Exosomal circNFIX promotes angiogenesis in ovarian cancer via miR-518a-3p/TRIM44 axis.

Ovarian cancer (OC) is a gynecological cancer with high mortality. OC-derived exosomal circRNAs can regulate angiogenesis. This study aims to explore the role and mechanism of exosomal circRNA nuclear factor I X (CircNFIX) derived from OC cells in angiogenesis. Quantitative real-time polymerase chain reaction was employed to evaluate the levels of circNFIX, miR-518a-3p, and tripartite motif protein 44 (TRIM44) in OC and adjacent tissues. Exosomes from the ovarian surface epithelial cell (HOSEpiC) and OC cells (SKOV3 or OVCAR3) were isolated by differential centrifugation. Exosomes were cocultured with the human umbilical vein endothelial cells (HUVECs). The angiogenesis capacity was analyzed by Tube formation assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays were used to determine the cell viability and migration ability. The dual-luciferase report, RNA immunoprecipitation (RIP), and RNA pull-down assays were applied to validate the gene's interaction. CircNFIX and TRIM44 expression were higher and miR-518a-3p was lower in OC tissues than in the adjacent tissues. Upregulated circNFIX and TRIM44 were significantly correlated with the tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage of OC patients. HUVECs treated OC-derived exosomes had higher proliferation, migration, and angiogenesis capacities than the control group. While OC-derived exosomal circNFIX silencing restrained HUVECs' proliferation, migration, and angiogenesis, compared with the OC-derived exosomes group. OC-derived exosomal circNFIX positively regulated TRIM44 expression by targeting miR-518a-3p in HUVECs. OC-derived exosomal circNFIX promoted angiogenesis by regulating the Janus-activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) pathway via miR-518a-3p/TRIM44 axis in HUVECs.

CircNFIX stimulates the proliferation, invasion, and stemness properties of ovarian cancer cells by enhancing SH3RF3 mRNA stability via binding LIN28B.

We aimed to study the regulatory roles and mechanism of circular nuclear factor IX (circNFIX) in cancer growth and stemness properties of ovarian cancer (OC). CircNFIX and SH3RF3 levels in OC tissues and cells were tested by quantitative real-time PCR. RNase R treatment quantified circNFIX RNA stability. Molecular interaction among circNFIX, LIN28B, and SH3RF3 was predicted by bioinformatics software and validated through RNA immunoprecipitation (RIP) assay. The gain- or loss-experiments of circNFIX on capabilities of metastasis and stemness in vitro were assessed using Cell Counting Kit-8, Transwell, western blot, and sphere-formation assays. CircNFIX and SH3RF3 were markedly elevated in OC tissues and OC cells. Knocking down circNFIX repressed the proliferation, migration, invasion, and stemness properties of A2780 and SKOV3 cells. The RIP assay verified the direct binding relationship between LIN28B, circNFIX, and SH3RF3. Additionally, overexpression of circNFIX elevated the SH3RF3 expression, while this effect was reversed by LIN28B silence. Rescue experiments demonstrated that the overexpression of SH3RF3 reversed the knockdown of circNFIX on OC cells' proliferation, metastasis, and stemness properties. CircNFIX improved the mRNA stability and translation of SH3RF3 via recruiting LIN28B, thus promoting the proliferation, invasion, and stemness properties of OC cells in vitro.

TRIM44 facilitates ovarian cancer proliferation, migration, and invasion by inhibiting FRK.

Ovarian cancer (OC) is the leading cause of gynecologic cancer-related death in the world. Accumulating evidence indicated the important role of TRIM44 in cancer development. However, how TRIM44 displays in OC and the underlying mechanism remained unclear. TRIM44 and FRK expression in OC tissues and cell lines were investigated by western blot and RT-qPCR. Histotype of tissue samples and patients' data were analyzed. Kaplan-Meier Curve was performed to validate the effect of TRIM44. Colony formation assay, MTT assay, Transwell assay, and wound-healing assay were applied to elucidate the function of TRIM44 in OC cells. CHIP assay was used to explore the association between TRIM44 and FRK. Finally, we performed SKOV3 xenografts in Balb/c nude mice to further confirm the involvement of TRIM44 in OC development. We found TRIM44 highly expressed while FRK displayed low expression in OC cell lines and tissues. Moreover, analysis of histotype of tissues and patients' data and Kaplan-Meier Curve implied the important role of TRIM44 and FRK in tumor progression. Further in vitro study suggested that knocking down TRIM44 inhibited OC cells proliferation, migration, and invasion. Besides, FRK was identified as the target gene of TRIM44 in OC, and TRIM44 promoted OC cells proliferation, migration, and invasion by inhibiting FRK. Finally, in vivo animal experiment further confirmed the promotive effect of TRIM44 on OC progression. Our findings demonstrated that TRIM44 facilitated OC proliferation, migration, and invasion by inhibiting FRK, providing new insights for theoretical research and therapy of OC.

Transcriptome changes induced by RUNX3 in cervical cancer cells in vitro.

