Upregulation of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in non-functioning pituitary adenoma

Long non-coding RNAs (lncRNAs) have been shown to be dysregulated in a variety of malignant and non-malignant lesions including non-functioning pituitary adenomas (NFPAs). In the current experimental study, we have selected six lncRNAs, namely MAPKAPK5-AS1, NUTM2B-AS1, ST7-AS1, LIFR-AS1, PXN-AS1 and URB1-AS1 to assess their expression in a cohort of Iranian patients with NFPA. MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 were shown to be over-expressed in NFPA tissues compared with control samples (Expression ratios (95% CI) = 10 (3.94–25.36), 11.22 (4.3–28.8) and 9.33 (4.12–21.12); p values < 0.0001, respectively). The depicted ROC curves showed the AUC values of 0.73, 0.80 and 0.73 for MAPKAPK5-AS1, PXN-AS1 and URB1-AS1, respectively. Relative expression level of PXN-AS1 was associated with tumour subtype (p value = 0.49). Besides, relative expression levels of MAPKAPK5-AS1 and LIFR-AS1 were associated with gender of patients (p values = 0.043 and 0.01, respectively). Cumulatively, the current study indicates the possible role of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in the pathogenesis of NFPAs.     

Soil organic nitrogen: an overlooked but potentially significant contribution to crop nutrition

Plant and Soil - For more than a century, crop N nutrition research has primarily focused on inorganic N (IN) dynamics, building the traditional model that agricultural plants predominantly take up...     

Persian shallot, <Emphasis Type="Italic">Allium hirtifolium</Emphasis> Boiss,induced apoptosis in human hepatocellular carcinoma cells

This study investigated the potential of Persian shallot extract as an anticancer agent in HepG2 tumor cell line, an in vitro human hepatoma cancer model system. The inhibitory effect of Persian shallot on the growth of HepG2 cells was measured by MTT assay. To explore the underlying mechanism of cell growth inhibition of Persian shallot, the activity of Persian shallot in inducing apoptosis was investigated through the detection of annexin V signal by flow cytometry and expression of some apoptosis related genes such p21, p53, puma, caspase-8 family-Bcl-2 proteins like bid, bim, bcl-2 and bax were measured by real-time PCR in HepG2 cells. Persian shallot extract inhibited the growth of HepG2 cells in a dose-dependent manner. The IC₅₀ value (inhibiting cell growth by 50%) was 149 μg/ml. The results of real-time PCR revealed a significant up-regulation of bid, bim, caspase-8, puma, p53, p21 and bax genes and a significant downregulation of bcl-2 gene in HepG2 cells treated with Persian shallot extract significantly. Therefore, this is the first report on an increased expression of bid, bim, caspase-8, puma, p53, p21 and bax genes and down regulation of bcl-2 gene indicating that the Persian shallot extract possibly induced the process of cell death through the intrinsic and extrinsic apoptosis pathways and triggers the programmed cell death in HepG2 tumor cell lines by modulating the expression of pro-/anti-apoptotic genes. Furthermore, we showed that Persian shallot extract increased annexin V signal and expression, resulting in apoptotic cell death of HepG2 cells after 24 h treatment. Therefore, according to the results of this study, the Persian shallot extract could be considered as a potential candidate for production of drug for the prevention or treatment of human hepatoma.     

Expression analysis of selected miR-206 targets from the transforming growth factor-β signaling pathway in breast cancer

Breast cancer as a molecularly heterogeneous malignancy is associated with dysregulation of several signaling pathways, including transforming growth factor-β (TGF-β) signaling. On the other hand, several recent studies have demonstrated the role of microRNAs (miRNAs) in breast cancer pathogenesis. In the current study, we performed a computerized search to find miR-206 target genes that are functionally linked to the TGF-β signaling pathway. We selected LEF1, Smad2, and Snail2 genes to assess their expression in 65 breast cancer samples and their adjacent noncancerous tissues (ANCTs) in correlation with expression levels of miR-206 as well as clinicopathological characteristics of patients. miR-206 was significantly downregulated in (Estrogen receptor) ER-positive breast cancer samples compared with their corresponding ANCTs. Association analysis between expression levels of genes and demographic features of patients showed significant association between expressions of SMAD2 and LEF1 genes and body mass index ( P values of 0.03 and 0.02, respectively). miR-206 low-expression levels were associated with TNM stage, mitotic rate, and lymph node involvement ( P values of 0.02, 0.01, and 0.01 respectively). In addition, SMAD2 high-expression levels were associated with HER2 status ( P = 0.02). Consequently, our data highlight the role of TGF-β signaling dysregulation in the pathogenesis of breast cancer and warrant further evaluation of miRNAs and messenger RNA coding genes in this pathway to facilitate detection of cancer biomarkers and therapeutic targets.     

