lncRNA LINC02446 通过调控 EBV-NK-LPDs 中 KLRs 与 IL-10 的表达促进肿瘤进展及 HLH 发生

Here, we investigated long non-coding RNA (lncRNA) profile using high-throughput RNA sequencing data (n = 6, healthy donors; n = 5, infectious mononucleosis; n = 10, chronic active Epstein-Barr virus disease (CAEBV)-NK; n = 7, CAEBV-T) and screened out LINC02446, whose upregulation was further validated by quantitative real-time polymerase chain reaction in EBV-NK-LPDs. We further explored the correlation between LINC02446 and the clinical characteristics of patients with EBV-NK-LPDs. Then, based on sequencing data, we performed in vitro experiments to investigate the function and mechanism of LINC02446 in EBV-NK-LPDs.

LINC02446 was specifically highly expressed in NK cells of EBV-NK-LPDs patients. EBV-NK-LPDs patients with high expression of LINC02446 showed higher EBV-DNA copy number and ferritin levels, as well as a higher incidence of HLH. LINC02446 was closely related to the KLRs family and LINC02446 could regulate the expression of KLRs genes. In addition, LINC02446 positively regulated the expression of IL-10 in EBV-NK-LPDs cell lines, which revealed that LINC02446 may promote HLH by upregulating IL-10 in EBV-NK-LPDs.

This is the first study that LINC02446 regulates the expression of KLRs family and IL-10 in EBV-NK-LPDs, resulting in lymphoma progression and HLH occurrence, showing its potential as a therapeutic target for EBV-NK-LPDs.