The long non-coding RNA LINC01013 enhances invasion of human anaplastic large-cell lymphoma

I-Hsiao Chung,Kwang-Huei Lin,Yun-Wen Lin,Yang-Hsiang Lin,Chau-Ting Yeh,Pei-Hsuan Lu,Ming-Ming Tsai

doi:10.1038/s41598-017-00382-7

Abstract

Anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma (NHL). Currently, only studies on the chimeric oncogene NPM-ALK have reported a link to ALCL progression. However, the specific molecular mechanisms underlying the invasion of ALCL are still unclear. Here, we sought to investigate differentially expressed, long non-coding RNAs (lncRNAs) in ALCL and their potential biological function. Our microarray analyses revealed that LINC01013, a novel non-coding RNA gene, was highly expressed in clinical specimens of ALCL and was significantly upregulated in invasive ALCL cell lines. Knockdown of LINC01013 suppressed tumor cell invasion; conversely, its overexpression enhanced tumor cell invasion. LINC01013-induced invasion was mediated by activation of the epithelial-to-mesenchymal transition (EMT)-associated proteins, snail and fibronectin. Specifically, LINC01013 induced snail, resulting in activation of fibronectin and enhanced ALCL cell invasion. Collectively, these findings support a potential role for LINC01013 in cancer cell invasion through the snail-fibronectin activation cascade and suggest that LINC01013 could potentially be utilized as a metastasis marker in ALCL.

Highlights

The majority of ALK(+) Anaplastic large-cell lymphoma (ALCL) cases are diagnosed at advanced stages (III and IV) that display systemic disease with generalized lymphadenopathy and extranodal metastasis, especially in the skin and in soft tissues, such as the liver, lung, and spleen[6]
We found that several long noncoding RNAs (lncRNAs) genes were highly expressed in ALCL clinical specimens and hypothesized that their functions were associated with cancer progression
We investigated these overexpressed lncRNAs for their potential function in ALCL progression, focusing on the top five non-coding genes, BMS1P20, LINC01013, MIR503HG, RNF144A-AS1 and CACNA1G-AS1 (Table 1)

Summary

Introduction

The majority of ALK(+) ALCL cases are diagnosed at advanced stages (III and IV) that display systemic disease with generalized lymphadenopathy and extranodal metastasis, especially in the skin and in soft tissues, such as the liver, lung, and spleen[6]. We found that several lncRNA genes were highly expressed in ALCL clinical specimens and hypothesized that their functions were associated with cancer progression. Our microarray analysis revealed that LINC01013 (long intergenic non-protein–coding RNA 1013), a novel lncRNA that has not been linked to human cancer in the literature, is overexpressed in clinical specimens of ALCL and is significantly up-regulated in invasive ALK(+) ALCL cell lines.

Results

Conclusion