Tripartite-motif 3 represses ovarian cancer progression by downregulating lactate dehydrogenase A and inhibiting AKT signaling.

The E3 ubiquitin ligase Tripartite-motif 3 (TRIM3) is known to play a crucial role in tumor suppression in various tumors through different mechanisms. However, its function and mechanism in ovarian cancer have yet to be elucidated. Our study aims to investigate the expression of TRIM3 in ovarian cancer and evaluate its role in the development of the disease. Our findings revealed a significant decrease in TRIM3 mRNA and protein levels in ovarian cancer tissues and cells when compared to normal ovarian epithelial tissues and cells. Furthermore, we observed a negative correlation between the protein level of TRIM3 and the FIGO stage, as well as a positive correlation with the survival of ovarian cancer patients. Using gain and loss of function experiments, we demonstrated that TRIM3 can inhibit cell proliferation, migration and invasion of the ovarian cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistic studies showed that TRIM3 interacts with lactate dehydrogenase A, a key enzyme in the glycolytic pathway, through its B-box and coiled-coil domains and induces its ubiquitination and proteasomal degradation, leading to the inhibition of glycolytic ability in ovarian cancer cells. RNA-sequencing analysis revealed significant alterations in the phosphatidylinositol signaling pathways upon TRIM3 overexpression. Additionally, overexpression of TRIM3 inhibited the phosphorylation of AKT. In conclusion, our study demonstrated that TRIM3 exerts a tumor-suppressive effect in ovarian cancer, at least partially, by downregulating LDHA and inhibiting the AKT signaling pathway, and thus leading to the inhibition of glycolysis and limiting the growth of ovarian cancer cells.

LncRNA IDH1-AS1 sponges miR-518c-5p to suppress proliferation of epithelial ovarian cancer cell by targeting RMB47.

Long noncoding RNA (lncRNA) IDH1 antisense RNA 1 ( IDH1-AS1) is involved in the progression of multiple cancers, but its role in epithelial ovarian cancer (EOC) is unknown. Therefore, we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR (qPCR). We first evaluated the effects of IDH1-AS1 on the proliferation, migration, and invasion of EOC cells through cell counting kit-8, colony formation, EdU, transwell, wound-healing, and xenograft assays. We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter, qPCR, rescue experiments, and Western blotting. We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells. High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis, because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC. IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation. The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression. Furthermore, we found that RNA binding motif protein 47 (RBM47) was the downstream target of miR-518c-5p, that upregulation of RBM47 inhibited EOC cell proliferation, and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown. Taken together, IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.

LncRNA SLC25A21-AS1 increases the chemosensitivity and inhibits the progression of ovarian cancer by upregulating the expression of KCNK4.

Owing to high mortality rate, ovarian cancer seriously threatens women's health. Extensive abdominal metastasis and chemoresistance are the leading causes of ovarian cancer deaths. Through lncRNA sequencing, our previous study identified lncRNA SLC25A21-AS1, which was significantly downregulated in chemoresistant ovarian cancer cells. In this study, we aimed to evaluate the role and mechanism of SLC25A21-AS1 in ovarian cancer. The expression of SLC25A21-AS1 was analyzed by qRT-PCR and online database GEPIA. The biological functions of SLC25A21-AS1 and KCNK4 were analyzed by CCK-8, transwell, and flow cytometry. The specific mechanism was analyzed by RNA-sequencing, RNA binding protein immunoprecipitation, rescue experiments, and bioinformatic analysis. SLC25A21-AS1 was decreased in ovarian cancer tissues and cell lines. Overexpression of SLC25A21-AS1 enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin, and inhibited cell proliferation, invasion, and migration, while SLC25A21-AS1-silencing showed the opposite effect. Potassium channel subfamily K member 4 (KCNK4) was significantly up-regulated upon enforced expression of SLC25A21-AS1. Overexpression of KCNK4 inhibited cell proliferation, invasion, migration ability, and enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin. Meanwhile, KNCK4-overexpression rescued the promotive effect of SLC25A21-AS1-silencing on cell proliferation, invasion and migration. In addition, SLC25A21-AS1 could interact with the transcription factor Enhancer of Zeste Homolog 2 (EZH2), while EZH2 knockdown increased the expression of KCNK4 in some of the ovarian cancer cell lines. SLC25A21-AS1 enhanced the chemosensitivity and inhibited the proliferation, migration, and invasion ability of ovarian cancer cells at least partially by blocking EZH2-mediated silencing of KCNK4.

