ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma.

BACKGROUND: Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified. METHODS: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression. RESULTS: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/ß-catenin pathway, promoting malignant behaviors in EC cells. CONCLUSION: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/ß-catenin pathway underlines its potential as a therapeutic target.

Nomograms predicting the overall survival and cancer-specific survival of patients with stage IIIC1 cervical cancer.

BACKGROUND: To explore the factors that affect the prognosis of overall survival (OS) and cancer-specific survival (CSS) of patients with stage IIIC1 cervical cancer and establish nomogram models to predict this prognosis. METHODS: Data from patients in the Surveil-lance, Epidemiology, and End Results (SEER) programme meeting the inclusion criteria were classified into a training group, and validation data were obtained from the First Affiliated Hospital of Anhui Medical University from 2010 to 2019. The incidence, Kaplan-Meier curves, OS and CSS of patients with stage IIIC1 cervical cancer in the training group were evaluated. Nomograms were established according to the results of univariate and multivariate Cox regression models. Harrell's C-index, calibration plots, receiver operating characteristic (ROC) curves and decision-curve analysis (DCA) were calculated to validate the prediction models. RESULTS: The incidence of pelvic lymph node metastasis, a high-risk factor for the prognosis of cervical cancer, decreased slightly over time. Eight independent prognostic variables were identified for OS, including age, race, marriage status, histology, extension range, tumour size, radiotherapy and surgery, but only seven were identified for CSS, with marriage status excluded. Nomograms of OS and CSS were established based on the results. The C-indexes for the nomograms of OS and CSS were 0.687 and 0.692, respectively, using random sampling of SEER data sets and 0.701 and 0.735, respectively, using random sampling of external data sets. The AUCs for the nomogram of OS were 0.708 and 0.705 for the SEER data sets and 0.750 and 0.750 for the external data sets, respectively. In addition, AUCs of 0.707 and 0.709 were obtained for the nomogram of CSS when validated using SEER data sets, and 0.788 and 0.785 when validated using external data sets. Calibration plots for the nomograms were almost identical to the actual observations. The DCA also indicated the value of the two models. CONCLUSIONS: Eight independent prognostic variables were identified for OS. The same factors predicted CSS, with the exception of the marriage status. Both OS and CSS nomograms had good predictive and clinical application value after validation. Notably, tumour size had the largest contribution to the OS and CSS nomograms.

Paleo-polyploidization in Lycophytes.

Lycophytes and seed plants constitute the typical vascular plants. Lycophytes have been thought to have no paleo-polyploidization although the event is known to be critical for the fast expansion of seed plants. Here, genomic analyses including the homologous gene dot plot analysis detected multiple paleo-polyploidization events, with one occurring approximately 13-15 million years ago (MYA) and another about 125-142 MYA, during the evolution of the genome of Selaginella moellendorffii, a model lycophyte. In addition, comparative analysis of reconstructed ancestral genomes of lycophytes and angiosperms suggested that lycophytes were affected by more paleo-polyploidization events than seed plants. Results from the present genomic analyses indicate that paleo-polyploidization has contributed to the successful establishment of both lineages-lycophytes and seed plants-of vascular plants.

Deciphering the high-quality genome sequence of coriander that causes controversial feelings.

Coriander (Coriandrum sativum L. 2n = 2x = 22), a plant from the Apiaceae family, also called cilantro or Chinese parsley, is a globally important crop used as vegetable, spice, fragrance and traditional medicine. Here, we report a high-quality assembly and analysis of its genome sequence, anchored to 11 chromosomes, with total length of 2118.68 Mb and N50 scaffold length of 160.99 Mb. We found that two whole-genome duplication events, respectively, dated to ~45-52 and ~54-61 million years ago, were shared by the Apiaceae family after their split from lettuce. Unbalanced gene loss and expression are observed between duplicated copies produced by these two events. Gene retention, expression, metabolomics and comparative genomic analyses of terpene synthase (TPS) gene family, involved in terpenoid biosynthesis pathway contributing to coriander's special flavour, revealed that tandem duplication contributed to coriander TPS gene family expansion, especially compared to their carrot counterparts. Notably, a TPS gene highly expressed in all 4 tissues and 3 development stages studied is likely a major-effect gene encoding linalool synthase and myrcene synthase. The present genome sequencing, transcriptome, metabolome and comparative genomic efforts provide valuable insights into the genome evolution and spice trait biology of Apiaceae and other related plants, and facilitated further research into important gene functions and crop improvement.

Cervical invasion, lymphovascular space invasion, and ovarian metastasis as predictors of lymph node metastasis and poor outcome on stages I to III endometrial cancers: a single-center retrospective study.

BACKGROUND: The aim of this study is to determine pathological factors that increase the risk of LNM and indicate poor survival of patients diagnosed with endometrial cancer and treated with surgical staging. METHOD: Between January 2010 and November 2018, we enrolled 874 eligible patients who received staging surgery in the First Affiliated Hospital of Anhui Medical University. The roles of prognostic risk factors, such as age, histological subtype, tumor grade, myometrial infiltration, tumor diameter, cervical infiltration, lymphopoiesis space invasion (LVSI), CA125, and ascites, were evaluated. Multivariable logistic regression models were used to identify the predictors of LNM. Kaplan-Meier and COX regression models were utilized to study the overall survival. RESULTS: Multivariable regression analysis confirmed cervical stromal invasion (OR 3.412, 95% CI 1.631-7.141; P < 0.01), LVSI (OR 2.542, 95% CI 1.061-6.004; P = 0.04) and ovarian metastasis (OR 6.236, 95% CI 1.561-24.904; P = 0.01) as significant predictors of nodal dissemination. Furthermore, pathological pattern (P = 0.03), myometrial invasion (OR 2.70, 95% CI 1.139-6.40; P = 0.01), and lymph node metastasis (OR 9.675, 95% CI 3.708-25.245; P < 0.01) were independent predictors of decreased overall survival. CONCLUSIONS: Cervical invasion, lymphopoiesis space invasion, and ovarian metastasis significantly convey the risk of LNM. Pathological type, myometrial invasion, and lymph node metastasis are all important predictors of survival and should be scheduled for completion when possible in the surgical staging procedure.

Long Noncoding RNA HOTAIR Promotes Endometrial Carcinoma Cell Proliferation by Binding to PTEN via the Activating Phosphatidylinositol 3-Kinase/Akt Signaling Pathway.

Accumulating evidence has demonstrated that long noncoding RNAs (lncRNAs) exert essential biological functions in modulating the progression of endometrial carcinoma (EC). HOX transcript antisense intergenetic RNA (HOTAIR) has been widely recognized as a crucial mediator in various tumors, including EC. However, the specific molecular mechanism of HOTAIR in the development of EC remains to be further explored. In the present study, we demonstrated that HOTAIR was significantly upregulated in EC tissues; this was negatively correlated with PTEN but positively correlated with phosphatidylinositol 3-kinase (PI3K) and Akt. Overexpression of HOTAIR promoted proliferation and inhibited apoptosis of EC cells, similar to PTEN knockdown. Additionally, RNA pulldown demonstrated the direct binding relationship between HOTAIR and PTEN. Furthermore, HOTAIR activated the PI3K/Akt pathway to promote EC progression by suppressing PTEN in vivo Taking these results together, we revealed that high expression of HOTAIR promoted cell proliferation and inhibited apoptosis through activating the PI3K/Akt pathway via binding to PTEN, which might provide a prognostic marker and therapeutic target of EC.

Alignment of Rutaceae Genomes Reveals Lower Genome Fractionation Level Than Eudicot Genomes Affected by Extra Polyploidization.

Owing to their nutritional and commercial values, the genomes of several citrus plants have been sequenced, and the genome of one close relative in the Rutaceae family, atalantia (Atalantia buxifolia), has also been sequenced. Here, we show a family-level comparative analysis of Rutaceae genomes. By using grape as the outgroup and checking cross-genome gene collinearity, we systematically performed a hierarchical and event-related alignment of Rutaceae genomes, and produced a gene list defining homologous regions based on ancestral polyploidization or speciation. We characterized genome fractionation resulting from gene loss or relocation, and found that erosion of gene collinearity could largely be described by a geometric distribution. Moreover, we found that well-assembled Rutaceae genomes retained significantly more genes (65-82%) than other eudicots affected by recursive polyploidization. Additionally, we showed divergent evolutionary rates among Rutaceae plants, with sweet orange evolving faster than others, and by performing evolutionary rate correction, re-dated major evolutionary events during their evolution. We deduced that the divergence between the Rutaceae family and grape occurred about 81.15-91.74 million years ago (mya), while the split between citrus and atalantia plants occurred <10 mya. In addition, we showed that polyploidization led to a copy number expansion of key gene families contributing to the biosynthesis of vitamin C. Overall, the present effort provides an important comparative genomics resource and lays a foundation to understand the evolution and functional innovation of Rutaceae genomes.

Two Likely Auto-Tetraploidization Events Shaped Kiwifruit Genome and Contributed to Establishment of the Actinidiaceae Family.

The genome of kiwifruit (Actinidia chinensis) was sequenced previously, the first in the Actinidiaceae family. It was shown to have been affected by polyploidization events, the nature of which has been elusive. Here, we performed a reanalysis of the genome and found clear evidence of 2 tetraploidization events, with one occurring ∼50-57 million years ago (Mya) and the other ∼18-20 Mya. Two subgenomes produced by each event have been under balanced fractionation. Moreover, genes were revealed to express in a balanced way between duplicated copies of chromosomes. Besides, lowered evolutionary rates of kiwifruit genes were observed. These findings could be explained by the likely auto-tetraploidization nature of the polyploidization events. Besides, we found that polyploidy contributed to the expansion of key functional genes, e.g., vitamin C biosynthesis genes. The present work also provided an important comparative genomics resource in the Actinidiaceae and related families.