MicroRNA-155 is a potential molecular marker of natural killer/T-cell lymphoma

Xudong Zhang,Lifeng Li,Ruixia Huang,Weiguo Ji,Zhaoming Li,Xinhua Wang,Qingjiang Chen,Zhenchang Sun,Ling Li,Xiaorui Fu,Mingzhi Zhang

doi:10.18632/oncotarget.10780

Abstract

Natural killer/T-cell lymphoma (NKTCL) is characterized by its highly aggressive nature and rapid progression. MicroRNAs (miRNAs) play key roles in the development of NKTCL. We utilized next-generation Solexa high-throughput sequencing to compare miRNA expression in the SNK-6 and YTS NKTCL cell lines with expression in normal NK cells. We found that 195 miRNAs were upregulated in the SNK-6 cells and 286 miRNAs were upregulated in the YTS cells. Based on those results, we selected six miRNAs, including miRNA-155, and confirmed their expression using real-time polymerase chain reaction. Expression of miRNA-155 was higher in SNK-6 and YKS cells than in normal NK cells. We next determined the levels of miRNA-155 in the serum of healthy individuals and NKTCL patients, and correlated its expression with clinical parameters and inflammatory factors detected using enzyme-linked immunoabsorbent assays. Levels of miRNA-155 were higher in NKTCL patients’ serum than in serum from healthy individuals. miRNA-155 expression was higher in patients with stable or progressive disease (SD+PD) than in those with partial or complete remission (PR+CR). While further studies are needed to clarify the underlying molecular mechanisms, it appears miRNA-155 may be a molecular marker of NKTCL.

Highlights

Natural killer/T-cell lymphoma (NKTCL) is a subtype of non-Hodgkin’s lymphoma, which has a high incidence in East Asia and Latin America but a low incidence in the United States and Europe [1]
A previous study showed that, www.impactjournals.com/oncotarget www.impactjournals.com/oncotarget along with protein kinase JNK and transcriptional regulators, such as NF-kappa B and AP-1, and the stimulation of inflammatory mediators, the expression of miRNA-155 in mature B and T lymphocytes rapidly increased. This increase suggested that miRNA-155 is important for the biological functions of lymphocytes [13]. miRNA-155 is one of the first miRNAs to be confirmed to promote cancer
It is highly expressed in most blood system malignant tumors, such as diffuse large B-cell lymphoma, adult T-cell leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, Burkitt’s lymphoma, and mantle cell lymphoma, as well as in some solid tumors, such as lung cancer and breast cancer [1417]

Summary

Introduction

Natural killer/T-cell lymphoma (NKTCL) is a subtype of non-Hodgkin’s lymphoma, which has a high incidence in East Asia and Latin America but a low incidence in the United States and Europe [1]. The nasal form accounts for 70%–90% of the incidence of extranodal NKTCL, the most common category of NKTCL [2]. This tumor is characterized by its highly aggressive nature, rapid progression, short survival time, and poor prognosis [3]. MicroRNAs (miRNAs) are a hot research topic in the field of lymphoma molecular biology Among their many functions, miRNAs regulate the expression of genes involved in tumor growth and development [4]. MiRNA-21 and miRNA-155 are highly expressed in NKTCL cell lines where they activate the AKT signaling pathway to downregulate tumor suppressor genes, leading to tumor cell proliferation [5]. The unusual expression of some miRNAs was found www.impactjournals.com/oncotarget to be associated with signaling pathways that affect tumor growth and proliferation, such as MYC activation [9] and Epstein–Barr (EB) virus infection [10]

Methods

Results

Conclusion