Circular RNA Eps15-homology domain-containing protein 2 induce resistance of renal cell carcinoma to sunitinib via microRNA-4731-5p/ABCF2 axis.

Circular RNAs (circRNAs) are linked with the occurrence and progression of renal cell carcinoma (RCC). However, circRNAs' mechanism in developing resistance to RCC has not been clarified. This research assessed the role and mechanism of circular RNA circ Eps15-homology domain-containing protein 2 (EHD2) in the resistance of sunitinib (SU) to RCC. ACHN, 786-O, 769P, and HEK-293 T cells and RCC tissue samples were used for the investigations. The circEHD2 expression in RCC cells and tissues was determined through RT-qPCR. Association of circEHD2 with RCC histological grade of RCC was done through Chi-square. MiR-4731-5p, ABCF2, and circEHD2 were transfected into RCC cell lines. A dual-luciferase reporter assay was used to determine the interaction between miR-4731-5p, circEHD2, and ABCF2. MTT assay was used to analyze cell viability, while apoptosis was studied using flow cytometry. Colony-formation and transwell experiments were used to assess migration and invasion. The ATP Binding Cassette Subfamily F Member 2 (ABCF2) expression was analyzed through western blot. The results showed increased circEHD2 in SU-resistant RCC tissues and cell lines and implicated in RCC histological grade and SU resistance. Knock-down of circEHD2 down-regulated the resistance of RCC to SU in vitro and vivo; circEHD2 bound to miR-4731-5p to mediate ABCF2 in RCC; ABCF2 rescued the inhibitory effect of circEHD2 knock-down on SU resistance of RCC. In conclusion, circEHD2 enhances RCC resistance to SU via acting as a miR-4731-5p sponge to mediate ABCF2. MiR-4731-5p can target circEHD2 and ABCF2, thus providing a novel and effective therapeutic against renal cell carcinoma.

The Imbalance Expression of DLX3 May Perform Critical Function in the Occurrence and Progression of Preeclampsia.

BACKGROUND: The present research focuses on preeclampsia (PE), a clinically relevant pregnancy disease. To date, the majority of research on PE was centered on placental insufficiency. However, the genes that regulate these processes, and the exact molecular mechanisms modulating these processes, are still unclear. METHODS: We obtained placentae from a clinically well-specified group of patients with preeclampsia and gestationally matched control pregnancies in order to evaluate the expression of homeobox gene DLX3 by immunohistochemical staining, real-time PCR, and Western immunoblotting and determine the function of DLX3 utilizing lentivirus transfection in HTR-8/SVneo cells. RESULTS: In the present study, we detected DLX3 expression in a clinically well defined cohort of preeclampsia-affected and gestation-matched control pregnancies. As opposed to the controls, DLX3 was overexpressed in preeclampsia-affected placentae. Moreover, we found that the in vitro cell growth and invasive ability of HTR8/SVneo cells was enhanced by the exogenous overexpression of DLX3 (P < 0.05). It can be seen that DLX3 influences the cell cycle of HTR-8/SVneo cells in vitro. CONCLUSIONS: DLX3 has been shown to be strongly related to normal placental growth as well as the pathophysiology of preeclampsia. The imbalanced expression of DLX3 may perform an integral function in the occurrence and progression of preeclampsia.

Personalized discovery of disrupted pathways and significant genes in preeclampsia based on accumulated normal tissue data.

PURPOSE: This study was designed to identify disrupted pathways in an individual with preeclampsia (PE) using accumulated normal sample data based on individualized pathway aberrance score (iPAS) method. MATERIALS AND METHODS: Pathway data were obtained from the Reactome database. Next, the average Z algorithm was utilized to compute the iPAS. The disrupted pathways in a PE sample were identified by means of t test according to the pathway statistics values of normal and PE samples. In addition, we screened the differential expressed genes (DEGs) using SAMR package and constructed the differential co-expression network comprising DEGs. Subsequently, topological analysis for the co-expression network was conducted to identify hub genes. RESULTS: Under the threshold of false discovery rate <0.05, 69 disrupted pathways were selected. Among them, formation of tubulin-folding intermediates by containing t-complex polypeptide 1 (CCT)/TCP1 ring complex (TriC) was the most remarkable pathway. Degree analysis for co-expression network of DEGs suggested that there were several hub-disrupted pathway-related genes, for instance, TCP1 and TUBA1A. More importantly, these two hub genes were enriched in the most significant pathway of formation of tubulin-folding intermediates by CCT/TriC. CONCLUSION: The iPAS method is suitable for identifying disrupted pathways in PE. Pathway of formation of tubulin folding intermediates by CCT/TriC might play important roles in PE.

[Analysis of genomic copy number variations in fetuses with conotruncal defects using single nucleotide polymorphism array].

OBJECTIVE: To assess the value of single nucleotide polymorphism array (SNP array) for the study of fetuses with conotruncal defects (CTD) detected by echocardiography. METHODS: SNP array was carried out on 75 fetuses with sonographically detected CTD but a normal karyotype. The results were analyzed with ChAS software. RESULTS: Pathogenic CNVs were detected in 7 (9.3%) of all cases. Variant of uncertain significance (VOUS) was detected in 2 (2.7%) cases. Benign CNVs were detected in 19 (25.3%) cases. CONCLUSION: SNP array is an effective method for delineating the etiology of fetuses with CTD, particularly for those with a normal karyotype.