Soybean is one of the most important oil crops in the world. The domestication of wild soybean has resulted in significant changes in the seed oil content and seed size of cultivated soybeans. To ...better understand the molecular mechanisms of seed formation and oil content accumulation, WDD01514 (E1), ZYD00463 (E2), and two extreme progenies (E23 and E171) derived from RILs were used for weighted gene coexpression network analysis (WGCNA) combined with transcriptome analysis.
In this study, both seed weight and oil content in E1 and E171 were significantly higher than those in E2 and E23, and 20 DAF and 30 DAF may be key stages of soybean seed oil content accumulation and weight increase. Pathways such as "Photosynthesis", "Carbon metabolism", and "Fatty acid metabolism", were involved in oil content accumulation and grain formation between wild and cultivated soybeans at 20 and 30 DAF according to RNA-seq analysis. A total of 121 oil content accumulation and 189 seed formation candidate genes were screened from differentially expressed genes. WGCNA identified six modules related to seed oil content and seed weight, and 76 candidate genes were screened from modules and network. Among them, 16 genes were used for qRT-PCR and tissue specific expression pattern analysis, and their expression-levels in 33-wild and 23-cultivated soybean varieties were subjected to correlation analysis; some key genes were verified as likely to be involved in oil content accumulation and grain formation.
Overall, these results contribute to an understanding of seed lipid metabolism and seed size during seed development, and identify potential functional genes for improving soybean yield and seed oil quantity.
Transfer RNA-derived fragments (tRFs) are a class of small non-coding regulatory RNAs that are involved in the pathophysiology of many diseases. However, the role of tRFs in cancer progression ...remains largely elusive. Here, we demonstrate that a pan-cancer 3′-tRF, CAT1 (cancer associated tRF 1), is ubiquitously upregulated in tumors and associated with poor prognosis of a variety of cancers, including lung cancer. The upregulated CAT1 in cancer cells binds to RNA-binding protein with multiple splicing (RBPMS) and displaces NOTCH2 association from RBPMS, thereby inhibiting the subsequent CCR4-NOT deadenylation-complex-mediated NOTCH2 mRNA decay. The CAT1-enhanced NOTCH2 expression promotes lung cancer cell proliferation and metastasis in vitro and in vivo. In addition, plasma CAT1 levels are substantially increased in patients with lung cancer compared to non-cancer control subjects. Our findings reveal an intrinsic connection between cancer-specific upregulation of CAT1 and cancer progression, show the regulation of NOTCH signaling in cancer by a 3′-tRF, and highlight its great clinical potential.
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•CAT1 is upregulated and associated with poor prognosis in many types of cancer•Upregulated CAT1 in lung cancer cells displaces NOTCH2 bound to RBPMS•Displacement of CAT1 inhibits RBPMS/CCR4-NOT-mediated decay of NOTCH2 mRNA•CAT1 promotes lung carcinogenesis through regulation of NOTCH signaling
Yu et al. show that a pan-cancer 3′-tRF, CAT1, is upregulated in many human cancers and associated with poor prognosis and discovered that CAT1 interacts with RBPMS to regulate NOTCH signaling in cancer cells. These findings suggest that targeting CAT1 could be a promising strategy for non-invasive cancer diagnosis and therapy.
To assess the feasibility of validating microRNA (miRNA) profile related to paclitaxel-sensitivity in formalin-fixed paraffin-embedded (FFPE) samples of serous ovarian carcinoma (OC) patients.
...Deregulated miRNAs identified by miRNA microarray were further detected in 45 FFPE OC samples using Realtime PCR. Correlations between paired FFPE and frozen tumor samples were analyzed. Survival times were compared between 6 high and low miRNAs groups. Western blot and luciferase reporter assay were used for validating the target of miRNA.
Sixteen up-regulated miRNAs and twenty-three down-regulated miRNAs were revealed in pacilitaxel-resistant ST30 cells. The up-regulated miRNAs (miR-320a, 22 and 129-5p) and down-regulated miRNAs (miR-9, 155 and 640) were confirmed in paclitaxel-resistant FFPE tumor samples, compared with paclitaxel-sensitive samples. Higher miR-9 and miR-640 showed better survival time in OC patients. Expressions of miR-9, 155 and 22 in FFPE samples were closely mimicked by those in frozen tissues. RAB34 was validated as a direct target of miR-9.
We validated miRNA profile in pacilitaxel-resistant OC using FFPE samples, which might enable treatment stratification and help us to predict outcomes in OC patients. FFPE samples are feasible materials for miRNA research.