Runt-related transcription factor 3 (RUNX3) is a member of Runt domain family that is known to play key roles in various different types of tumor. It was recently demonstrated that RUNX3 may also be associated with cervical cancer. The aim of the present study was to investigate the potential association between transcriptome changes and RUNX3 expression in cervical cancer. A RUNX3 overexpression model was constructed using cervical cancer cell lines by RUNX3 plasmid transfection. It was demonstrated that the upregulated expression of RUNX3 inhibited proliferation of cervical cancer cell lines, particularly SiHa cells, and was associated with the expression of the IL-6, PTGS2, FOSL1 and TNF genes. In addition, it was revealed that the TNF and FoxO pathways may also be affected by RUNX3. Therefore, the expression of the RUNX3 gene may be involved in the occurrence and progression of cervical cancer.

Stability Study of Cervical Specimens Collected by Swab and Stored Dry Followed by Human Papillomavirus DNA Detection Using the cobas 4800 Test.

Safer, more convenient methods for cervical sample collection and storage are necessary to facilitate human papillomavirus (HPV) DNA testing in low-resource settings. Our study aimed to evaluate the stability of cervical specimens collected with dry swabs and stored dry, compared to liquid-based cytology (LBC) samples, as detected by HPV DNA testing. Women with abnormal cytological findings or HPV-positive results at colposcopy were recruited from the West China Second University Hospital, Sichuan University, between October 2013 and March 2014. From each woman, physicians collected cervical specimens with a swab placed into a Sarstedt tube and a CytoBrush placed into LBC medium. Samples were randomly assigned to be stored at uncontrolled ambient temperature for 2, 7, 14, or 28 days and then were tested for 14 high-risk HPV (HR-HPV) types using the cobas HPV test. The rates of agreement between dry swab and LBC samples for any HR-HPV type, HPV16, HPV18, and the 12 pooled HR-HPV types were 93.8%, 97.8%, 99.4%, and 93.2%, respectively, with kappa values of 0.87 (95% confidence interval [CI], 0.83 to 0.91), 0.94 (95% CI, 0.91 to 0.97), 0.94 (95% CI, 0.87 to 1.00), and 0.86 (95% CI, 0.82 to 0.90). The performance of swab samples for detection of cervical precancerous lesions by means of cobas HPV testing was equal to that of LBC samples, even with stratification by storage time. Dry storage of swab-collected cervical samples can last for 1 month without loss of test performance by cobas HPV testing, compared to LBC samples, which may offer a simple inexpensive approach for cervical cancer screening in low-resource settings.

Clinical Significance of Serum Interleukin-31 and Interleukin-33 Levels in Patients of Endometrial Cancer: A Case Control Study.

Aims. Previous evidence has proved that interleukin-31 (IL-31) and interleukin-33 (IL-33) can be potential markers in some cancers' formulation. We aimed to determine the potential role of IL-31 and IL-33 in prognosis of endometrial cancer patients. Methods. Serum samples were collected from 160 patients with endometrial cancer and 160 healthy controls. The ELISA kits (Raybio® Systems) specific for human IL-31 and human IL-33 were used. Serum levels of tumor markers (CEA, CA-125, and CA19-9) were measured by chemiluminescence immunoassay. A two-side P value < 0.05 was indicated to be significant. Results. Serum levels of IL-31 and IL-33 in patients were significantly elevated compared to those of healthy controls. The interleukin levels were also related to clinical characteristics, including tumor stages, depth of invasion, and existence of node metastases and distant metastases. The sensitivity and specificity of IL-31 and IL-33 were higher than the counterparts of tumor markers, both separately and in combination of IL-31, IL-33, and the clinical markers. Conclusions. This report is the first one mentioning the possible association between serum IL-31 and IL-33 and endometrial cancer. With their sensitivity and specificity, the interleukins may be useful biomarkers for endometrial cancer's prognosis.

Advances in the research of genetic engineering of heavy metal resistance and accumulation in plants / 生物工程学报

Using plants to remove or inactivate heavy metal pollutants from soils and surface waters provide a cheap and sustainable approach of Phytoremediation. However, field trials suggested that the efficiency of contaminant removal using natural hyperaccumulators is insufficient, due to that many of these species are slow growing and produce little shoot biomass. These factors severely constrain their potential for large-scale decontamination of polluted soils. Moreover, both the micronutrient and toxic metal content accumulated in crops determine the quality and safety of our food-chain. By a transgenic approach, the introduction of novel genes responsible for hyperaccumulating phenotype into high biomass plants and/or stable crops uptaking minerals as food is a promising strategy for the development of effective techniques of phytoremediation and improvement of nutritional value of stable food through a viable commercialization. Recently, the progress at molecular level for heavy metal uptaking, detoxification and hyperaccumulation in plants, and also the clarification of some functional genes in bacteria, yeasts, plants and animals, have advanced the research on genetic engineering plants of heavy metal resistance and accumulation, and on the functional genes (e . g. gsh1, MerA and ArsC) and their genetic transformated plants. These studies demonstrated commercialization potentials of phytoremediation. In this paper, the molecular approach, effects and problems in gene transformation were discussed in details, and also the strategy and emphases were probed into the future research.