KRAS, YWHAE, SP1 and MSRA as biomarkers in endometrial cancer.

BACKGROUND: We demonstrated that drinking hydrogen-rich water (HRW) inhibits endometrial tumor growth in our previous work. This research is to identify differentially expressed proteins (DEPs) between HRW and purified water groups in a xenograft mouse model of endometrial cancer (EC). METHODS: Samples were analyzed using tandem mass tags (TMTs) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). DEPs were identified using bioinformatics to determine potential molecular functions and immunohistochemical (IHC) staining. RESULTS: In total, 11 DEPs were identified in the HRW group relative to the control. The up-regulated proteins included Gatad1, Ttyh3, Nek4, Dyrk2, and Gimap1, while the down-regulated proteins included SP1, Msl1, Plekha7, Dtwd2, MSRA, and KRAS. Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were associated with the binding region, biological regulation, endocrine resistance, estrogen signaling, choline metabolism in cancer and human cytomegalovirus infection. Furthermore, network analysis indicated that KRAS and MSRA interact with YWHAE. KRAS, YWHAE and SP1 were strongly expressed, while MSRA was weak expressed in atypical hyperplasia and EC tissue as well as in HRW group in xenograft tumor tissue. CONCLUSIONS: KRAS, YWHAE, SP1 and MSRA might be regarded as focused biomarkers to assess the prognosis of EC.

Promising advancement in fermentative succinic acid production by yeast hosts.

As a platform chemical with various applications, succinic acid (SA) is currently produced by petrochemical processing from oil-derived substrates such as maleic acid. In order to replace the environmental unsustainable hydrocarbon economy with a renewable environmentally sound carbohydrate economy, bio-based SA production process has been developed during the past two decades. In this review, recent advances in the valorization of solid organic wastes including mixed food waste, agricultural waste and textile waste for efficient, green and sustainable SA production have been reviewed. Firstly, the application, market and key global players of bio-SA are summarized. Then achievements in SA production by several promising yeasts including Saccharomyces cerevisiae and Yarrowia lipolytica are detailed, followed by calculation and comparison of SA production costs between oil-based substrates and raw materials. Lastly, challenges in engineered microorganisms and fermentation processes are presented together with perspectives on the development of robust yeast SA producers via genome-scale metabolic optimization and application of low-cost raw materials as fermentation substrates. This review provides valuable insights for identifying useful directions for future bio-SA production improvement.

Downregulation of miR-145-5p in cancer cells and their derived exosomes may contribute to the development of ovarian cancer by targeting CT.

The present study aimed to identify shared microRNAs (miRNAs) in ovarian cancer (OC) cells and their exosomes using microarray data (accession number GSE103708) available from the Gene Expression Omnibus database, including exosomal samples from 13 OC cell lines and 3 normal ovarian surface epithelial cell lines, and their original cell samples. Differentially expressed miRNAs (DE­miRNAs) were identified using the Linear Models for Microarray data method, and mRNA targets of DE­miRNAs were predicted using the miRWalk2 database. The potential functions of target genes were analyzed using Database for Annotation, Visualization and Integrated Discovery and intersected with known OC­associated pathways downloaded from the Comparative Toxicogenomics Database. The associations between crucial miRNAs and target genes, and their clinical associations, were validated using data from The Cancer Genome Atlas. As a result, 16 upregulated and 6 downregulated DE­miRNAs were shared in OC cell lines and their exosomes compared with normal controls. The target genes of 11 common DE­miRNAs were predicted. Among these DE­miRNAs, a low expression of homo sapiens (hsa)­miR­145­5p was significantly correlated with a poor prognosis and higher stages. Although 91 target genes were predicted for hsa­miR­145­5p, only 4 genes [connective tissue growth factor (CTGF), myotubularin­related protein 14, protein phosphatase 3 catalytic subunit alpha and suppressor of cytokine signaling 7] were suggested as risk factors for prognosis. The subsequent Pearson's correlation analysis validated a significant negative correlation between hsa­miR­145­5p and CTGF (r=­0.1126, P=0.02188). According to the results of the functional analysis, CTGF is involved in the Hippo signaling pathway (hsa04390). In conclusion, decreased expression of hsa­miR­145 in OC and OC­derived exosomes may be a crucial biomarker for the diagnosis and treatment of OC.

Identification of exosomal and non­exosomal microRNAs associated with the drug resistance of ovarian cancer.

MicroRNAs (miRNAs) serve important roles in drug­resistance; however, exosomal miRNAs associated with drug­resistance in ovarian cancer (OC) have not been reported to date. The current study aimed to analyze the drug resistance­associated exosomal miRNAs in original OC cells and their derived exosomes using microarray data downloaded from the Gene Expression Omnibus database (series GSE76449). The chemosensitive OC cell lines SKOV3_ip1, A2780_PAR and HEYA8, as well as the chemoresistant cell lines SKOV3_TR, A2780_CP20 and HEYA8_MDR, were investigated. Differentially expressed miRNAs (DE­miRNAs) were identified using the limma method, and their mRNA targets were predicted using the miRWalk and LinkedOmics database. Functions of target genes were analyzed with DAVID tool, while TCGA data were used to explore the survival association of identified miRNAs. According to the results, 28 DE­miRNAs were found to be common in exosomal and original samples of A2780_CP20 cells, among which the functions of 5 miRNAs were predicted (including miR­146b­5p, miR­509­5p, miR­574­3p, miR­574­5p and miR­760). In addition, 16 and 35 DE­miRNAs were detected for HEYA8_MDR and SKOV3_TR, respectively, with the functions of 4 of these miRNAs predicted for each cell line (HEYA8_MDR: miR­30a­3p, miR­30a­5p, miR­612 and miR­617; SKOV3_TR: miR­193a­5p, miR­423­3p, miR­769­5p and miR­922). It was also reported that miR­183­5p was the only one common miRNA among the three cell lines. Furthermore, miR­574­3p, miR­30a­5p and miR­922 may regulate CUL2 to mediate HIF­1 cancer signaling pathway, while miR­183­5p may modulate MECP2, similar to miR­760, miR­30a­5p and miR­922, to influence cell proliferation. Finally, the downregulated miR­612 may promote the expression of TEAD3 via the Hippo signaling pathway, and this miRNA was associated with poor prognosis. In conclusion, the findings of the present study suggested several underlying miRNA targets for improving the chemotherapy sensitivity of OC.

miR­107­5p promotes tumor proliferation and invasion by targeting estrogen receptor­α in endometrial carcinoma.

The aberrant expression of miR107­5p is closely related to the development of several types of human cancers. However, the role of miR­107­5p in endometrial carcinoma (EC) has not been fully confirmed. In the present study, we aimed to explore the function of miR­107­5p in EC carcinogenesis. EC samples and normal endometrial tissues were obtained by laser capture microdissection. It was determined that the expression of miR­107­5p in EC was significantly higher than that in normal endometrium, and higher miR­107­5p expression was related to advanced FIGO stages, lymph node metastasis and myometrial invasion in EC patients. Blocking miR­107­5p significantly inhibited cell proliferation, migration and invasion of EC cells in vitro and in vivo. The results of bioinformatic algorithms and luciferase reporter assays revealed that estrogen receptor α (ERα) was a direct target of miR­107­5p. miR­107­5p downregulated the expression of ERα mRNA and protein. In conclusion, our results highlighted that miR­107­5p is a novel prognostic factor that targets ERα to promote tumor proliferation and invasion of EC.