CircPDSS1 promotes the proliferation, invasion, migration, and EMT of breast cancer cell via regulating miR-320c/CKAP5 axis.

BACKGROUND: Breast cancer (BC) poses serious threats to women's health. A large number of reports have proved that circular RNAs (circRNAs) exert vital functions in human cancers, including BC. METHODS: The function of circPDSS1 in BC cells was tested by CCK-8, colony formation, TUNEL, transwell-invasion, wound healing, and IF assays. RNA pull down, luciferase reporter and RIP assays were employed to verify the relationship among circPDSS1, miR-320c and CKAP5. RESULTS: CircPDSS1 was upregulated in BC cells, and circPDSS1 knockdown repressed BC cell malignant behaviors. Further, circPDSS1 was found to bind to miR-320c in BC cells, and miR-320c overexpression suppressed malignant processes of BC cells. MiR-320c could also bind to CKAP5. Moreover, miR-320c inhibition increased the level of CKAP5, but circPDSS1 downregulation decreased the level of CKAP5. Finally, rescue experiments indicated that CKAP5 knockdown countervailed the promoting effect of miR-320c inhibition on the malignant behaviors of circPDSS1-depleted BC cells. CONCLUSIONS: CircPDSS1 promotes proliferation, invasion, migration as well as EMT of BC cells by modulating miR-320c/CKAP5 axis. Our finding may be useful for researchers to find new potential therapeutic or diagnostic targets for BC.

Long noncoding RNA SOX21-AS1 regulates the progression of triple-negative breast cancer through regulation of miR-520a-5p/ORMDL3 axis.

Recently, long noncoding RNAs (lncRNAs) have been reported as a new kind of controllers about cancer processes in biology. In spite of the dysregulation of lncRNAs in various kinds of cancers, only a little of the information was effective on the expression configuration and inner effects of lncRNAs in triple-negative breast cancer (TNBC). This study valued the expression of lncRNA SOX21-AS1 and the biological role it played in TNBC. In our research, SOX21-AS1 had a high expression in TNBC cell lines. The functional experiments showed that knockdown of SOX21-AS1 obviously restrained cell proliferation, migration, invasion, and epithelial-mesenchymal transition process and promoted cell apoptosis. Mechanistically, SOX21-AS1 was found to bind with miR-520a-5p. Besides, ORMDL3 was identified as a downstream target of miR-520a-5p, and the suppressed ORMDL3 expression induced by silenced SOX21-AS1 could be restored by miR-520a-5p inhibition. Further, data from rescue assays revealed that SOX21-AS1 could regulate the malignancy of TNBC via miR-520a-5p/ORMDL3 axis. All in all, we identified that SOX21-AS1 regulated the cellular process of TNBC cells via antagonizing miR-520a-5p availability to upregulate ORMDL3 expression.

MicroRNA-181d-5p-Containing Exosomes Derived from CAFs Promote EMT by Regulating CDX2/HOXA5 in Breast Cancer.

Recently, novel mechanisms underlying the pro-tumorigenic effects of cancer-associated fibroblasts (CAFs) have been identified in several cancers, including breast cancer. CAFs can secrete exosomes that are loaded with proteins, lipids, and RNAs to affect tumor microenvironment. Herein, we identify CAF-derived exosomes that can transfer miR-181d-5p to enhance the aggressiveness of breast cancer. Cancerous tissues and matched paracancerous tissues were surgically resected from 122 patients with breast cancer. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were employed to identify interaction between homeobox A5 (HOXA5) and caudal-related homeobox 2 (CDX2), as well as between CDX2 and miR-181d-5p, respectively. Human breast cancer Michigan Cancer Foundation-7 (MCF-7) cells were cocultured with CAF-derived exosomes. 5-Ethynyl-2'-deoxyuridine (EdU) assay, TUNEL staining, Transwell invasion assays, and scratch tests were carried out to evaluate MCF-7 cell functions. Nude mice bearing xenografted MCF-7 cells were injected with CAF-derived exosomes, and the tumor formation was evaluated. HOXA5 expressed at a poor level in breast cancer tissues, and its overexpression retarded MCF-7 cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) and facilitated its apoptosis in vitro. miR-181d-5p targets CDX2, a transcription factor binding to HOXA5 promoter. Coculture of CAFs and MCF-7 cells showed that CAFs prolonged proliferation and antagonized apoptosis of MCF-7 cells via release of exosomes. Coculture of MCF-7 cells and exosomes derived from CAFs identified miR-181d-5p as a mediator of the exosomal effects on MCF-7 cells, in part, via downregulation of CDX2 and HOXA5. CAF-derived exosomes containing miR-181d-5p promoted the tumor growth of nude mice bearing xenografted MCF-7 cells. In conclusion, exosomal miR-181d-5p plays a key role in CAF-mediated effects on tumor environment in breast cancer, likely via CDX2 and HOXA5.

Down-regulated expression of LINC00518 prevents epithelial cell growth and metastasis in breast cancer through the inhibition of CDX2 methylation and the Wnt signaling pathway.

Breast cancer (BC)-related mortality is associated with the potential metastatic properties of the primary breast tumors. The following study was conducted with the main focus on the effect of LINC00518 on the growth and metastasis of BC epithelial cells via the Wnt signaling pathway through regulation of the methylation of CDX2 gene. Initially, differentially expressed long intergenic non-protein coding RNAs (lincRNAs) related to BC were screened out in the Cancer Genome Atlas (TCGA) database, after which we detected the LINC00518 expression and localization in BC tissues and cells. Then the CDX2 positive expression and methylation level were identified. The targeting relationship of LINC00518 and CDX2, and binding methyltransferase in the promoter region were examined. BC epithelial cell proliferation, colony formation ability, invasion, migration and apoptosis were further evaluated. The lincRNA expression data related to BC downloaded from the TCGA database revealed that there was a high expression of LINC00518 in BC, and a negative correlation between LINC00518 and CDX2. In addition, LINC00518 promotes CDX2 methylation by recruiting DNA methyltransferase through activating the Wnt signaling pathway. The down-regulation of LINC00518 inhibited proliferation, invasion, migration, and EMT of BC epithelial cells while enhancing apoptosis. The inhibitory effects of LINC00518 down-regulation was reversed by CDX2 down-regulation. In conclusion, our findings revealed that down-regulation of LINC00518 might have the ability to suppress BC progression by up-regulating CDX2 expression through the reduction of methylation and blockade of the Wnt signaling pathway, resulting in the inhibition of proliferation and promotion of apoptosis of BC epithelial cells.

Electrochemical studies of (-)-epigallocatechin gallate and its interaction with DNA.

In this paper, an electrochemical investigation of (-)-epigallocatechin gallate (EGCG) and its interaction with DNA is presented. Via an electrochemical approach assisted by ultraviolet-visible (UV-Vis) spectroscopy, we propose that EGCG can intercalate into DNA strands forming a nonelectroactive complex, which results in the decrease of the anodic peak current of EGCG. Meanwhile, an electrochemical study with the DNA-Cu(II)-EGCG system shows that damage to DNA can be recognized electrochemically via the increase in the anodic peak current resulting from the oxidation of guanine and adenine bases. The damage can also be recognized spectrophotometrically via an increase in the 260 nm absorption band. In addition, it was found that EGCG is able to discriminate dsDNA from ssDNA, making a potential electrochemical indicator for the detection of DNA hybridization events. A rapid and convenient method of detecting EGCG was also developed in this work.