MTMR2 promotes the progression of NK/T cell lymphoma by targeting JAK1
Authors: X-R Ma
Y Yang
X-M Cao
W-G Zhang
W-H Zhao
J Wang
Y-X Chen
H-L Liu
J Liu
J-L Wang
A-L He
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MTMR2; NK/T cell lymphoma; clinical parameters; prognosis; qRT-PCR
Affiliations: Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. .

Abstract:  Objective: The aim of this study was to investigate the expression characteristics of MTMR2 in NK/T cell lymphoma (NKTCL), and to further study its relationship with clinical parameters and the prognosis of patients with NKTCL. In addition, the potential mechanisms of MTMR2 promoting the progression of NKTCL was further explored. Materials and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine MTMR2 level in peripheral blood of 45 patients with NK/T-cell lymphoma and 45 healthy volunteers. The interplay between MTMR2 expression and clinical indicators, as well as the prognosis of patients with NK/T-cell lymphoma was analyzed. Meanwhile, MTMR2 expression in NKTCL cell lines was verified by qRT-PCR. Subsequently, MTMR2 knockdown and the overexpression models were constructed using lentivirus in NKTCL cell lines, including SNK-6 and KHYG-1. Transwell invasion and cell wound healing assays were applied to analyze the effect of MTMR2 on the biological function of NKTCL cells. Finally, an in-depth study of the relationship between MTMR2 and JAK1 was conducted to explore the underlying mechanism. Results: QRT-PCR results showed that the expression level of MTMR2 in the serum of patients with NKTCL was remarkably higher than that of healthy volunteers, and the difference was statistically significant (p&lt;0.05). Compared with patients with low expression of MTMR2, patients with high expression of MTMR2 exhibited significantly higher incidence of distant metastasis and lower overall survival rate (p&lt;0.05). The metastasis ability of NKTCL SNK-6 cells was remarkably attenuated in MTMR2 knockdown group when compared with the negative control sh-NC group (p&lt;0.05). Meanwhile, the metastatic ability of NKTCL KHYG-1 cells in MTMR2 overexpressing group was remarkably enhanced when compared with the control NC group (p&lt;0.05). The Luciferase reporter gene assay confirmed that MTMR2 could target JAK1, thereby jointly regulating the malignant progression of NKTCL. In addition, cell recovery experiment verified that JAK1 could partially reverse the enhanced metastatic ability of NKTCL cells induced by the overexpression of MTMR2. Conclusions: MTMR2 was highly expressed in NKTCL serum samples and cell lines, leading to high risk of distant metastasis and poor prognosis. In addition, MTMR2 might promote the malignant progression of NKTCL by regulating JAK1. 

Retracted: No

PubPeer comments:
 Fig 1. The column headings promise to express the numbers in each patient subgroup as percentages, but the body of the table reneges on this promise.  In itself this would be a minor error, but table 1s of this form are one characteristic feature of a  Comb papermill . Another recurring feature is pairs of Kaplan-Meier plots, crenellated along the survival curves so that they resemble combs or walls made of Lego, with survival nose-diving precipitously as time approaches 75 months. Here, Fig 1D.  ,