Friend and foe: the regulation network of ascites components in ovarian cancer progression.

The tumor microenvironment (TME) and its complex role in cancer progression have been hotspots of cancer research in recent years. Ascites, which occurs frequently in patients with ovarian cancer especially in advanced stages, represents a unique TME. Malignant ascites contains abundant cellular and acellular components that play important roles in tumorigenesis, growth, metastasis, and chemoresistance of ovarian cancer through complex molecular mechanisms and signaling pathways. As a valuable liquid biopsy sample, ascites fluid is also of great significance for the prognostic analysis of ovarian cancer. The components of ovarian cancer ascites are generally considered to comprise tumor-promoting factors; however, in recent years studies have found that ascites also contains tumor-suppressing factors, raising new perspectives on interactions between ascites and tumors. Malignant ascites directly constitutes the ovarian cancer microenvironment, therefore, the study of its components will aid in the development of new therapeutic strategies. This article reviews the current research on tumor-promoting and tumor-suppressing factors and molecular mechanisms of their actions in ovarian cancer-derived ascites and therapeutic strategies targeting ascites, which may provide references for the development of novel therapeutic targets for ovarian cancer in the future.

Long noncoding RNA RFPL1S-202 inhibits ovarian cancer progression by downregulating the IFN-ß/STAT1 signaling.

BACKGROUND: RFPL1S was first identified as one of the pseudogenes located in the intrachromosomal duplications within 22q12-13. Our previous study found that one of the predicted transcripts of lncRNA RFPL1S, ENST00000419368.1 (GRCh37/hg19), also named as RFPL1S-202 in Ensembl website, is significantly downregulated in the chemoresistant ovarian cancer cells. However, its function and underlying mechanism have not been studied. METHODS: Quantitative Real-time PCR was used to analyze the expression. Cell Counting Kit-8, transwell, flow cytometry analysis and tail vein injected mouse model were used to test the function. RNA-sequencing, RNA pull down, western blot, ELISA and RNA-Binding Protein Immunoprecipitation were performed for studying the mechanism. 5' and 3' rapid amplification of complementary DNA ends were performed to analyze the full length of RFPL1S-202. RESULTS: RFPL1S-202 is significantly downregulated in epithelial ovarian cancer tissues and cell lines. Gain- and loss-of-function study indicated that RFPL1S-202 could enhance cisplatin or paclitaxel in cytotoxicity, inhibit cell proliferation, invasion and migration of ovarian cancer cells in vitro, and inhibit the liver metastasis of ovarian cancer cells in vivo. Mechanistically, RFPL1S-202 could physically interact with DEAD-Box Helicase 3 X-linked (DDX3X) protein, and decrease the expression of p-STAT1 and the IFN inducible genes by increasing the m6A modification of IFNB1. RFPL1S-202 is a spliced and polyadenylated non-coding RNA with a full length of 1071 bp. CONCLUSIONS: Our study suggested that the predicted lncRNA RFPL1S-202 exerts a tumor- suppressive function in oarian cancer chemoresistance and progression by interacting with DDX3X and down-regulating the IFN-ß-STAT1 signaling pathway.

Peptide PDHPS1 Inhibits Ovarian Cancer Growth through Disrupting YAP Signaling.

The lives of patients with ovarian cancer are threatened largely due to metastasis and drug resistance. Endogenous peptides attract increasing attention in oncologic therapeutic area, a few antitumor peptides have been approved by the FDA for clinical use over the past decades. However, only few peptides or peptide-derived drugs with antiovarian cancer effects have been identified. Here we focused on the biological roles and mechanism of a peptide named PDHPS1 in ovarian cancer development. Our results indicated that PDHPS1 reduced the proliferation ability of ovarian cancer cells in vitro and inhibited the ovarian cancer growth in vivo. Peptide pull down and following mass spectrometry, Western blot and qRT-PCR revealed that PDHPS1 could bind to protein phosphatase 2 phosphatase activator (PTPA), an essential activator of protein phosphatase 2A (PP2A), which resulted in increase of phosphorylated YAP, further inactivated YAP, and suppressed the expression of its downstream target genes. Flow cytometry, cell membrane permeability test, and IHC staining study demonstrated that there were no observable side effects of PDHPS1 on normal ovarian epithelium and hepatorenal function. Besides, modification of membrane penetration could improve the physicochemical properties and biological activity of PDHPS1. In conclusion, our study demonstrated that the endogenous peptide PDHPS1 serves as an antitumor peptide to inhibit YAP signaling pathway though interacting with PTPA in ovarian cancer.

