TP73-AS1 promotes malignant progression of NK/T cell lymphoma by regulating DKK1 methylation.

PURPOSE

Long non-coding RNA (lncRNA) TP73-AS1 is abnormally expressed in multiple types of tumors, which is able to mediate tumor cell signals. This study aims to explore the role of TP73-AS1 in affecting biological functions of NK/T-cell lymphoma (NKTCL) and DKK1 methylation.

METHODS

TP73-AS1 levels in peripheral blood of NKTCL patients and healthy volunteers was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After knockdown of TP73-AS1, proliferative and migratory abilities in SNK-6 and HANK-1 cells were assessed by cell counting kit-8 (CCK-8) and Transwell assay, respectively. Regulatory effect of TP73-AS1 on DKK1 methylation in NKTCL cells was evaluated through methylation-specific PCR (MSP), dual-luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP). Rescue experiments were conducted to further validate the interaction between TP73-AS1 and DKK1.

RESULTS

TP73-AS1 level was higher in peripheral blood of NKTCL patients than that of healthy volunteers. Knockdown of TP73-AS1 in vitro weakened proliferative and migratory functions of NKTCL cells. TP73-AS1 induced methylation of DKK1 promoter through DNMT1/DNMT3, thus regulating NKTCL cell functions.

CONCLUSIONS

TP73-AS1 level was higher in peripheral blood of NKTCL patients. Through inducing methylation of DKK1 promoter, TP73-AS1 aggravates the malignant progression of NKTCL.