Cancer biotherapy & radiopharmaceuticals最新文献

Background: Circular RNAs (circRNAs) are regarded as important regulators in the tumorigenesis of multiple cancers. However, the characterization of circRNA exocyst complex component 6B (circEXOC6B) in ovarian cancer is barely known. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the enrichment of circEXOC6B, microRNA-376c-3p (miR-376c-3p), and forkhead box O3 (FOXO3). Cell proliferation was examined by Cell Counting Kit-8 (CCK8) assay and colony formation assay. Cell metastasis was measured by transwell assays. Western blot assay was conducted to examine the expression of proliferation and metastasis-related proteins and FOXO3. The chemoresistance of ovarian cancer cells was analyzed by CCK8 assay. Flow cytometry was used to detect cell apoptosis. The activities of caspase3 and caspase9 were analyzed through using colorimetric assay kits. The direct interaction between miR-376c-3p and circEXOC6B or FOXO3 was predicted by StarBase software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Murine xenograft assay was conducted to verify the role of circEXOC6B on the paclitaxel (PTX) resistance of ovarian cancer cells in vivo. Results: The level of circEXOC6B was notably decreased in ovarian cancer tissues. Low level of circEXOC6B was associated with malignant pathological characteristics in ovarian cancer patients. CircEXOC6B suppressed the proliferation and motility and decreased the chemoresistance of ovarian cancer cells to PTX. CircEXOC6B functioned through directly targeting and downregulating miR-376c-3p. FOXO3 was a direct target of miR-376c-3p, and the abundance of FOXO3 was regulated by circEXOC6B/miR-376c-3p axis. CircEXOC6B accelerated the PTX sensitivity of ovarian cancer cells through acting as a decoy of miR-376c-3p to upregulate FOXO3 in vivo. Conclusion: CircEXOC6B suppressed the progression and PTX resistance of ovarian cancer cells through sequestering miR-376c-3p, thus enhancing FOXO3 level.

Purpose: The assessment of HER2 expression has a significant impact on optimizing cancer treatment protocol in patients. The aim of this study was to evaluate the potential usefulness of ^99mTc-HYNIC-(Ser)₃-LTVPWY peptide for detecting HER2 alteration after paclitaxel therapy of ovarian tumor xenografts in nude mice. Materials and Methods: Mice bearing SKOV-3 tumors were treated with paclitaxel and saline. The antitumor efficacy of paclitaxel was compared with the control group in tumor size and histopathological examinations. In biodistribution and imaging studies, the tumor uptakes of radiolabeled peptide were evaluated in mice-bearing ovarian tumors in both groups. The HER2 expressions in transplanted tumors were analyzed by immunohistochemistry (IHC). Results: Tumor size gradually increased in all mice during the treatment, whereas tumors had considerably faster growth in the saline group compared to those in the paclitaxel-treated mice. Paclitaxel could suppress ovarian tumor growth and prevent vascular and cell proliferation in the tumoral mass. Biodistribution and imaging results demonstrated nonsignificant radionuclide accumulations in transplanted tumors in the paclitaxel- and saline-treated groups. IHC staining confirmed the HER2 status that was similar in both groups. Conclusions: The response of HER2 status to paclitaxel in mice bearing HER2-expression tumors was profitably monitored by HER2 targeted ^99mTc-HYNIC-(Ser)₃-LTVPWY peptide that was agreement with IHC. The utilization of this radiolabeled peptide may be a valuable probe in evaluating HER2 status after chemotherapy.

