Long noncoding RNA MAGI2‐AS3/miR‐218‐5p/GDPD5/SEC61A1 axis drives cellular proliferation and migration and confers cisplatin resistance in nasopharyngeal carcinoma

Abstract

Background: Nasopharyngeal carcinoma (NPC), a subclass of neck and head cancers, is the predominant cause of cancer-associated death globally. LncRNA MAGI2-AS3 has been previously reported to be associated with multiple cancers, but its molecular mechanism in NPC has not been fully explained. Hence, the purpose of this study is to identify the role and regulatory mechanism of MAGI2-AS3 in NPC. Methods: Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) were employed to examine gene levels. The biologic function of MAGI2-AS3 in NPC was estimated by cell counting, EdU, Transwell, and WB assays. Luciferase reporter and radioimmunoprecipitation (RIP) assays were carried out to determine the combination between miR-218-5p and MAGI2-AS3, GDPD5, and SEC61A1. Results: MAGI2-AS3 is expressed at a high level in NPC cell lines. Moreover, MAGI2-AS3 knockdown-suppressed NPC progression in vitro and in vivo. Furthermore, MAGI2-AS3 functioned as a competing endogenous RNA (ceRNA) by sponging miR-218-5p to increase the expression of GDPD5 in NPC. Importantly, it was found that MAGI2-AS3 regulated NPC progression and cisplatin resistance via modulating GDPD5. In addition, MAGI2-AS3 could also promote the proliferation and migration in NPC cells by regulating SEC61A1. Conclusion: MAGI2-AS3/miR-218-5p/GDPD5/SEC61A1 axis drove cell proliferation, migration, and epithelialmesenchymal transition, and conferred cisplatin resistance in NPC, which may provide a novel insight into the development of NPC.

Long non‑coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis

“…Several lncRNAs serve a vital role in drug resistance of NPc. For instance, lncRNA MAGI2 antisense RNA 3 conferred DDP resistance in NPC cells via regulating the microRNA (miRNA/miR)-218-5p/glycerophosphodiester phosphodiesterase domain containing 5 axis (11). lncRNA nuclear paraspeckle assembly transcript 1 promoted ddP resistance in NPc cells via the let-7a-5p/remodeling and spacing factor 1 axis (12).…”

A New Story of the Three Magi: Scaffolding Proteins and lncRNA Suppressors of Cancer

“…In contrast, MAGI2-AS3 proved to be overexpressed in gastric cancers and nasopharyngeal carcinomas [ 225 , 228 , 240 ]. MAGI2-AS3 overexpression enhances nasopharyngeal cells proliferation and migration, and their resistance to cisplatin.…”

“…MAGI2-AS3 overexpression enhances nasopharyngeal cells proliferation and migration, and their resistance to cisplatin. This process is related to miR-218-5p downregulation, leading to increased accumulation of GDPD5 (glycerophosphodiester phosphodiesterase domain containing 5) that cleaves the glycosylphosphatidylinositol anchoring proteins to the plasma membrane, and SEC61A1 (SEC61 translocon subunit α1) involved in the insertion of polypeptides into the endoplasmic reticulum [ 228 ]. In gastric cancer, MAGI2-AS3 is negatively associated with overall survival and disease-free survival of cancer patients and promotes epithelial–mesenchymal transition (EMT), cell migration, and invasiveness by sponging miR-141/200a and upregulating the ZEB1 transcription factor [ 225 ].…”

HOXA11‑AS induces cisplatin resistance by modulating the microRNA‑98/PBX3 axis in nasopharyngeal carcinoma

“…In addition, lncRNAs have been demonstrated to exert crucial roles in the chemoresistance of human cancer types, including NPC (10). For instance, lncRNA MAGI2-antisense RNA 3 contributes to the DDP resistance of NPC by regulating the microRNA (miRNA/miR)-218-5p/glycerophosphodiester phosphodiesterase domain containing 5/SEC61 translocon subunit α1 axis (11). The lncRNA long intergenic non-protein coding RNA 346 promotes DDP resistance in NPC cells by sponging miR-342 (12).…”