To investigate the detailed roles and mechanisms of tumor-derived exosomes in progression and metastasis of ovarian cancer in vitro.
Exosomes were isolated by differential centrifugation method; the ...morphology, size and biological markers of exosomes were separately defined by transmission electron microscopy, nanoS90 and Western blotting; Trans-well chambers assay was used to assess the ability of migration and invasion of recipient cells uptaking the exosomes from HO8910PM cells. The downstream molecule was screened by mass spectrometry.CD44 was identified by western blotting and the function of CD44 was identified by trans-well chambers assay and CCK8 assay.
Exosomes derived from HO8910PM cells could be transferred to HO8910 cells and promote cell migration and invasion in the recipient cells of ovarian cancer. And CD44 could be transferred to the HO8910 cells through exosomes from HO8910PM cells and influence the migration and invasion ability of HO8910 cells.
The more aggressive subpopulation can transfer a metastatic phenotype to the less one via secreting exosomes within a heterogeneous tumor. CD44 may be a potential therapeutic approach for ovarian cancer.
There are three main therapeutic strategies, namely expectant management (dilation and curettage only), prophylactic chemotherapy and prophylactic total hysterectomy for treating older women with ...complete hydatidiform mole (CHM). However, the scientific community has so far, not unanimously accepted the above-mentioned methods. The objective of this study was to evaluate the effectiveness of these therapeutic strategies in preventing post-molar gestational trophoblastic neoplasia (GTN) pertaining to patients with CHM who were at least 40 years old.
Hundred and seventy-one patients from our hospital who had histologically been diagnosed of CHM and underwent treatment from January 2004 to December 2013 were included. All patients were followed continuously for a minimum of 2 years after which relevant clinical data were extracted and analysed.
All patients were divided to three groups. Group 1 consisted of 124 patients, treated by expectant management, and the incidence of post-molar GTN was 37.1%. Group 2 included 12 patients who received prophylactic chemotherapy, with an incidence of 41.7%. The remaining 35 patients, Group 3, underwent prophylactic total hysterectomy, with the lowest incidence of 11.4%. A significantly lower incidence was noted in group 3 as compared to group 1 (P = 0.004). GTN patients who received prophylactic chemotherapy required, on average, longer time to be diagnosed of GTN and had higher probability of chemotherapy resistance (P = 0.031 and P = 0.024).
This retrospective analysis showed that prophylactic total hysterectomy was the most effective therapeutic strategy for treating CHM in women at least 40 years old of age.
Circular RNAs (circRNAs) are critical regulators in the occurrence and development of numerous cancers, in which abnormal autophagy plays a key role. However, the potential involvement of circRNAs in ...autophagy is largely unknown. Here, we identified the overexpression of circTICRR, a circular RNA, in cervical cancer. In vitro experiments showed that knockdown of circTICRR activated autophagy, and consequently promoted apoptosis and inhibited proliferation in cervical cancer cells, and vice versa. CircTICRR interacted with HuR protein via binding to F287/F289 in the RRM3 domain of HuR, stabilizing GLUD1 mRNA and elevating the level of GLUD1 protein. In vivo experiments revealed that knockdown of circTICRR suppressed the growth of transplanted tumors. An inhibitory peptide specific to the binding site between circTICRR and HuR protein promoted autophagy, induced apoptosis, suppressed proliferation in cervical cancer cells, and inhibited the growth of xenografts. Our findings suggest that circTICRR acts as an oncogene in cervical cancer and the interaction between circTICRR and HuR protein may be a potential target in cervical cancer therapeutics.
Soybean brown rust (SBR), caused by
, is a devastating fungal disease that threatens global soybean production. This study conducted a genome-wide association study (GWAS) with seven models on a ...panel of 3,082 soybean accessions to identify the markers associated with SBR resistance by 30,314 high quality single nucleotide polymorphism (SNPs). Then five genomic selection (GS) models, including Ridge regression best linear unbiased predictor (rrBLUP), Genomic best linear unbiased predictor (gBLUP), Bayesian least absolute shrinkage and selection operator (Bayesian LASSO), Random Forest (RF), and Support vector machines (SVM), were used to predict breeding values of SBR resistance using whole genome SNP sets and GWAS-based marker sets. Four SNPs, namely Gm18_57,223,391 (LOD = 2.69), Gm16_29,491,946 (LOD = 3.86), Gm06_45,035,185 (LOD = 4.74), and Gm18_51,994,200 (LOD = 3.60), were located near the reported P. pachyrhizi R genes, Rpp1, Rpp2, Rpp3, and Rpp4, respectively. Other significant SNPs, including Gm02_7,235,181 (LOD = 7.91), Gm02_7234594 (LOD = 7.61), Gm03_38,913,029 (LOD = 6.85), Gm04_46,003,059 (LOD = 6.03), Gm09_1,951,644 (LOD = 10.07), Gm10_39,142,024 (LOD = 7.12), Gm12_28,136,735 (LOD = 7.03), Gm13_16,350,701(LOD = 5.63), Gm14_6,185,611 (LOD = 5.51), and Gm19_44,734,953 (LOD = 6.02), were associated with abundant disease resistance genes, such as
,
,
,
,
,
,
, and
. The annotations of these genes included but not limited to:
class gene,
, cell wall structure,
transporter,
domain, etc. The GWAS based markers showed more accuracies in genomic prediction than the whole genome SNPs, and Bayesian LASSO model was the ideal model in SBR resistance prediction with 44.5% ~ 60.4% accuracies. This study aids breeders in predicting selection accuracy of complex traits such as disease resistance and can shorten the soybean breeding cycle by the identified markers.
