Construction of ceRNA network and identification of hub differentially expressed genes associated with breast cancer using reanalysis of microarray dataset: A systems biology approach.

The interaction between long non-coding RNAs (lncRNAs), miRNAs and mRNAs has implications in the pathogenesis of different cancer, including breast cancer. In the current study, we developed an in-silico approach to ascertain the competing endogenous RNA (ceRNA) network in breast cancer. Our approach led to identification of 1816 differentially expressed (DE) mRNAs, including 1039 downregulated DEmRNAs (such as LEP and ADIPOQ) and 777 upregulated DEmRNAs (such as COL11A1 and COL10A1), 19 DElncRNAs, including 15 downregulated DElncRNAs (such as CARMN and COPG2IT1) and 4 upregulated DElncRNAs (such as MALAT1 and NRAV) and 27 DEmiRNAs, including 15 downregulated DEmiRNAs (such as MIR452 and MIR224) and 12 upregulated DEmiRNAs (such as MIR6787 and MIR21). Pathway analysis revealed down-regulation of PPAR, Fatty acid metabolism, Adipocytokine, Vascular smooth muscle contraction and Metabolism of xenobiotics by cytochrome P450, while up-regulation of Pyrimidine metabolism, p53 signaling pathway, Cell cycle, Oocyte meiosis and RNA transport pathways in breast cancer. Finally, we constructed an lncRNA/miRNA/mRNA ceRNA network consisted of 2 lncRNAs, 15 mRNAs, and 4 miRNAs. This network represents an appropriate target for design of anti-cancer modalities and documentation of novel markers for breast cancer.

Assessment of the effects of intrastromal injection of adipose-derived stem cells in keratoconus patients.

AIM: To evaluate the efficacy and safety of intrastromal transplantation of adipose-derived stem cells (ASCs) in keratoconus patients. METHODS: This study was conducted on 8 eyes of 8 patients with moderate to severe keratoconus. In the patients, ophthalmic assessments including visual acuity, refraction, slit lamp examination, fundoscopy, corneal topography, and confocal microscopy were performed. Autologous stem cells were used. The isolated stem cells were injected into the corneal stroma by using femtosecond laser. Surgical procedure was similar to intracorneal ring implantation. All patients were re-assessed 1, 3, and 6mo after surgery. RESULTS: The baseline mean visual acuity was 0.48±0.18 and improved to 0.66±0.17 after surgery and final acuity increased by 1.85±0.80 lines (P=0.001). The mean spherical refraction of patients improved 0.34±0.35 D (P=0.039), and the mean cylindrical refraction of patients improved 0.84±0.23 D (P=0.016). The mean flat keratometry decreased 0.78±0.71 D (P=0.017), and the mean steep keratometry decreased 0.59±0.68 D (P=0.023). The mean central corneal thickness of patients improved of 6.29±4.47 µm (P=0.03). The mean keratocyte density at the anterior and middle stroma of cornea increased (P<0.05) but remained stable at the posterior stroma after 6mo. All patients had no complications and their corneas remained transparent. CONCLUSION: Intrastromal transplantation of ASCs has positive effects on vision and refractive parameters in most patients with keratoconus. After six months, visual acuity improved moderately, corneal parameters reduced slightly, and stromal keratocytes density increased. This modality is safe, and patients do not have any complications.

Expression of Treg-associated lncRNAs in breast cancer.

Regulatory T cells (Tregs) have important functions in tumor microenvironment, particularly for induction of immune evasion. In order to find the underlying mechanism of dysregulation of Tregs in breast cancer tissues, we designed the current study to appraise expression of five Treg-related long non-coding RNAs (lncRNAs), namely FLICR (FOXP3 Regulating Long Intergenic Non-Coding RNA), NEST (IFNG-AS1), RMRP (RNA Component of Mitochondrial RNA Processing Endoribonuclease), MAFTRR (MAF Transcriptional Regulator RNA) and TH2-LCR (Th2 Cytokine Locus Control Region) in paired breast cancer and nearby noncancerous tissues. Expression levels of RMRP, TH2-LCR, MAFTRR and GATA3-AS1 were significantly higher in breast cancer samples compared with non-tumoral tissues. The calculated AUC values for GATA3-AS1, TH2-LCR, RMRP and MAFTRR were 0.66, 0.63, 0.63 and 0.60, respectively. There were significant positive associations between expression level of RMRP gene in tumor tissues and nuclear grade, tubule formation and tumor sizes. In addition, there was a significant positive association between expression levels of MAFTRR genes in tumor tissues and nuclear grade. Besides, expression levels of FLICR were different among tumors with different levels of HER2/neu receptor. Taken together, Treg-associated lncRNAs might contribute to the pathogenesis of breast cancer.