The role of MicroRNA molecules and MicroRNA-regulating machinery in the pathogenesis and progression of epithelial ovarian cancer

MicroRNA molecules are small, single-stranded RNA molecules that function to regulate networks of genes. They play important roles in normal female reproductive tract biology, as well as in the pathogenesis and progression of epithelial ovarian cancer. DROSHA, DICER, and Argonaute proteins are components of the microRNA-regulatory machinery and mediate microRNA production and function. This review discusses aberrant expression of microRNA molecules and microRNA-regulating machinery associated with clinical features of epithelial ovarian cancer. Understanding the regulation of microRNA molecule production and function may facilitate the development of novel diagnostic and therapeutic strategies to improve the prognosis of women with epithelial ovarian cancer. Additionally, understanding microRNA molecules and microRNA-regulatory machinery associations with clinical features may influence prevention and early detection efforts

Unique Molecular Features in High-Risk Histology Endometrial Cancers

Endometrial cancer is the most common gynecologic malignancy in the United States and the sixth most common cancer in women worldwide. Fortunately, most women who develop endometrial cancer have low-grade early-stage endometrioid carcinomas, and simple hysterectomy is curative. Unfortunately, 15% of women with endometrial cancer will develop high-risk histologic tumors including uterine carcinosarcoma or high-grade endometrioid, clear cell, or serous carcinomas. These high-risk histologic tumors account for more than 50% of deaths from this disease. In this review, we will highlight the biologic differences between low- and high-risk carcinomas with a focus on the cell of origin, early precursor lesions including atrophic and proliferative endometrium, and the potential role of stem cells. We will discuss treatment, including standard of care therapy, hormonal therapy, and precision medicine-based or targeted molecular therapies. We will also discuss the impact and need for model systems. The molecular underpinnings behind this high death to incidence ratio are important to understand and improve outcomes

Uterine Epithelial Development and Enhancer of Zeste Homolog 2: It Is Important for More than Just Cancer

This commentary highlights the article by Fang et al that describes the role of enhancer of zeste homolog 2 in endometrial development

Deletion of Arid1a in Reproductive Tract Mesenchymal Cells Reduces Fertility in Female Mice

Women with endometriosis can suffer from decreased fecundity or complete infertility via abnormal oocyte function or impaired placental-uterine interactions required for normal pregnancy establishment and maintenance. Although AT-rich interactive domain 1A (SWI-like) (ARID1A) is a putative tumor suppressor in human endometrial cancers and endometriosis-associated ovarian cancers, little is known about its role in normal uterine function. To study the potential function of ARID1A in the female reproductive tract, we generated mice with a conditional knockout of Arid1a using anti-Müllerian hormone receptor 2-Cre Female Arid1a conditional knockout mice exhibited a progressive decrease in number of pups per litter, with a precipitous decline after the second litter. We observed no tumors in virgin mice, although one knockout mouse developed a uterine tumor after pregnancy. Unstimulated virgin female knockout mice showed normal oviductal, ovarian, and uterine histology. Uteri of Arid1a knockout mice showed a normal decidualization response and appropriate responses to estradiol and progesterone stimulation. In vitro studies using primary cultures of human endometrial stromal fibroblasts revealed that small interfering RNA knockdown of ARID1A did not affect decidualization in vitro. Timed pregnancy studies revealed the significant resorption of embryos at Embryonic Day 16.5 in knockout mice in the third pregnancy. In addition to evidence of implantation site hemorrhage, pregnant Arid1a knockout mice showed abnormal placental morphology. These results suggest that Arid1a supports successful pregnancy through its role in placental function

MicroRNA-451 suppresses tumor cell growth by down-regulating IL6R gene expression

The miR-451 was found to be frequently down-regulated in tumors, indicating that miR-451 could play an important role in carcinogenesis. This study uncovered the mechanism by which the miR-451 functions as a tumor suppressor. The target genes of miR-451 were determined using target gene prediction softwares. Then the miR-451 mimics were introduced into RKO and Hela cells respectively. The proliferation and invasion of cells were monitored by MTT, cell cycle and in vitro extracellular matrix invasion assays. Also the angiogenesis of HUVEC cells transfected with miR-451 mimics was examined. Subsequently, IL6R, a predicted target gene of miR-451, was studied by real time PCR, Western blotting, and siRNA technologies. The mRNA and protein levels of IL6R gene were found to be down-regulated in the RKO and Hela cells transfected with miR-451 mimics. Consequently, the cell proliferation was inhibited. Also, the invasion of RKO cells was suppressed. Furthermore, the angiogenesis of HUVEC cells transfected with miR-451 mimics was assayed and the decreased angiogenic ability was detected compared to the controls. All these results were validated by IL6R siRNA experiments. The IL6R gene is a target gene of miR-451. The miR-451 behaves as a tumor suppressor, probably by targeting the IL6R pathway.This project was supported by the Huazhong University of Science and Technology (2010MS034 and HF-09-37-2011-510).Ritrýnt tímaritPeer Reviewe

