The Cypripedium forrestii is an orchid species with extremely small populations (PSESP) in Yunnan, China. C. forrestii is range-restricted and less-studied than many orchid species, and it is exposed to various threats to its survival. We investigated its potential habitats and collected 52 samples from eight locations, as well as two outgroup species for reference. We developed genetic markers (SNPs) for C. forrestii based on transcriptome sequencing (RNA-seq) data, and analyzed the genetic diversity, population structure, gene flow and demographic history of C. forrestii in detail. C. forrestii is a taxonomically independent species to protect. We found that the genetic diversity of C. forrestii was very low (1.7e -4 ) compared with other endangered species. We identified three genetic clusters, and several populations with distinct genetic backgrounds. Most genetic diversity was found within sampling sites (87.87%) and genetic clusters (91.39%). Gene flow has been greatly limited over the most recent generations, probably due to geographical distance, historical climate change and habitat fragmentation. We also detected a severe bottleneck event brought about by the recent population constraints. These factors, together with its reproductive characteristics, contribute to the population fragmentation and low genetic diversity of C. forrestii . Based on our findings, we suggest an integrative conservation strategy to protect and recover the genetic diversity of C. forrestii and a further comprehensive study of its ecological traits in the future.
While microRNAs (miRNAs) are known to play a critical role in the progression of colorectal cancer, the role of miR-107 remains unknown. We evaluated its role and explored the underlying mechanism. MTT, wound-healing, transwell migration and transwell invasion assays were performed to evaluate the role of miR-107 in SW629 cell proliferation, migration and invasion. Real time-PCR and dual-luciferase reporter gene, TFR1 overexpression and western blotting assays were used to explore the underlying mechanism. MiR-107 is downregulated in colorectal cancer tissues and several human colorectal cancer cell lines. Low miR-107 expression often indicates a poor survival rate for colorectal cancer patients. MiR-107 suppresses the proliferation, migration and invasion of SW620 cells by negatively regulating transferrin receptor 1 (TFR1). MiR-107 suppresses the metastasis of colorectal cancer and could be a potential therapy target in colorectal cancer patients.
Circulating tumor DNA (ctDNA) has been recognized as a promising biomarker for colorectal cancer (CRC) early diagnosis and postoperative monitoring. However, we hypothesize that the clinical value of ctDNA sequencing may differ for colon cancer (CC) and rectal cancer (RC).Forty-three patients with primary CRC were prospectively enrolled. Tumor tissue samples, paired preoperative plasma samples and a series of postoperative plasma samples were obtained. Mutations in each sample were identified and compared.For 73.0% patients, at least one concordant mutation was detected in both tumor tissue DNA and paired preoperative ctDNA. The mutation concordance rate were higher in CC patients compared to RC patients (92.3% vs 45.5%; p= 0.004). For early stage patients, the mutation concordance rate was 72.7%. The recurrence rate was 33.3% for patients with postoperative ctDNA positive mutations, and 3.4% for patients with negative ctDNA (HR 10.767; 95% CI 1.1-103.8; p= 0.040).Liquid biopsy via ctDNA sequencing has great potential for the early detection and postoperative monitoring of CRC. The DNA of CC tissues is more likely to be released into blood than the DNA of RC tissues. This should be considered when diagnosing CRC patients with ctDNA sequencing technology.
Abstract Background According to the Global Cancer Statistics in 2020, the incidence and mortality of colorectal cancer (CRC) rank third and second among all tumors. The disturbance of ubiquitination plays an important role in the initiation and development of CRC, but the ubiquitinome of CRC cells and the survival-relevant ubiquitination are poorly understood. Methods The ubiquitinome of CRC patients (n = 6) was characterized using our own data sets of proteomic and ubiquitin-proteomic examinations. Then, the probable survival-relevant ubiquitination was searched based on the analyses of data sets from public databases. Results For the ubiquitinomic examination, we identified 1690 quantifiable sites and 870 quantifiable proteins. We found that the highly-ubiquitinated proteins (n ≥ 10) were specifically involved in the biological processes such as G-protein coupling, glycoprotein coupling, and antigen presentation. Also, we depicted five motif sequences frequently recognized by ubiquitin. Subsequently, we revealed that the ubiquitination content of 1172 proteins were up-regulated and 1700 proteins were down-regulated in CRC cells versus normal adjacent cells. We demonstrated that the differentially ubiquitinated proteins were relevant to the pathways including metabolism, immune regulation, and telomere maintenance. Then, integrated with the proteomic datasets from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) (n = 98), we revealed that the increased ubiquitination of FOCAD at Lys583 and Lys587 was potentially associated with patient survival. Finally, we depicted the mutation map of FOCAD and elucidated its potential functions on RNA localization and translation in CRC. Conclusions The findings of this study described the ubiquitinome of CRC cells and identified abnormal ubiquitination(s) potentially affecting the patient survival, thereby offering new probable opportunities for clinical treatment.