The association of microbiome imbalance with cancer development is being one of the research hotspots. Persistent HPV infection is a causal event in cervical cancer initiation, but, little is known ...about the microbiome composition and function in HPV infection. Here we identified the compositional and functional alterations on vaginal samples from 27 HPV16 positive women and 25 age-matched HPV negative controls using shotgun metagenomic sequencing, to provide a comprehensive investigation describing the microbial abundances and enriched metabolic functions in cervicovaginal metagenomes. We further employed qPCR assays to evaluate two selected gene markers of HPV16 infection in an independent validation cohort consisting of 88 HPV16 positive women and 81 controls, and six selected species markers in a subset of validation cohort of 45 HPV16 positive women and 53 controls. We found that the relative abundance of dominant Firmicutes was lower, Actinobacteria, Fusobacteria and viruses phyla were significantly higher in the HPV16-positive group; 77 genera including
, and
were higher, and 20 genera including
and
were lower in the HPV16-positive women. Abundance of 12 genes, 17 genera, and 7 species biomarkers showed an excellent predictive power for the HPV16-positive individuals, with 0.861, 0.819, and 0.918, respectively, of the area under the receiver-operating characteristic curve (AUC). We further characterized the microbial function, and revealed that HPV16-positive women were enriched in metabolism and membrane transport, and depleted by glycan biosynthesis and metabolism, and replication and repair. Quantitative PCR measurements validated that one gene marker and three species were significantly enriched in HPV16-positive women. These results highlight a fundamental fact that there are altered composition and function of the vaginal microbiome in HPV16-positive women, suggesting that vaginal dysbiosis may be associated with HPV infection in the female genital tract.
Aim: The aim of the present study was to investigate the correlation between fibrinogen level, platelet count and prognosis in patients with epithelial ovarian cancer (EOC).
Material and Methods: ...Preoperative fibrinogen level and platelet count in 136 EOC patients and 146 patients with benign ovarian tumor, and their associations with clinicopathologic parameters and survival in EOC patients, were retrospectively analyzed.
Results: The fibrinogen level in EOC was higher than that in benign patients (3.95 ± 1.37 g/L versus 2.88 ± 0.6 g/L, P < 0.001), and 36.0% (49/136) of EOC patients had hyperfibrinogenemia (fibrinogen >4.0 g/L). The platelet count in EOC was higher than that in benign patients (251.5 ± 89.4 × 109/L versus 206.7 ± 49.0 × 109/L P < 0.001), and 7.4% (10/136) of EOC patients had thrombocytosis (platelet count >400 × 109/L). Hyperfibrinogenemia was associated with International Federation of Gynecologists and Obstetricians (FIGO) stage, non‐optimal cytoreduction and poor chemo‐response, but not with histologic type and grade, CA‐125 level, chemotherapy method, and age. EOC patients with advanced disease showed higher rate of elevated thrombocyte count than patients with early disease (30.7% versus 8.3%, P = 0.002). The rate of thrombocytosis was higher in patients with hyperfibrinogenemia than in those with normal fibrinogen (9/10 versus 1/10, P < 0.001). A significant correlation between platelet count and fibrinogen level was observed in EOC patients (P < 0.001). In multivariate analysis, overall survival was influenced by tumor stage (P < 0.001), chemotherapy with taxane (P < 0.001) and fibrinogen level (P = 0.004), and disease‐free survival was only influenced by tumor stage (P < 0.001).
Conclusion: Our findings suggest that hyperfibrinogenemia may be a predictor for poor chemo‐response and have a potential role as independent prognostic factors in EOC patients.