Abstract
Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma. Currently, only a few gene rearrangements have been linked to ALK-negative ALCL progression. However, the specific molecular mechanisms underlying the growth of ALK-negative ALCL tumors remain unclear. Here, we investigated aberrantly expressed, long non-coding RNAs (lncRNAs) in ALK-negative ALCL and assessed their potential biological function. MIR503HG (miR-503 host gene) was highly expressed in ALK-negative cell lines and was significantly upregulated in tumors in mice formed from ALK-negative ALCL cell lines. Depletion of MIR503HG suppressed tumor cell proliferation in vivo and in vitro; conversely, its overexpression enhanced tumor cell growth. MIR503HG-induced proliferation was mediated by the induction of microRNA-503 (miR-503) and suppression of Smurf2, resulting in stabilization of the tumor growth factor-β receptor (TGFBR) and enhanced tumor cell growth. Collectively, these findings support a potential role for MIR503HG in cancer cell proliferation through the miR-503/Smurf2/TGFBR axis and indicate that MIR503HG is a potential marker in ALK-negative ALCL.
Highlights
Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a highly malignant non-Hodgkin lymphoma of CD30-positive T-cells that lacks chromosomal rearrangements of the ALK gene encoding a receptor tyrosine kinase [1,2,3]
Our data indicate that MIR503HG plays an oncogenic role in ALK-negative ALCL by inducing miR-503 expression; this increase in miR-503 leads to Smurf2 degradation and transforming growth factor beta receptor (TGFBR) stabilization and promotes cell proliferation
The specific pathways involved in ALK-negative ALCL proliferation and the pivotal role of aberrantly expressed MIR503HG in ALK-negative ALCL was validated using an in vivo mouse model
Summary
Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a highly malignant non-Hodgkin lymphoma of CD30-positive T-cells that lacks chromosomal rearrangements of the ALK gene encoding a receptor tyrosine kinase [1,2,3]. The Nucleophosmin (NPM)-ALK fusion protein resulting from translocation involving the ALK gene on 2p23, as well as the oncogenic role of these fusion proteins, has been studied extensively in ALK-positive ALCL [4,5,6]. The pathogenic mechanism of ALK-negative ALCL is poorly understood. It is difficult to distinguish ALK-negative ALCL from other CD30-positive peripheral T-cell lymphomas (PTCLs) because genetic biomarkers are lacking. Ferreri et al reported that survival rates are higher in patients with ALK-positive ALCL than in ALK-negative patients [7].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