Additional file 1: Table S1. Clinical characteristics of the study population. Table S2. The primers of miRNAs validated by qRT-PCR. Table S3. Annotation of sRNAs sequences. Table S4. All Expressed known miRNA. Table S5. All novel or predicted candidate miRNAs (PC miRNAs) in this study. Table S6. Differentially expressed known miRNAs between the CT and CN libraries. Table S7. Differentially expressed novel miRNAs between the CT and CN libraries. Table S8. Differentially expressed miRNAs between the early-stage I-II (CT-E) and advanced-stage III-IV (CT-A) libraries. Table S9. All targets of known miRNAs. Table S10. All targets of novel miRNAs. Table S11. Potential target genes of DEmiRNAs.
Objective To study the common cause of the presacral venous massive hemorrhage and the methods of prevention and treatment during the operation of rectal cancer.Methods From January 1999 to June 2003,7 cases with presacral venous massive hemorrhage during the operation of rectal cancer were analyzed retrospectively.According to the site and status of bleeding,the drowing pin and iodoform guaze were used to control the bleeding.Results Hemotasis was obtained successfully in 6 cases and they were cured to discharge from hospital. One case died from hemostatic failure. Conclusion Main cause of presacral venous massive hemorrhage is due to unsuitable surgical manipulation.TME is the key point to prevent presacral venous massive bleeding.Dressing grawing pin and lodoform gauze tamponade are effective method for treating the presacral venous massive bleeding.
The aim of this study is to identify expression-based genes features with genetic sequence data in colorectal cancer (CR) patients. We collected genes expression profiling of CR from TCGA and GEO databases. Univariate and multivariate Cox regression analysis were used to evaluate the prognostic function of 7-genes siguatures based on risk score. We constructed the risk score model based on the expression data of 7-genes signatures in CRC train data set, and then validated in the test data set and TCGA database through bioinformatics analysis. We identified 7-genes, which were associated with the prognosis of 2 GEO cohorts in 307 CRC patients ( p < 0. 01). Patients in train data set could be divided into high-risk and low-risk groups with significantly different Overall survival (OS) and Kaplan-Meier (KM) based on 7-genes signatures. The signatures of the 7-genes were successfully validated in the independent TCGA test cohort and showed excellent performance in risk stratification associated with existing gene-related traits. Functional enrichment analyses revealed potential functional roles of these different expression genes in tumorigenesis. Our research demonstrated that the novel 7-genes signatures could be used as a potential independent biomarker for predicting the survival of CR patient.
Mitochondria play leading roles in initiation and progression of colorectal cancer (CRC). Proteogenomic analyses of mitochondria of CRC tumor cells would likely enhance our understanding of CRC pathogenesis and reveal new independent prognostic factors and treatment targets. However, comprehensive investigations focused on mitochondria of CRC patients are lacking. Here, we investigated global profiles of structural variants, DNA methylation, chromatin accessibility, transcriptome, proteome, and phosphoproteome on human CRC. Proteomic investigations uncovered greatly diminished mitochondrial proteome size in CRC relative to that found in adjacent healthy tissues. Integrated with analysis of RNA-Seq datasets obtained from the public database containing mRNA data of 538 CRC patients, the proteomic analysis indicated that proteins encoded by 45.5% of identified prognostic CRC genes were located within mitochondria, highlighting the association between altered mitochondrial function and CRC. Subsequently, we compared structural variants, DNA methylation, and chromatin accessibility of differentially expressed genes and found that chromatin accessibility was an important factor underlying mitochondrial gene expression. Furthermore, phosphoproteomic profiling demonstrated decreased phosphorylation of most mitochondria-related kinases within CRC versus adjacent healthy tissues, while also highlighting MKK3/p38 as an essential mitochondrial regulatory pathway. Meanwhile, systems-based analyses revealed identities of key kinases, transcriptional factors, and their interconnections. This research uncovered a close relationship between mitochondrial dysfunction and poor CRC prognosis, improve our understanding of molecular mechanism underlying mitochondrial linked to human CRC, and facilitate identifies of clinically relevant CRC prognostic factors and drug targets.
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