Clinicopathological Significance of Long Non-Coding RNA GHET1 in Human Cancers: A Meta-Analysis.

BACKGROUND: Cancer is considered as the main public health problem and the second leading cause of morbidity and mortality worldwide. Numerous environmental-lifestyle related risk factors account for around one-third of cancer deaths. Recently, the key role of lncRNAs has been widely investigated in a variety of disorders, including cancer. The lncRNA GHET1 has been considered as an essential oncogenic lncRNA in many types of human cancers. Clinical investigations indicated that expression of lncRNA GHET1 is correlated with clinicopathological characteristics in cancer. This metaanalysis investigated the correlation between the lncRNA GHET1 expression and clinicopathological features in different types of cancers. MATERIALS AND METHODS: Comprehensive literature searches in PubMed, Scopus, and Web of Knowledge were conducted up to April 11, 2019. Sixteen studies were included in this meta-analysis. All statistical analyses were conducted using Stata software, version 12.0. RESULTS: The pooled OR and 95%CIs of the sixteen relevant studies showed that over expression of lncRNA GHET1 was associated with tumor-size ≥5 cm (OR= 2.51, 95% CI: 1.89-3.33, p=0.00, I2=38.30%), positive lymph node metastasis (OR= 2.83, 95% CI: 1.78-4.52, p=0.00, I2=45.60%), advanced tumor stage (OR= 3.92, 95% CI: 2.97-5.19, p=0.00, I2=0.00%), positive distant metastasis (OR= 5.74, 95% CI: 2.58-12.77, p=0.00, I2=0.00%), advanced tumor status (OR= 2.97, 95% CI: 1.40- 6.29, p=0.01, I2=34.70%), and positive vascular invasion (OR= 2.69, 95% CI: 1.61-4.50, p=0.00, I2=29.20%). CONCLUSION: Taken together, the current study demonstrated that overexpression of lncRNA GHET1 is significantly associated with clinicopathological features in human cancers. Our results suggested that lncRNA GHET1 can be utilized as a prognostic biomarker in human cancer.

Integration analysis of long non-coding RNA (lncRNA) role in tumorigenesis of colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is one of the most common gastrointestinal cancers globally. Molecular aberrations of tumor suppressors and/or oncogenes are the main contributors to tumorigenesis. However, the exact underlying mechanisms of COAD pathogenesis are clearly not known yet. In this regard, there is an urgent need to indicate promising potential diagnostic and prognostic biomarkers in COAD patients. METHODS: In the current study, level 3 RNA-Seq and miR-Seq data and corresponding clinical data of colon adenocarcinoma (COAD) were retrieved from the TCGA database. The "limma" package in R software was utilized to indicate the differentially expressed genes. For in silico functional analysis, GO and KEGG signaling pathways were conducted. PPI network was constructed based on the STRING online database by Cytoscape 3.7.2. A ceRNA network was also constructed by "GDCRNATools" package in R software. Kaplan-Meier survival analysis (log-rank test) and ROC curve analysis were used to indicate the diagnostic and prognostic values of the biomarkers. RESULTS: The differential expression data demonstrated that 2995 mRNAs, 205 lncRNAs, and 345 miRNAs were differentially expressed in COAD. The GO and KEGG pathway analysis indicated that the differentially expressed mRNAs were primarily enriched in canonical processes in cancer. The PPI network showed that the CDKN2A, CCND1, MYC, E2F, CDK4, BRCA2, CDC25B, and CDKN1A proteins were the critical hubs. In addition, the Kaplan-Meier analysis revealed that 215 mRNAs, 14 lncRNAs, and 39 miRNAs were associated with overall survival time in the patients. Also, the ceRNA network data demonstrated that three lncRNAs including MIR17HG, H19, SNHG1, KCNQ1OT1, MALAT1, GAS5, SNHG20, OR2A1-AS1, and MAGI2-AS3 genes were involved in the development of COAD. CONCLUSIONS: Our data suggested several promising lncRNAs in the diagnosis and prognosis of patients with COAD.

Combination of 5-fluorouracil and Lipopolysaccharide Synergistically Induces Cytotoxicity and Apoptosis in MCF-7 Human Breast Cancer Cells.

Several studies have been conducted to find suitable combinations of drugs to increase the efficacy of chemotherapy and reduce the resistance of tumor cells to treatment. Lipopolysaccharide (LPS), as a ligand for Toll-like receptor 4 (TLR-4), can modify immune responses in different cancers. Although multiple studies have been performed in this area, the effect of LPS on tumor cells remains controversial. In the present study, the cytotoxic effects of 5-fluorouracil (5-FU), with or without LPS, were evaluated in human breast cancer cell line (MCF-7) on apoptosis and gene expression in downstream signaling pathways. MCF-7 was obtained from the Pasteur Institute of Iran. The effects of LPS and 5-FU on cytotoxicity, apoptosis, and gene expression in NF-κB, ERK, and AKT signaling pathways were evaluated by MTT assay, Annexin V/propidium iodide (PI) apoptosis assay, and qRT-PCR, respectively. Our findings showed that LPS alone did not significantly affect cytotoxicity or apoptosis, compared to the control cells (untreated cells), while combined with 5-FU, it caused a significant increase in the apoptosis of cancer cells and decreased cell viability. It was also concluded that LPS in combination with 5-FU increased TLR-4 expression and down-regulated gene expression in NF-κB, ERK, and AKT pathways (p=0.001). Although the role of LPS in tumor inhibition or progression remains controversial, our findings suggest that LPS can be considered a novel complementary approach intranslational oncology research of breast cancer therapy.