were existed in these patients. We also found that actin cytoskeleton and several actin-binding proteins were up- or down-regulated in the artery of OJ patients. These proteins changed in OJ patents might be the basic mechanism of vascular hypo-reactivity, further studies to uncover the role of these proteins in OJ is critical for clinical treatment of these patients.
  • Identification of super-enhancer-associated transcription factors regulating glucose metabolism in poorly differentiated thyroid carcinoma Human And Medical Genetics

    Liu, Kun; Du, Yongrui; Li, Hui; Lin, Xuexia

    Resumo em Inglês:

    Abstract This study aimed to uncover transcription factors that regulate super-enhancers involved in glucose metabolism reprogramming in poorly differentiated thyroid carcinoma (PDTC). TCA cycle and pyruvate metabolism were significantly enriched in PDTC. Differentially expressed genes in PDTC vs. normal control tissues were located in key steps in TCA cycle and pyruvate metabolism. A total of 23 upregulated genes localized in TCA cycle and pyruvate metabolism were identified as super-enhancer-controlled genes. Transcription factor analysis of these 23 super-enhancer-controlled genes related to glucose metabolism was performed, and 20 transcription factors were obtained, of which KLF12, ZNF281 and RELA had a significant prognostic impact. Regulatory network of KLF12, ZNF281 and RELA controlled the expression of these four prognostic target genes (LDHA, ACLY, ME2 and IDH2). In vitro validation showed that silencing of KLF12, ZNF281 and RELA suppressed proliferation, glucose uptake, lactate production and ATP level, but increased ADP/ATP ratio in PDTC cells. In conclusion, KLF12, ZNF281 and RELA were identified as the key transcription factors that regulate super-enhancer-controlled genes related to glucose metabolism in PDTC. Our findings contribute to a deeper understanding of the regulatory mechanisms associated with glucose metabolism in PDTC, and advance the theoretical development of PDTC-targeted therapies.
  • Clinical genomics and precision medicine Human And Medical Genetics

    Pena, Sérgio D. J.; Tarazona-Santos, Eduardo

    Resumo em Inglês:

    Abstract Precision Medicine emerges from the genomic paradigm of health and disease. For precise molecular diagnoses of genetic diseases, we must analyze the Whole Exome (WES) or the Whole Genome (WGS). By not needing exon capture, WGS is more powerful to detect single nucleotide variants and copy number variants. In healthy individuals, we can observe monogenic highly penetrant variants, which may be causally responsible for diseases, and also susceptibility variants, associated with common polygenic diseases. But there is the major problem of penetrance. Thus, there is the question of whether it is worthwhile to perform WGS in all healthy individuals as a step towards Precision Medicine. The genetic architecture of disease is consistent with the fact that they are all polygenic. Moreover, ancestry adds another layer of complexity. We are now capable of obtaining Polygenic Risk Scores for all complex diseases using only data from new generation sequencing. Yet, review of available evidence does not at present favor the idea that WGS analyses are sufficiently developed to allow reliable predictions of the risk components for monogenic and polygenic hereditary diseases in healthy individuals. Probably, it is still better for WGS to remain reserved for the diagnosis of pathogenic variants of Mendelian diseases.
  • Saint Peter and Saint Paul Archipelago barcoded: Fish diversity in the remoteness and DNA barcodes reference library for metabarcoding monitoring Animal Genetics

    Cruz, Marcelo Merten; Hoffmann, Lilian Sander; Freitas, Thales R. O. de

    Resumo em Inglês:

