Knockdown of lncRNA MCM3AP-AS1 Attenuates Chemoresistance of Burkitt Lymphoma to Doxorubicin Treatment via Targeting the miR-15a/EIF4E Axis

Cancer Manag Res. 2020 Jul 16;12:5845-5855. doi: 10.2147/CMAR.S248698. eCollection 2020.

Abstract

Purpose: The long-noncoding RNA MCM3AP-AS1 has been shown to participate in the tumorigenesis and growth of several types of cancer, but little is known about the role of MCM3AP-AS1 in the chemoresistance of lymphoma.

Methods: A series of patients with Burkitt lymphoma were enrolled for clinical analysis. Daudi and Namalwa cells were used for further experiments. CCK-8 and apoptosis assays were used to assess the response to doxorubicin. Mitochondrial membrane potential assays and high-resolution respirometry were used to assess mitochondrial function. Western blotting was used to detect the expression of certain molecules. Luciferase assays and microRNA transfection were used to clarify the regulatory mechanisms of MCM3AP-AS1. An in vivo model using BALB/c nude mice was utilized to investigate the effects of MCM3AP-AS1 on cell proliferation and tumor growth.

Results: The expression level of MCM3AP-AS1 was increased in tumors compared with normal lymph nodes, which indicated poor prognosis in patients with Burkitt lymphoma. Moreover, compared with siNC transfection, MCM3AP-AS1 knockdown decreased cell viability and increased apoptosis rates upon doxorubicin treatment compared with siNC. Further studies indicated that upregulation of several antiapoptotic factors, downstream of EIF4E, was partially responsible for MCM3AP-AS1-induced chemoresistance. Moreover, miR-15a functioned as a link between MCM3AP-AS1 and EIF4E, and was sponged by MCM3AP-AS1. Finally, we showed that the MCM3AP-AS1/miR-15a/EIF4E axis regulated the chemoresistance of lymphoma cells in vitro and in vivo.

Conclusion: MCM3AP-AS1/miR-15a/EIF4E axis plays a role in the chemoresistance of Burkitt lymphoma, and it might become a promising target for lymphoma therapeutics.

Keywords: Burkitt lymphoma; EIF4E; MCM3AP-AS1; chemosensitivity; microRNA-15a.