The group-reference effect and soldiers' recognition memory.

Previous research has consistently found that the self-reference effect (SRE) is equal to, or stronger than, the group-reference effect (GRE) for memory performance. The military strongly emphasises group identity; this study investigated whether the GRE was stronger than the SRE for soldiers. Soldiers were recruited to participate in Experiments 1 and Experiment 2. Experiment 1 revealed that recognition was better under the group-reference condition than the self-reference condition. Experiment 2 was identical to Experiment 1, with the exception that the recognition test required participants to use "remember" / "know" / "guess" judgments. The results were consistent with those of Experiment 1, that is, the GRE contributed to better recognition than the SRE, but the difference was statistically significant only for "know" responses. Using a less cohesive group (university students) as participants, Experiment 3 found that the GRE was not superior to the SRE for memory recognition, which indicated that the results of Experiments 1 and 2 were exclusive to soldiers. The findings suggest that soldiers' sense of self might be unique, and that an ingroup sense of self might be dominant for soldiers.

Peptidome characterization of ovarian cancer serum and the identification of tumor suppressive peptide ZYX36-58.

BACKGROUND: Several serum biomarkers, including miRNA, mRNA, protein and peptides in cancer patients are also important mediators of cancer progression. METHODS: The differentially expressed peptides between the serum of ovarian cancer patients and healthy controls were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The function of the peptides was analyzed by CCK8, transwell, wound healing, and flow cytometry analysis. And the mechanism of the peptides was analyzed by peptide pull down, and high-throughput RNA-sequencing. RESULTS: A total of 7 and 46 peptides were significantly up-regulated and down-regulated in the serum of ovarian cancer patients, respectively. The precursor proteins of the differentially expressed peptides mainly involved in the complement and coagulation cascades, platelet activation, phagosome and focal adhesion pathways. Interestingly, focal adhesion, platelet activation, platelet-cancer cell interaction, complement activation, coagulation cascades and phagosome formation are all critical factors for cancer initiation or progression, which indicated that the peptides may play a crucial role in cancer development. And we identified one peptide, ZYX36-58, which was down-regulated in the serum of ovarian cancer patients, significantly inhibited invasion and migration and promoted the apoptosis of ovarian cancer cells. Mechanistic study indicated that ZYX36-58 interacted with and increased the protein level of the antiangiogenic protein thrombospondin-1 (TSP1), which has a tumor suppressive effect on ovarian cancer. CONCLUSIONS: ZYX36-58, which was significantly down-regulated in the serum of ovarian cancer patients can significantly inhibit cell invasion, migration and promote apoptosis of ovarian cancer cells by binding and up-regulating TSP1 protein expression.

Research Progress Evaluating the Function and Mechanism of Anti-Tumor Peptides.

Malignant tumors cause a high mortality rate worldwide, and they severely threaten human health and negatively affect the economy. Despite the advancements in tumor-related molecular genetics and effective new processes in anti-tumor drug development, the anti-tumor drugs currently used in clinical practice are inadequate due to their poor efficacy or severe side effects. Therefore, developing new safe and efficient drugs is a top priority for curing cancer. The peptide has become a suitable agent due to its exact molecular weight between whole protein and small molecule, and it has high targeting ability, high penetrability, low immunogenicity, and is convenient to synthesize and easy to modify. Because of these advantages, peptides have excellent prospect for application as anti-tumor agents. This article reviews the recent research progress evaluating anti-tumor peptides and their anti-tumor mechanisms, and may act as a reference for the future development and clinical application of anti-tumor peptides.

Environmental sustainability of bioethanol produced from sweet sorghum stem on saline-alkali land.

Life cycle assessment was conducted to evaluate the energy efficiency and environmental impacts of a bioethanol production system that uses sweet sorghum stem on saline-alkali land as feedstock. The system comprises a plant cultivation unit, a feedstock transport unit, and a bioethanol conversion unit, with 1000L of bioethanol as a functional unit. The net energy ratio is 3.84, and the net energy gain is 17.21MJ/L. Agrochemical production consumes 76.58% of the life cycle fossil energy. The category with the most significant impact on the environment is eutrophication, followed by acidification, fresh water aquatic ecotoxicity, human toxicity, and global warming. Allocation method, waste recycling approach, and soil salinity significantly influence the results. Using vinasse to produce pellet fuel for steam generation significantly improves energy efficiency and decreases negative environmental impacts. Promoting reasonable management practices to alleviate saline stress and increasing agrochemical utilization efficiency can further improve environmental sustainability.