Long noncoding RNAs (lncRNAs) have emerged as new regulators of stem cell pluripotency and tumorigenesis. The SOX2 gene, a master regulator of pluripotency, is embedded within the third intron of a lncRNA known as SOX2 overlapping transcript (SOX2OT). SOX2OT has been suspected to participate in regulation of SOX2 expression and/or other related processes; nevertheless, its potential involvement in tumor initiation and/or progression is unclear. Here, we have evaluated a possible correlation between expression patterns of SOX2OT and those of master regulators of pluripotency, SOX2 and OCT4, in esophageal squamous cell carcinoma (ESCC) tissue samples. We have also examined its potential function in the human embryonic carcinoma stem cell line, NTERA2 (NT2), which highly expresses SOX2OT, SOX2, and OCT4. Our data revealed a significant coupregulation of SOX2OT along with SOX2 and OCT4 in tumor samples, compared to the non-tumor tissues obtained from the margin of same tumors. We also identified two novel splice variants of SOX2OT (SOX2OT-S1 and SOX2OT-S2) which coupregulated with SOX2 and OCT4 in ESCCs. Suppressing SOX2OT variants caused a profound alteration in cell cycle distribution, including a 5.9 and 6.9 time increase in sub-G1 phase of cell cycle for SOX2OT-S1 and SOX2OT-S2, respectively. The expression of all variants was significantly diminished, upon the induction of neural differentiation in NT2 cells, suggesting their potential functional links to the undifferentiated state of the cells. Our data suggest a part for SOX2OT spliced variants in tumor initiation and/or progression as well as regulating pluripotent state of stem cells. STEM CELLS 2014;32:126-134

We observed significant up-regulation of miR-196a in esophageal squamous cell carcinoma (ESCC) as compared with their adjacent normal tissue (p = .002). Receiver operating characteristics curve analysis confirmed the suitability of miR-196a as a potential tumor marker for diagnosis of ESCC. Furthermore, analysis of miR-196a levels in saliva samples determined an average of 27-fold up-regulations in ESCC patients compared with healthy group. Our results suggest that salivary miR-196a may be a suitable noninvasive biomarker for diagnosis of ESCC. In addition, molecular pathway enrichment analysis of microRNA (miR)-196a determined focal adhesion, spliceosome and p53 signaling pathways as the most relevant pathways with miR-196a targetome.

Background: Breast cancer is the most prevalent cancer and the fifth cause of cancer death in Iranian women. Early detection and treatment are important for appropriate management of this disease. Mammography and ultrasonography are used for screening and evaluation of symptomatic cases and the main diagnostic test for breast cancer is pathological. In this study we evaluated mammography and ultrasonography as diagnostic tools. Methods: In this cross-sectional study 384 mammography and ultrasonography reports for 255 women were assessed, divided into benign and malignant groups. Suspected cases were referred for pathology evaluation. The radiologic and pathologic reports were compared and also comparison was performed based on age groups (more and less than 50 years old), history of breastfeeding and gravidity. Statistical analysis was performed by SPSS. Results: The mean ages of malignant and benign cases were 49±11.6 and 43±11.2 years, respectively. Sensitivity and specificity for mammography were 73% and 45%, respectively. Sensitivity and specificity for ultrasonography were 69% and 49%, respectively. There were statistical differences between specificity of mammography in patients based on factors such as history of gravidity, breastfeeding and sensitivity in patients equal or more than 50 years old and less. Conclusion: Factors affecting different results in mammography and ultrasonography reports were classified into three groups, consisting of skill, experience and training of medical staff, and setting of instruments. It is recommended that health managers in developing countries pay attention the quality of setting and man power more than current status. Policy-makers and managers must establish guidelines regarding breast imaging in Iran.

BackgroundHelicobacter pylori is a major human pathogenic bacterium in gastric mucosa. Although the association between gastric cancer and H. pylori has been well-established, the molecular mechanisms underlying H. pylori-induced carcinogenesis are still under investigation. MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression at the posttranscriptional level. Recently, studies have revealed that miRNAs are involved in immune response and host cell response to bacteria. Also, microRNA-375 (miR-375) is a key regulator of epithelial properties that are necessary for securing epithelium-immune system cross-talk. It has been recently reported that miR-375 acts as an inhibitor of H. pylori-induced gastric carcinogenesis. There are few reports on miRNA-mediated targeting long noncoding RNAs (lncRNAs).ObjectivesThis study aimed to examine the possible effect of miR-375 as an inhibitor of H. pylori-induced carcinogenesis on the expression of lncRNA SOX2 overlapping transcript (SOX2OT) and SOX2, a master regulator of pluripotency of cancer stem cells.Materials and MethodsIn a model cell line, NT-2 was transfected with the constructed expression vector pEGFP-C1 contained miR-375. The RNA isolations and cDNA synthesis were performed after 48 hours of transformation. Expression of miR-375 and SOX2OT and SOX2 were quantified using real-time polymerase chain reaction and compared with control cells transfected with pEGFP-C1-Mock clone. Cell cycle modification was also compared after transfections using the flow cytometry analysis.ResultsFollowing ectopic expression of miR-375, SOX2OT and SOX2 expression analysis revealed a significant decrease in their expression level (P < 0.05) in NT-2 cells compared to the control. Cell cycle analysis following ectopic expression of miR-375 in the NT-2 cells using propidium iodine staining revealed significant extension in sub-G1 cell cycle.ConclusionsThis is the first report to show down-regulation of SOX2OT and SOX2 following induced expression of miR-375. This finding may suggest expression regulation potential between different classes of ncRNAs, for example between miR-375 and SOX2OT. This data not only extends our understanding of possible ncRNA interactions in cancers but also may open novel investigation lines towards elucidation of molecular mechanisms controlling H. pylori inflammation and carcinogenesis.