Highly upregulated in liver cancer (HULC): An update on its role in carcinogenesis

Highly upregulated in liver cancer (HULC) was initially recognized during the screening of a hepatocellular carcinoma (HCC)-specific gene library. Further studies demonstrated its aberrant upregulation in several other tumor types. The oncogenic roles of this long noncoding RNA (lncRNA) have been verified through expression studies as well as functional studies. Moreover, the results of knockdown experiments have indicated diminished carcinogenic effects of cancer cell line in nude mice following HULC silencing. More recent studies have shown that expression levels of this lncRNA might be used as diagnostic biomarkers in cancer patients. Moreover, mechanistical studies have revealed associations between HULC and two HCC-related viruses namely hepatitis B and C viruses. Taken together, HULC can be regarded as a therapeutic target not only for HCC but also for a variety of human malignancies. In the current review, we summarized the recent literature about the role of HULC in the carcinogenesis and its potential application in cancer diagnosis and prognosis.     

The Effect of Lactobacillus casei Consumption in Improvement of Obsessive–Compulsive Disorder: an Animal Study

Obsessive–compulsive disorder (OCD) is an important neuropsychiatric disorder worldwide. Common treatments of OCD include serotonergic antidepressants, which can cause potentially serious side effects. We assessed the effects of Lactobacillus casei (L. casei) Shirota consumption in an animal model of OCD. OCD-like symptoms were induced in rats by the chronic injection of the D2/D3 dopamine agonist quinpirole hydrochloride. Rats were classified into five groups of 6 rats. Four groups were injected chronically with quinpirole (0.5 mg/kg, twice weekly for 5 weeks). They were fed with L. casei Shirota (10⁹ CF/g, daily for 4 weeks) (group 1), fluoxetine (10 mg/kg, daily for 4 weeks) (group 2), combination of L. casei Shirota and fluoxetine (group 3), and normal saline (positive control group). The last group did not receive dopamine agonist and was only injected with saline (negative control group). Expression levels of brain-derived neurotrophic factor (Bdnf), solute carrier family 6 member 4 (Slc6a4), and 5-hydroxytryptamine receptor type 2A (Htr2a) were assessed in orbitofrontal cortex tissues of all rats. Behavioral tests showed improvement of OCD signs in rats treated with L. casei Shirota, fluoxetine, and a combination of drugs. Quantitative PCR analysis showed a remarkable decrease in the expression of Bdnf and an increase in the expression of Htr2a in quinpirole-treated rats. After treatment with L. casei Shirota and fluoxetine, the expression level of Bdnf was increased remarkably, whereas Htr2a expression was decreased. The current study showed the effectiveness of L. casei Shirota in the treatment of OCD in a rat model. The beneficial effects of this probiotic are possibly exerted through the modulation of serotonin-related genes expression.

     

Taurine-upregulated gene 1: A functional long noncoding RNA in tumorigenesis

Taurine-upregulated gene 1 (TUG1) is a 7.1 kb long noncoding RNA (lncRNA) first recognized in 2005 as an important element for retinal development in rodents. Subsequently, this lncRNA has been shown to participate in oncogenic processes through alteration in chromatin structure, sponging microRNAs, and affecting the expression of some cancer-related pathways. While most of the studies have revealed an oncogenic role for this lncRNA, some reports have shown downregulation of TUG1 in lung cancer samples compared with noncancerous samples. In triple negative breast cancer samples, the expression of this lncRNA has been decreased. Besides, its expression has been higher in HER2-enriched and basal-like subtypes compared with luminal A. In the current review, we discuss the latest literature about the expression pattern and functional roles of TUG1 in diverse cancer types. In addition, its role in epithelial−mesenchymal transition and activation of Wnt/β-catenin pathway in human malignancies will be explored.