Expression and Functional Analysis of Immuno-Micro-RNAs mir-146a and mir-326 in Colorectal Cancer.

Micro-RNAs (miRNAs) are non-coding RNAs with importance in the development of cancer. They are involved in both tumor development and immune processes in tumors. The present study aims to characterize the behavior of two miRNAs, the proinflammatory miR-326-5p and the anti-inflammatory miR-146a-5p, in colorectal cancer (CRC), to decipher the mechanisms that regulate their expression, and to study potential applications. Tissue levels of miR-326-5p and miR-146a-5p were determined by qrt-PCR (real-time quantitative reverse transcription polymerase chain reaction) in 45 patients with colorectal cancer in tumoral and normal adjacent tissue. Subsequent bioinformatic analysis was performed to characterize the transcriptional networks that control the expression of the two miRNAs. The biomarker potential of miRNAs was assessed. The expression of miR-325-5p and miR-146a-5p was decreased in tumors compared to normal tissue. The two miRNAs are regulated through a transcriptional network, which originates in the inflammatory and proliferative pathways and regulates a set of cellular functions related to immunity, proliferation, and differentiation. The miRNAs coordinate distinct modules in the network. There is good biomarker potential of miR-326 with an AUC (Area under the curve) of 0.827, 0.911 sensitivity (Sn), and 0.689 specificity (Sp), and of the combination miR-326-miR-146a, with an AUC of 0.845, Sn of 0.75, and Sp of 0.89. The miRNAs are downregulated in the tumor tissue. They are regulated by a transcriptional network in which they coordinate distinct modules. The structure of the network highlights possible therapeutic approaches. MiR-326 and the combination of the two miRNAs may serve as biomarkers in CRC.

A Group of Tumor-Suppressive micro-RNAs Changes Expression Coordinately in Colon Cancer.

MicroRNAs (miRNAs) are molecules with a role in the post-transcriptional regulation of messenger RNA, being involved in a wide range of biological and pathological processes. In the present study, we aim to characterize the behavior of a few miRNAs with roles in the cell cycle and differentiation of colon cancer (CC) cells. The present work considers miRNAs as reflections of the complex cellular processes in which they are generated, their observed variations being used to characterize the molecular networks in which they are part and through which cell proliferation is achieved. Tumoral and adjacent normal tissue samples were obtained from 40 CC patients, and the expression of miR-29a, miR-146a, miR-215 and miR-449 were determined by qRT-PCR analysis. Subsequent bioinformatic analysis was performed to highlight the transcription factors (TFs) network that regulate the miRNAs and functionally characterizes this network. There was a significant decrease in the expression of all miRNAs in tumor tissue. All miRNAs were positively correlated with each other. The analysis of the TF network showed tightly connected functional modules related to the cell cycle and associated processes. The four miRNAs are downregulated in CC; they are strongly correlated, showing coherence within the cellular network that regulates them and highlighting possible approach strategies.

A role for serum cytokines and cell adhesion molecules in the non-invasive diagnosis of colorectal cancer.

Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Consequently, new diagnostic and therapeutic approaches are being investigated including the serum levels of cytokines and other molecules, although the results are often inconclusive. Thus, the present study aimed to determine whether serum level of cytokines, cell adhesion molecules or matrix metalloproteinases (MMPs), alone or in combination, may contribute to the non-invasive diagnosis of CRC. The serum levels of nine cytokines [ILs; IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22 and IL-33, and interferon (IFN)-γ], two cell adhesion molecules (intercellular adhesion molecule-1 and P-selectin) and an MMP-7 were measured by ELISA in 33 patients with CRC and 35 healthy controls. Combined capacity of all molecules to detect the presence of CRC was assessed by logistic regression. Molecules and molecule combinations were tested for all stages and tumor grades. A significant increase was identified for IL-8 in patients compared with healthy controls; IL-10 was found to be significantly decreased. The biomarker potential of each significantly modified molecule was tested: IL-8 had a sensitivity of 0.865, a specificity of 0.600 and an area under the curve (AUC) of 0.777; for IL-10, sensitivity was 0.65, specificity was 0.69, with an AUC of 0.689. Logistic regression determined the best discriminative potential between patients and control groups for the combination IL-4 + IL-6 + IL-8 + IFN-γ, with 0.97 sensitivity and 0.58 specificity. For the early stages of CRC, the combination IL-6 + IL-8 + IL-22 showed good performance. It was concluded that increased IL-8 had potential as single biomarker in CRC. Cytokine combinations are superior to single cytokine analysis in showing the presence of CRC.

An overview of the tumor microenvironment, from cells to complex networks (Review).

For a long period, cancer has been believed to be a gene disease, in which oncogenic and suppressor mutations accumulate gradually, finally leading to the malignant transformation of cells. This vision has changed in the last few years, the involvement of the tumor microenvironment, the non-malignant part of the tumors, as an important contributor to the malignant growth being now largely recognized. There is a consensus according to which the understanding of the tumor microenvironment is important as a means to develop new approaches in the therapy of cancer. In this context, the present study is a review of the different types of non-malignant cells that can be found in tumors, with their pro or antitumoral actions, presence in tumors and therapeutic targeting. These cells establish complex relations between them, through cytokines, exosomes, cell adhesion, co-stimulation and co-inhibition; these relations will also be examined in the present work.