    Abstract In order to monitor the effects of anthropogenic pressures in ecosystems, molecular techniques can be used to characterize species composition. Among molecular markers capable of identifying species, the cytochrome c oxidase I (COI) is the most used. However, new possibilities of biodiversity profiling have become possible, in which molecular fragments of medium and short-length can now be analyzed in metabarcoding studies. Here, a survey of fishes from the Saint Peter and Saint Paul Archipelago was barcoded using the COI marker, which allowed the identification of 21 species. This paved the way to further investigate the fish biodiversity of the archipelago, transitioning from barcoding to metabarcoding analysis. As preparatory steps for future metabarcoding studies, the first extensive COI library of fishes listed for these islands was constructed and includes new data generated in this survey as well as previously available data, resulting in a final database with 9,183 sequences from 169 species and 63 families of fish. A new primer specifically designed for those fishes was tested in silico to amplify a region of 262 bp. The new approach should guarantee a reliable surveillance of the archipelago and can be used to generate policies that will enhance the archipelago’s protection.
  • Comparative transcriptome analysis of different tissues of Rheum tanguticum Maxim. ex Balf. (Polygonaceae) reveals putative genes involved in anthraquinone biosynthesis Plant Genetics

    Hu, Yanping; Zhang, Huixuan; Sun, Jing; Li, Wenjing; Li, Yi

    Resumo em Inglês:

    Abstract Rheum tanguticum is a perennial herb and an important medicinal plant, with anthraquinones as its main bioactive compounds. However, the specific pathway of anthraquinone biosynthesis in rhubarb is still unclear. The accumulation of anthraquinones in different tissues (root, leaf, stem and seed) of R. tanguticum revealed considerable variation, suggesting possible differences in metabolite biosynthetic pathways and accumulation among various tissues. To better illustrate the biosynthetic pathway of anthraquinones, we assembled transcriptome sequences from the root, leaf, stem and seed tissues yielding 157,564 transcripts and 88,142 unigenes. Putative functions could be assigned to 56,911 unigenes (64.57%) based on BLAST searches against annotation databases, including GO, KEGG, Swiss-Prot, NR, and Pfam. In addition, putative genes involved in the biosynthetic pathway of anthraquinone were identified. The expression profiles of nine unigenes involved in anthraquinone biosynthesis were verified in different tissues of R. tanguticum by qRT-PCR. Various transcription factors, including bHLH, MYB_related, and C2H2, were identified by searching unigenes against plantTFDB. This is the first transcriptome analysis of different tissues of R. tanguticum and can be utilized to describe the genes involved in the biosynthetic pathway of anthraquiones, understanding the molecular mechanism of active compounds in R. tanguticum.
  • Development and identification of an elite wheat-Hordeum californicum T6HcS/6BL translocation line ND646 containing several desirable traits Plant Genetics

    Wang, Zhangjun; Li, Qingfeng; Liu, Caixia; Liu, Fenglou; Xu, Nali; Yao, Mingming; Yu, Huixia; Wang, Yanqing; Chen, Jiajing; Bai, Shuangyu; Yang, Jingxin; Sun, Gang; Long, Jiaohui; Fan, Yalei; Kang, Ling; Li, Hongxia; Zhang, Xiaogang; Liu, Shengxiang

    Resumo em Inglês:

    Abstract Hordeum californicum (H. californicum, 2n=2X=14, HcHc), one of the wild relatives of wheat (Triticum aestivum L.), harbors many desirable genes and is a potential genetic resource for wheat improvement. In this study, an elite line ND646 was selected from a BC4F5 population, which was developed using 60Co-γ irradiated wheat-H. californicum disomic addition line WJ28-1 (DA6Hc) as the donor parent and Ningchun 4 as the recurrent parent. ND646 was identified as a novel wheat-H. californicum 6HcS/6BL translocation line using genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), and H. californicum-specific expressed sequence tag (EST) markers. Further evaluation revealed that ND646 had excellent performance in several traits, such as a higher sedimentation value (SV), higher water absorption rate (WAR), and higher hardness index (HI). More importantly, it had more kernels per spike (KPS), a higher grain yields (GY), and good resistance to powdery mildew, leaf rust, and 2,4-D butylate (2,4-D). Its excellent phenotypic performance laid the foundation for further investigation of its genetic architecture and makes ND646 a useful germplasm resource for wheat breeding.
  • Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids Genetics Of Microorganisms

    Silva, Verônica Santana da; Machado, Carlos Renato

    Resumo em Inglês:

