Expression of oncolong noncoding RNA taurine-upregulated gene-1 in colon cancer: A clinical study supported by in silico analysis.

Context: Recent studies confirmed that dysregulation of long noncoding RNAs (lncRNAs) is a potential contributor to the development and progression of colon cancer. However, the prognostic value of these RNA molecules remains controversial. Aims: This study aimed to investigate the expression of taurine-upregulated gene-1 (TUG1) lncRNA in colon cancer and its clinical implications. Subjects and Methods: A retrospective study on 47 formalin-fixed, paraffin-embedded samples of surgically resected primary colon cancer specimens was done. Total RNA purified from the colon cancer samples and noncancer adjacent tissue sections was quantified by real-time reverse transcription-polymerase chain reaction (qRT-PCR) to assess TUG1 relative expression levels normalized to GAPDH endogenous control. Also, in silico data analysis was applied. Statistical Analysis Used: The relative expression levels were calculated using the LIVAK method. The survival rates were assessed using the Kaplan-Meier curves and the Cox proportional model. P < 0.05 was considered statistically significant. Results: TUG1expression in the colon cancer specimens was significantly overexpressed (median = 21.50, interquartile range [IQR]: 7.0-209.2; P = 0.001) relative to the noncancerous tissues. In silico analysis confirmed TUG1 upregulation in colon carcinoma (median = 13.92, IQR: 13.5-1432). There were no significant associations between TUG1 expression and clinicopathological characteristics, such as the site, grade, stage, histopathological type, or the rates of lymphovascular invasion and relapse. Similarly, Kaplan-Meir and Cox multivariate regression analyses showed that TUG1 expression could not predict the overall survival and progression-free survival in colon cancer patients of our population. Conclusions: This study confirms the overexpression of TUG1 lncRNA in colon cancer tissues. Larger sample size is warranted to further elucidate the specific role of TUG1 in colon cancer.

MicroRNA-target cross-talks: Key players in glioblastoma multiforme.

The role of microRNAs in brain cancer is still naive. Some act as oncogene and others as tumor suppressors. Discovery of efficient biomarkers is mandatory to debate that aggressive disease. Bioinformatically selected microRNAs and their targets were investigated to evaluate their putative signature as diagnostic and prognostic biomarkers in primary glioblastoma multiforme. Expression of a panel of seven microRNAs (hsa-miR-34a, hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, hsa-miR-326, and hsa-miR-375) and seven target genes ( E2F3, PI3KCA, TOM34, WNT5A, PDCD4, DFFA, and EGFR) in 43 glioblastoma multiforme specimens were profiled compared to non-cancer tissues via quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry staining for three proteins (VEGFA, BAX, and BCL2) was performed. Gene enrichment analysis identified the biological regulatory functions of the gene panel in glioma pathway. MGMT ( O-6-methylguanine-DNA methyltransferase) promoter methylation was analyzed for molecular subtyping of tumor specimens. Our data demonstrated a significant upregulation of five microRNAs (hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, and hsa-miR-375), three genes ( E2F3, PI3KCA, and Wnt5a), two proteins (VEGFA and BCL2), and downregulation of hsa-miR-34a and three other genes ( DFFA, PDCD4, and EGFR) in brain cancer tissues. Receiver operating characteristic analysis revealed that miR-34a (area under the curve = 0.927) and miR-17 (area under the curve = 0.900) had the highest diagnostic performance, followed by miR-221 (area under the curve = 0.845), miR-21 (area under the curve = 0.836), WNT5A (area under the curve = 0.809), PDCD4 (area under the curve = 0.809), and PI3KCA (area under the curve = 0.800). MGMT promoter methylation status was associated with high miR-221 levels. Moreover, patients with VEGFA overexpression and downregulation of TOM34 and BAX had poor overall survival. Nevertheless, miR-17, miR-221, and miR-326 downregulation were significantly associated with high recurrence rate. Multivariate analysis by hierarchical clustering classified patients into four distinct groups based on gene panel signature. In conclusion, the explored microRNA-target dysregulation could pave the road toward developing potential therapeutic strategies for glioblastoma multiforme. Future translational and functional studies are highly recommended to better understand the complex bio-molecular signature of this difficult-to-treat tumor.