MicroRNA-210 induces apoptosis in colorectal cancer via induction of reactive oxygen.

Katrin E Tagscherer,Anne Fassl,Stephan Macher-Goeppinger,Tabea Sinkovic,Sabrina Schecher,Wilfried Roth,Jutta Richter

doi:10.1186/s12935-016-0321-6

Abstract

BackgroundDeregulation of miRNA-210 is a common event in several types of cancer. However, increased expression levels in the cancer tissue have been associated with both poor and good prognosis of patients. Similarly, the function of miR-210 with regard to cell growth and apoptosis is still controversial.MethodsOverexpression of miR-210 was performed in HCT116, SW480 and SW707 colorectal cancer (CRC) cell lines. Functional effects of a modulated miR-210 expression were analyzed with regard to proliferation, clonogenicity, cell cycle distribution, reactive oxygen species (ROS) generation, and apoptosis. Furthermore, quantitative real time (RT)-PCR and immunoblot analyses were performed to investigate signaling pathways affected by miR-210.ResultsWe show that in CRC cells miR-210 inhibits clonogenicity and proliferation which was accompanied by an accumulation of cells in the G2/M phase of the cell cycle. Additionally, overexpression of miR-210 results in an increase of ROS generation. Moreover, miR-210 mediated the induction of apoptosis which was associated with an upregulation of pro-apoptotic Bim expression and enhanced processing of Caspase 2. Importantly, inhibition of ROS generation rescued cells from miR-210-induced apoptosis.ConclusionsTaken together, miR-210 induces apoptosis in CRC cells via a ROS-dependent mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0321-6) contains supplementary material, which is available to authorized users.

Highlights

Deregulation of miRNA-210 is a common event in several types of cancer
Whereas some studies show that downregulation of miR-210 reduces viability in renal cell carcinoma [10], endothelial cells [32] and hepatoma [33], other studies claim that miR-210 acts in a pro-apoptotic manner in neuroblastoma [34], lung adenocarcinoma [35], renal cell carcinoma [36], esophageal squamous carcinoma [21] and lung adenocarcinoma [37]
Whereas some studies show that downregulation of miR-210 reduces viability in renal cell carcinoma [10], endothelial cells [32] and hepatoma [33], other studies claim miR-210 to act in a pro-apoptotic manner [21, 34,35,36,37]

Summary

Introduction

Deregulation of miRNA-210 is a common event in several types of cancer. In the case of CRC this resistance to radio- and chemotherapy substantially contributes to a poor prognosis. A better understanding of the regulation of survival and therapy resistance of CRC cells is urgently required. MicroRNAs (miRNAs) are short (20–23 nucleotides) non-coding mRNA molecules [2] functioning as posttranscriptional regulators of gene expression. Since miRNAs contribute to the regulation of different cellular processes involving apoptosis, cell cycle regulation and differentiation, their deregulation quite often results in tumorigenesis [3]. The resulting microRNA precursor molecules (premiRNAs) are subsequently transported into the cytoplasm and processed to the mature miRNA by the Dicer complex [4]. 1400 human miRNAs have been discovered, amongst them almost 400 to be deregulated in CRC [6] Approx. 1400 human miRNAs have been discovered, amongst them almost 400 to be deregulated in CRC [6]

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