    Abstract The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.
  • MiR-137-mediated negative relationship between LGR4 and RANKL modulated osteogenic differentiation of human adipose-derived mesenchymal stem cells Cellular, Molecular And Developmental Genetics

    Fan, Cong; Li, Yulong

    Resumo em Inglês:

    ABSTRACT MicroRNA-137 (miR-137) has recently emerged as an osteogenic regulator in several cell lines. This study aimed to identify the function of miR-137 on the crosstalk between leucine rich repeat containing G protein-coupled receptor 4 (LGR4) and receptor activator of nuclear factor-κB ligand (RANKL), thus unveiling the critical role of LGR4-RANKL interplay in the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASCs). By examining the osteogenic capacity and possible downstream genes expression with miR-137 overexpression/knockdown, we found that miR-137 downregulated LGR4 while upregulating RANKL. According to the results of dual-luciferase reporter assay, LGR4 was validated as a direct target of miR-137. Surprisingly, a negative relationship between LGR4 and RANKL was confirmed by the knockdown of these two genes. Furthermore, RANKL inhibitor could alleviate or reverse the inhibitory effects on osteogenesis generated by LGR4 knockdown. Collectively, this study indicated that miR-137-induced a negative crosstalk between LGR4 and RANKL that could contribute to the osteogenic regulation of hASCs and provide more systematic and in-depth understanding of epigenetic modulation by miR-137.
  • The multiple roles of lipid metabolism in yeast physiology during beer fermentation Genomics And Bioinformatics

    Bonatto, Diego

    Resumo em Inglês:

    Abstract The ability of brewing yeasts (Saccharomyces cerevisiae and Saccharomyces pastorianus) to cope with the toxic effects of ethanol during beer fermentation depends on the modulation of lipid and lipid droplets (LDs) biosynthesis, which affects membrane fluidity. However, it has been demonstrated that lipids and LDs can modulate different biological mechanisms associated to ethanol tolerance, including proteostasis and autophagy, leading to the hypothesis that lipid and LDs biosynthesis are integrative processes necessary for ethanol tolerance in yeast. Supporting this hypothesis, a transcriptome and systems biology analyses indicated the upregulation of autophagy, lipid biosynthesis, and proteostasis (ALP)-associated genes in lager yeast during beer fermentation, whose respective proteins interact in a shortest-pathway ALP network. These results indicated a cross-communication between various pathways linked to inter-organelle autophagy, lipid metabolism, and proteostasis (ALP) during lager beer fermentation, thus highlighting the importance of lipids for beer fermentation.
  • The chloroplast genome of Rosa rugosa × Rosa sertata (Rosaceae): genome structure and comparative analysis Genomics And Bioinformatics

    Niu, Yuan; Luo, Yanyan; Wang, Chunlei; Xu, Qiong; Liao, Weibiao

    Resumo em Inglês:

    Abstract Rosa rugosa × Rosa sertata, which belongs to the family Rosaceae, is one of the native oil-bearing roses in China. Most research has focused on its essential oil components and medicinal values. However, there have been few studies about its chloroplast genome. In this study, the whole chloroplast genome of R. rugosa × R. sertata was sequenced, analyzed, and compared to other genus Rosa species. The chloroplast genome of R. rugosa × R. sertata is a circular structure and 157,120 bp in length. The large single copy and small single copy is 86,173 bp and 18,743 bp in size, respectively, and the inverted repeats are 26,102 bp in size. The GC content of the whole genome is 37.96%, while those of regions of LSC, SSC, and IR are 35.20%, 31.18%, and 42.73%, respectively. There are 130 different genes annotated in this chloroplast genome, including 84 protein coding genes, 37 tRNA genes, 8 rRNA genes, and 1 pseudogene. Phylogenetic analysis of 19 species revealed that R. rugosa × R. sertata belong to the Sect. Cinnamomeae. Overall, this study, providing genomic resources of R. rugosa × R. sertata, will be beneficial for species identification and biological research.
  • Erratum: Long noncoding RNA POU6F2-AS1 regulates lung cancer aggressiveness through sponging miR-34c-5p to modulate KCNJ4 expression Erratum

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