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.     

LncRNA–CDC6 promotes breast cancer progression and function as ceRNA to target CDC6 by sponging microRNA-215

Rapid proliferation and metastasis of breast cancers resulted in poor prognosis in clinic. Recent studies have proved that long noncoding RNAs (lncRNAs) were involved in tumor progression. In this study, we aimed to determine the roles and mechanisms of lncRNA–cell division cycle 6 (CDC6) in regulating proliferation and metastasis of breast cancer. Clinically, lncRNA–CDC6 was highly expressed in tumor tissues and was positively correlated with clinical stages of breast cancers. Functionally, the ectopic expression of lncRNA–CDC6 promoted proliferation via regulation of G1 phase checkpoint, and further promoting the migration capability. Moreover, lncRNA–CDC6 could function as competitive endogenous RNA (ceRNA) via directly sponging of microRNA-215 (miR-215), which further regulating the expression of CDC6. Taken together, our results proved that lncRNA–CDC6 could function as ceRNA and promote the proliferation and metastasis of breast cancer cells, which provided a novel prognostic marker for breast cancers in clinic.     

ceRNA network construction and comparison of gastric cancer with or without Helicobacter pylori infection

Gastric cancer (GC) is a lethal disease, and among its variety of etiological factors, Helicobacter pylori (H. pylori) infection is the strongest risk factor. However, the genetic and molecular mechanisms underlying H. pylori-related GC need further elucidation. We investigated the competing endogenous RNA (ceRNA) network differences between H. pylori (+) and H. pylori (−) GC. The long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression data from 32 adjacent noncancerous samples and 18 H. pylori (+) and 141 H. pylori (−) stomach adenocarcinoma samples were downloaded from the TCGA database. After construction of lncRNA–miRNA–mRNA ceRNA networks of H. pylori (+) and H. pylori (−) GC, Panther and Kobas databases were used to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, survival analysis was used to discover the key genes. In H. pylori (+) GC, we identified a total of 1,419 lncRNAs, 82 miRNAs, and 2,501 mRNAs with differentially expressed profiles. In H. pylori (−) GC, 2,225 lncRNAs, 130 miRNAs, and 3,146 mRNAs were differentially expressed. Furthermore, three unique pathways (cytokine–cytokine receptor interaction, HIF-1 signaling pathway, and Wnt signaling pathway) were enriched in H. pylori (+) GC. According to the overall survival analysis, three lncRNAs (AP002478.1, LINC00111, and LINC00313) and two mRNAs (MYB and COL1A1) functioned as prognostic biomarkers for patients with H. pylori (+) GC. In conclusion, our study has identified the differences in ceRNA regulatory networks between H. pylori (+) and H. pylori (−) GC and provides a rich candidate reservoir for future studies.     

Long noncoding RNA ATB participates in the development of renal cell carcinoma by downregulating p53 via binding to DNMT1

Long noncoding RNA (lncRNA) exerts an essential role in the pathological processes of many diseases. Our previous study found that lncRNA ATB was highly expressed in renal cell carcinoma (RCC). Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and migration-related assays were conducted to access the regulatory effects of lncRNA ATB on proliferative and migratory capacities of RCC cells. Flow cytometry was carried out to determine cell cycle and apoptosis influenced by lncRNA ATB. The interaction among lncRNA ATB, DNMT1, and p53 was evaluated through RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and western blot analyses. The results showed that lncRNA ATB knockdown in RCC cell line ACHN inhibited proliferative and migratory capacities and promoted apoptosis. Meanwhile, overexpression of lncRNA ATB in RCC cell line A-498 promoted proliferative and migratory capacities but inhibited apoptosis. RIP and ChIP assays confirmed that lncRNA ATB can bind to DNMT1 and stabilize its expression; meanwhile, it can promote the binding of DNMT1 to p53. Overexpression of p53 partially reversed the proliferative and migratory changes caused by lncRNA ATB. To sum up, our study revealed that high expression of lncRNA ATB could accelerate the proliferative and migratory rates of RCC cells and inhibit cell apoptosis through downregulating p53 via binding to DNMT1.