Inhibition of breast cancer cell growth and migration through siRNA-mediated modulation of circ_0009910/miR-145-5p/MUC1 axis.

Circular RNAs (circRNAs) characterize a novel kind of regulatory RNAs distinguished by great evolutionary conservation and constancy. Although their exact role in malignancies is not fully understood, they mainly work through specific axes. Circular RNA/miRNA/mRNA axes affect the pathogenesis of human cancers including breast cancer. We assessed the expression and function of circ_0009910/miR-145-5p/MUC1 axis in Breast Cancer tissues and MCF-7 cells. Expression levels of circ_0009910 and MUC1 were notably increased in breast cancer tissues compared with control tissues, parallel with the down-regulation of miR-145-5p. Clinicopathological analysis indicated that up-regulation of circ_0009910 in breast tumors is related to invasion of the tumor to lymph node (P value = 0.011). Also, the downregulation of miR-145-5p was significantly correlated with tumor invasion to lymph nodes (P value = 0.04) and HER2-negative tumors (P value = 0.037). Finally, overexpression of MUC1 was correlated with age under 45 years (P value = 0.002). More importantly, circ_0009910-siRNA decreased the proliferation and migration ability of breast cancer cells, enhanced expression of miR-145-5p, and decreased levels of MUC1. Taken together, the circ_0009910/miR-145-5p/MUC1 axis has been demonstrated to affect the pathogenesis of breast cancer and might provide a target for breast cancer treatment.

Long non-coding RNA (lncRNA) DSCAM-AS1 is upregulated in breast cancer.

BACKGROUND: Accumulating evidence highlights that long noncoding RNA (lncRNA) DSCAM-AS1 play a key regulatory role in different stages of cancer development and progression. This study aimed to investigate whether the expression of DSCAM-AS1 is deregulated in breast cancer. MATERIALS AND METHODS: The relative expression of DSCAM-AS1 was measured in fifty breast cancerous and matched adjacent non-neoplastic tissue samples using quantitative real-time polymerase chain reaction (qPCR) technique. The association between DSCAM-AS1 expression and patients' clinicopathological features was evaluated. Sensitivity and specificity of the DSCAM-AS1 expression for diagnosing breast cancer was obtained by the receiver operating characteristic (ROC) curve analysis. RESULTS: Our results showed that the expression of DSCAM-AS1 was significantly up-regulated in breast cancerous tissues compared with the matched adjacent non-neoplastic tissues (P < 0.05). Furthermore, we observed a significant association between the DSCAM-AS1 expression and lymph node metastasis (P = 0.011) but no other clinicopathological characteristics (P > 0.05). ROC curve analysis resulted in an area under the curve (AUC) of 0.67 and showed that the DSCAM-AS1 expression level may discriminate cancerous and non-cancerous tissues with 68% sensitivity and 76% specificity. CONCLUSION: This study provides further evidence that the expression of DSCAM-AS1 is deregulated in breast cancer and highlights its potential in breast cancer development.

Association between miR-146a C > G, miR-149 T > C, miR-196a2 T > C, and miR-499 A > G polymorphisms and susceptibility to idiopathic recurrent pregnancy loss.

BACKGROUND: A growing body of evidence suggests that microRNAs play fundamental regulatory roles in embryo implantation and maintenance of pregnancy. The aim of this study was to investigate the possible association between miR-146a C > G, miR-149 T > C, miR-196a2 T > C, and miR-499 A > G polymorphisms and genetic susceptibility to recurrent pregnancy loss (RPL). MATERIAL AND METHODS: One hundred and twenty women with a history of two or more unexplained consecutive miscarriages and 90 ethnically matched healthy women with a history of at least two successful pregnancy outcomes and without a history of miscarriage were enrolled in a case-control study. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Our findings showed that the prevalence of miR-149 T > C polymorphism in RPL patients was significantly higher than those in healthy controls (p < 0.05). We also found that the presence of miR-149 C and miR-499 G alleles was significantly associated with susceptibility to RPL (p < 0.05). The miR-146a CC/miR-499 GG, miR-149 TC/miR-499 AG, and miR-196a2 TT/miR-499 GG combined genotypes were associated with the high risk of RPL (p < 0.05). CONCLUSION: This study suggests that miR-149 T > C polymorphism and the presence of miR-149 C, and miR-499 G alleles are a genetic determinant for the risk of idiopathic RPL.

Isolation and characterization of human amniotic fluid and SH-SY5Y/ BE(2)-M17 cell derived exosomes.

The application of stem cells as a therapy for degenerative disease holds great promise. Substantial evidence suggests that stem cell derived exosomes are a novel cell-free therapy for the corresponding cells. Exosomes are less complex as compared to their parental cells, due to the fewer number of membrane proteins. In addition, the smaller size and lower risk of immunogenicity makes exosomes potentially safe therapeutic nano-carriers. A large number of ongoing research studies are focused on characterizing exosomes that were derived from different sources, for their potential use in various therapeutic applications. In the present study, we focused on characterizing human amniotic fluid stem cell derived exosomes for future therapeutic applications, such as paracrine therapy/nano carrier. In addition, we characterized exosomes derived from SH-SY5Y and BE(2)-M17 cells, which are a known neuronal model, for further characteristic analyses of neuronal differentiation and neurobiology. Finally, we compared various exosome isolation techniques and procedures and evaluated exosome yield.

Simultaneous downregulation of miR-21 and miR-155 through oleuropein for breast cancer prevention and therapy.

Breast cancer (BC) is the leading cause of cancer mortality in women worldwide. It recently was proven that miRNAs play a critical role in BC development. The use of natural agents for control of cancer by modulating miRNAs is promising. Oleuropein is a natural polyphenolic agent with anti-neoplastic properties and is well tolerated by humans. This study was undertaken to determine the therapeutic effects of oleuropein through modulation of master oncomiRs (miR-21 and miR-155) in BC cells. The present study provides the first link between miRNA and oleuropein as a mechanism in BC. MCF-7 cells were tested with and without oleuropein and the cell viability, apoptosis, and migration were examined. The effect of oleuropein on miR-21 and miR-155 expression was assessed through qRT-PCR. It was found that oleuropein induced apoptosis and retarded cell migration and invasion in a dose-dependent manner in the human MCF7 BC cell line. It was observed that oleuropein significantly decreased expression of both miR-21 and miR-155 over time in a dose-dependent manner. These results demonstrate that oleuropein is a potential therapeutic and preventive agent for BC. Oleuropein exhibits an anti-cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs.