Differential expression of long non-coding RNAs in colon cancer: Insights from transcriptomic analysis.

BACKGROUND: Colon Cancer (CC) incidence has sharply grown in recent years. Long non-coding RNAs (lncRNA) are produced by a group of non-protein-coding genes, and have important functions in controlling gene expression and impacting the biological features of various malignancies including CC. METHODS: Our research focused on examining the function of lncRNAs in the development of colon cancer. To this end, we selected and analyzed a dataset (GSE104836) from the GEO database, which contained information about the expression of mRNAs and lncRNAs in both colon cancer tissues and normal adjacent paired tumor tissues. The DESeq2 R package in Bioconductor was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) that showed differences in expression levels. Next, by literature review of previous studies, we chose two lncRNAs (FENDRR and LINC00092) for additional studies. To validate our findings, a series of tests were performed on a total of 31 tumor tissues and normal paired adjacent tumor tissues. The lncRNA expression levels were assessed in tumor tissues as well as in surrounding normal tumor tissues. RESULTS: The data confirmed that just two particular lncRNAs, FENDRR and LINC00092, had considerably decreased expression levels throughout all stages of cancer. In addition, the survival assay was conducted using the GEPIA2 software, revealing that a reduced expression of FENDRR is correlated with a reduced overall survival. Furthermore, our investigation using receiver operating characteristic (ROC) methodology revealed that these two lncRNAs had significant discriminatory ability between colon cancer and normal tissues. To determine the cause of the decrease in the activity of these two long non-coding RNAs (lncRNAs), we used methylation-specific PCR (MSP) to examine the methylation pattern of their promoter regions. Our investigation revealed hypermethylation in the promoter regions of FENDRR and LINC00092 within tumor tissues compared to normal adjacent tumor tissues. CONCLUSION: Taken together, our findings revealed the lncRNAs signatures as potential therapeutic targets and molecular diagnostic biomarkers in colon cancer. Furthermore, the evidence provided substantiates the important role of promoter methylation in regulating the expression levels for both of these lncRNAs.

The Association Between Traumatic Brain Injury and Accelerated Fracture Healing: A Study on the Effects of Growth Factors and Cytokines.

Evidence suggests that some systemic and local factors, including cytokines and growth factors in patients with traumatic brain injury (TBI), can play an essential role in accelerating fracture healing. The purpose of this study was to evaluate serum levels of some inflammatory cytokines and growth factors in patients with fracture and TBI as well as healthy subjects. In this study, a total number of 30 patients with a femoral fracture, 30 cases with TBI, 30 patients with TBI and a femoral fracture (fracture + TBI group), and 30 healthy subjects were recruited. The Glasgow Coma Scale (GCS) scores were also determined upon their admission. Then, the serum levels of fibroblast growth factor 2 (FGF-2), transforming growth factor-beta (TGF-ß), platelet-derived growth factor (PDGF), bone morphogenetic protein 2 (BMP-2), insulin-like growth factor 1 (IGF-1), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6) were measured via enzyme-linked immunosorbent assay (ELISA) technique, 12 h and 4 weeks after injury and hospital admission. The study results demonstrated that the serum levels of BMP-2, FGF-2, IL-1ß, and PDGF in the femoral fracture + TBI group increased significantly over 12 h and after 4 weeks compared with other groups, but the serum levels of IGF-I, IL-6, and TGF-ß in this group increased in a significant manner at 12 h compared with other studied groups. The findings also showed that the time to union of a femoral fracture was shorter in the fracture + TBI group than in cases with a femoral fracture alone (p = 0.03). Accordingly, it seems that elevated serum levels of BMP-2, PDGF, FGF-2, and IL-1ß may be associated with healing acceleration in fracture + TBI patients. However, further studies are needed to confirm this claim.

Vanadium complex: an appropriate candidate for killing hepatocellular carcinoma cancerous cells.

Hepatocellular carcinoma (HCC) is a prevalent human malignancy which its drug resistance is increasing world-wide. This project was designed to assess the anti-cancer effects of 4-bromo-2-(((5-chloro-2-hydroxyphenyl) imino) methyl) phenol ([IV(L)] complex) on the HepG2 cell line and also L929 cells, as normal cells. HepG2 and L929 cells were cultured in RPMI culture medium and the survival rates of the cells were determined after 24 and 48 h using MTT assay to find IC50 concentration of vanadium m, [IV(L)] complex. The early apoptosis and necrosis/late apoptosis were determined by means of annexin V/PI apoptosis detection kit. The results revealed that vanadium m, [IV(L)] complex induce early apoptosis higher in HepG2 cell line than L929 cells. The rates of necrosis/late apoptosis were also induced in HepG2 cells more than L929 cells. Based on the results, vanadium m, [IV(L)] complex might be considered as a safe new drug for treatment of HCC with low side effects on control liver cells.

Persian shallot, Allium hirtifolium 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.