Background: Both microRNA (miR)-205 and GATA Binding Protein 3 (GATA3) were involved in cervical cancer (CC), yet their correlation remained poorly understood. The authors' study aimed to unveil their correlation in CC. Materials and Methods: Clinical cervical tissue samples were collected. Survival rates of CC patients with high or low miR-205 and GATA3 expressions were analyzed using Kaplan-Meier curve. CC cell viability, migration, and tube formation were measured by cell counting kit-8 assay, scratch assay, and tube formation assay, respectively. The potential binding sites between miR-205 and GATA3 were predicted by TargetScan, and confirmed with dual-luciferase reporter assay. Relative expressions of miR-205, GATA3, vascular endothelial growth factor, E-cadherin, N-cadherin, and vimentin were quantified with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. Results: MiR-205 was increased, yet GATA3 was decreased in CC, indicating that they were negatively correlated. Upregulating miR-205 increased miR-205 expression and CC cell viability and promoted migration and tube formation, yet decreased GATA3 expression, while downregulating miR-205 exerted the opposite effects. GATA3 was the target gene of miR-205, and reversed the effect of miR-205 on GATA3 expression and cell viability, migration, and tube formation in CC cells by reversing the effects of miR-205 on migration- and tube formation-related protein expressions. Conclusion: MiR-205 promotes CC cell viability, migration, and tube formation in vitro by targeting GATA3, providing new evidence for the implication of miR-205 in CC and a possible therapeutic method for CC. Clinical Trial Registration number: ZLK-20181103-01.

Purpose: N6-methyladenosine (m6A) methylation was the most abundant internal modification on messenger RNAs in eukaryotes. This study intended to explore the role of m6A methylation in endometrial cancer (EC). Materials and Methods: The m6A-sequencing data "GSE93911" of human EC were downloaded from Gene Expression Omnibus database. Hisat2 software and MACS2 were used to perform the alignment of reads and m6A methylation peak calling, and the peaks were annotated using Chipseeker. Then, differential m6A methylation peaks between normal and tumor samples were analyzed, followed by the functional enrichment analysis of the differentially methylated genes in promoter and 3' untranslated region (UTR) using Clusterprofiler. Based on the 450K methylated chip data, gene expression and clinical data in The Cancer Genome Atlas, the differentially methylated genes were verified, followed by Cox univariate/multivariate regression analysis and survival analysis. Finally, a risk prognosis model was constructed. Results: The m6A peak number was decreased in EC. The distribution of m6A peaks was highly enriched near transcriptional start site, in promoter, UTR, intron and exon, followed by distal intergenic. A total of 581 differentially methylated genes (361 hyper- and 220 hypomethylated genes) were identified in promoter and UTR regions that were enriched in insulin resistance (IR) and extracellular matrix (ECM). A total of 181 genes with significant differential expressions and differential methylation site in EC were selected. Of which, 31 genes were correlated with survival, and an 11-gene risk prognosis model was identified, including GDF7, BNC2, SLC8A1, B4GALNT3, DHCR24, ESRP1, HOXB9, IGSF9, KIAA1324, MSnX1, and PHGDH. Conclusion: The m6A methylation regulated EC progression by targeting the genes related to IR and ECM. A 11-gene risk prognosis model was identified to predict survival of patients with EC.

Background: Cervical cancer (CC) is a common gynecological malignancy with a high risk of recurrence and death. Circular RNAs play a crucial role in the occurrence and development of tumors. This study aimed to investigate the function and mechanism of circ_0000745 in CC. Materials and Methods: The levels of circ_0000745, miR-409-3p, and activating transcription factor 1 (ATF1) were determined by quantitative real-time polymerase chain reaction or Western blot assay. Cell proliferation was assessed by colony formation assay. Cell migration and invasion were evaluated by transwell assay. Glycolysis was analyzed by measuring extracellular acidification rate, glucose uptake, and lactate production. Also, the protein levels of glucose transporter 1 and lactate dehydrogenase A were detected using Western blot. The relationship among circ_0000745, miR-409-3p, and ATF1 were confirmed by dual-luciferase reporter assay. Moreover, xenograft assay was performed to analyze tumor growth in vivo. Results: Circ_0000745 and ATF1 were upregulated, whereas miR-409-3p was downregulated in CC tissues and cells. Knockdown of circ_0000745 repressed proliferation, migration, invasion, and glycolysis of CC cells. Circ_0000745 regulated CC progression by targeting miR-409-3p. Circ_0000745 modulated ATF1 expression through sponging miR-409-3p. MiR-409-3p hindered CC progression by targeting ATF1. Furthermore, depletion of circ_0000745 impeded tumor growth in vivo. Conclusion: Circ_0000745 promoted the progression of CC through modulating miR-409-3p/ATF1 axis, indicating a promising biomarker for CC therapy.