Long noncoding RNA PVT1: A highly dysregulated gene in malignancy

Recent studies have verified the contribution of several long noncoding RNAs (lncRNAs) in the carcinogenesis. Among the highly acknowledged lncRNAs is the human homolog of the plasmacytoma variant translocation gene, which is called PVT1. PVT1 resides near Myc oncogene and regulates the oncogenic process through modulation of several signaling pathways, such as TGF-β, Wnt/ β-catenin, PI3K/AKT, and mTOR pathways. This lncRNA has a circular form as well. Expression analyses and functional studies have appraised the oncogenic roles of PVT1 and circPVT1. Experiments in several cancer cell lines have shown that PVT1 silencing suppresses cancer cell proliferation, whereas its overexpression has the opposite effect. Its silencing has led to the accumulation of cells in the G0/G1 phase and diminished the number of cells in the S phase. Moreover, genome-wide association studies have signified the role of single nucleotide polymorphisms of this lncRNA in conferring risk of lymphoma in different populations. In the current study, we have summarized recent data about the role of PVT1 and circPVT1 in the carcinogenesis process.     

Blood and tissue levels of lncRNAs in periodontitis

Periodontitis is a complex disorder that affects a large number of human beings from different ethnic groups. This condition has been associated with dysregulation of a number of genes, among them are long noncoding RNAs (lncRNAs). In the current study, we assessed the expression of four lncRNAs (BDNF-AS, MIAT, MIR137HG, and PNKY) as well as BDNF in the peripheral blood and gingival tissues obtained from patients with periodontitis and healthy subjects. The expression of BDNF was significantly lower in blood samples of male patients with periodontitis compared with male controls (posterior β of RE = −4.754, p = .048). However, there was no significant difference in the expression of BDNF in tissue samples from the cases and controls. The expression of BDNF-AS was significantly lower in the tissue samples of patients compared with control tissue samples (posterior β of RE = −2.151, p = .019). Such an expression difference was detected between male subgroups as well (posterior β of RE = −3.679, p = .009). However, expression of this lncRNA was not different in blood samples obtained from patients compared with healthy subjects. The expression of PNKY was significantly higher in tissue samples obtained from female patients compared with sex-matched controls (posterior β of RE = 6.23, p = .037). Blood levels of this lncRNA were not different between cases and controls. There was no significant difference either in the tissue expression or in blood expression of MIR137HG or MIAT between cases and controls. The current study indicates the putative role of BDNF, BDNF-AS, and PNKY in the pathophysiology of periodontitis and potentiates these genes as candidates for functional studies.     

Expression profile of lncRNAs and miRNAs in esophageal cancer: Implications in diagnosis,prognosis, and therapeutic response

Esophageal cancer is the seventh most common cancer worldwide. Although a number of environmental and lifestyle-related risk factors have been identified for this kind of cancer, the exact molecular mechanisms of tumor evolution have not been clarified yet. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) as important regulators of gene expression and chromatin configuration have essential roles in the pathogenesis of esophageal cancer. They have been shown to alter the function of cancer-related signaling pathways such as phosphoinositide 3-kinase/protein kinase B and Wnt pathway, thus they might modulate the response of patients to pathway-targeted therapies. Moreover, a number of lncRNAs, such as AFAP1-AS1, UCA1, HOTAIR, LOC285194, and TUSC7, are involved in conferring chemoresistant/radioresistant in esophageal cancer cells. A complex network of interaction exists between lncRNAs and miRNAs in the context of esophageal cancer. Finally, various panels of lncRNAs and miRNAs have been introduced that can predict the survival of esophageal cancer patients. In this review article, we summarize the recent findings regarding the role of miRNAs and lncRNAs in the pathogenesis of esophageal cancer with the special focus on their regulatory roles on signaling pathways, their potential as diagnostic/prognostic markers, and their relevance with therapeutic response.     

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.     

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.