Universal RNA editing in a human liver at the fetal stage

It is known that RNA editing occurs in human cells, which can change the information transmission from DNA to RNA and proteins. Most previous studies have focused on editing of the mRNAs. Here we reported that several kinds of RNAs, including miRNA, rRNA, mRNA, miscRNA and unknown RNA, exhibited base editing in a human fetal liver. Several editing types are displayed. Our data reveals that RNA editing may occur in different species of RNAs.This study was supported by the Huazhong University of Science and Technology (2010MS034).Peer Reviewe

Translational Applications of Linear and Circular Long Noncoding RNAs in Endometriosis

Endometriosis is a chronic gynecologic disease that negatively affects the quality of life of many women. Unfortunately, endometriosis does not have a cure. The current medical treatments involve hormonal manipulation with unwanted side effects and high recurrence rates after stopping the medication. Sadly, a definitive diagnosis for endometriosis requires invasive surgical procedures, with the risk of complications, additional surgeries in the future, and a high rate of recurrence. Both improved therapies and noninvasive diagnostic tests are needed. The unique molecular features of endometriosis have been studied at the coding gene level. While the molecular components of endometriosis at the small RNA level have been studied extensively, other noncoding RNAs, such as long intergenic noncoding RNAs and the more recently discovered subset of long noncoding RNAs called circular RNAs, have been studied more limitedly. This review describes the molecular formation of long noncoding and the unique circumstances of the formation of circular long noncoding RNAs, their expression and function in endometriosis, and promising preclinical studies. Continued translational research on long noncoding RNAs, including the more stable circular long noncoding RNAs, may lead to improved therapeutic and diagnostic opportunities

Comparative genomic analysis of C4 photosynthetic pathway evolution in grasses

Comparison of the sorghum, maize and rice genomes shows that gene duplication and functional innovation is common to evolution of most but not all genes in the C4 photosynthetic pathwa

Origination, Expansion, Evolutionary Trajectory, and Expression Bias of AP2/ERF Superfamily in Brassica napus

The AP2/ERF superfamily, one of the most important transcription factor families, plays crucial roles in response to biotic and abiotic stresses. So far, a comprehensive evolutionary inference of its origination and expansion has not been available. Here, we identified 515 AP2/ERF genes in B. napus, a neo-tetraploid forming ~7500 years ago, and found that 82.14% of them were duplicated in the tetraploidization. A prominent subgenome bias was revealed in gene expression, tissue-specific, and gene conversion. Moreover, a large-scale analysis across plants and alga suggested that this superfamily could have been originated from AP2 family, expanding to form other families (ERF, and RAV). This process was accompanied by duplicating and/or alternative deleting AP2 domain, intragenic domain sequence conversion, and/or by acquiring other domains, resulting in copy number variations, alternatively contributing to functional innovation. We found that significant positive selection occurred at certain critical nodes during the evolution of land plants, possibly responding to changing environment. In conclusion, the present research revealed origination, functional innovation, and evolutionary trajectory of the AP2/ERF superfamily, contributing to understanding their roles in plant stress tolerance

Statistical inference of chromosomal homology based on gene colinearity and applications to Arabidopsis and rice

BACKGROUND: The identification of chromosomal homology will shed light on such mysteries of genome evolution as DNA duplication, rearrangement and loss. Several approaches have been developed to detect chromosomal homology based on gene synteny or colinearity. However, the previously reported implementations lack statistical inferences which are essential to reveal actual homologies. RESULTS: In this study, we present a statistical approach to detect homologous chromosomal segments based on gene colinearity. We implement this approach in a software package ColinearScan to detect putative colinear regions using a dynamic programming algorithm. Statistical models are proposed to estimate proper parameter values and evaluate the significance of putative homologous regions. Statistical inference, high computational efficiency and flexibility of input data type are three key features of our approach. CONCLUSION: We apply ColinearScan to the Arabidopsis and rice genomes to detect duplicated regions within each species and homologous fragments between these two species. We find many more homologous chromosomal segments in the rice genome than previously reported. We also find many small colinear segments between rice and Arabidopsis genomes