MicroRNA-3613-5p Promotes Lung Adenocarcinoma Cell Proliferation through a RELA and AKT/MAPK Positive Feedback Loop.

ABSTRACT: Aberrant activation of nuclear factor ?B (NF-?B)/RELA is often found in lung adenocarcinoma (LUAD). In this study, we determined that microRNA-3613-5p (miR-3613-5p) plays a crucial role in RELA-mediated post-transcriptional regulation of LUAD cell proliferation. Expression of miR-3613-5p in clinical LUAD specimens is associated with poor prognosis in LUAD. Upregulation of miR-3613-5p promotes LUAD cell proliferation in vitro and in vivo. Our results suggested a mechanism whereby miR-3613-5p expression is induced by RELA through its direct interaction with JUN, thereby stimulating the AKT/mitogen-activated protein kinase (MAPK) pathway by directly targeting NR5A2. In addition, we also found that phosphorylation of AKT1 and MAPK3/1 co-transactivates RELA, thus constituting a RELA/JUN/miR-3613-5p/NR5A2/AKT1/MAPK3/1 positive feedback loop, leading to persistent NF-?B activation. Our findings also revealed that miR-3613-5p plays an oncogenic role in LUAD by promoting cell proliferation and acting as a key regulator of the positive feedback loop underlying the link between the NF-?B/RELA and AKT/MAPK pathways.

SUBMITTER: He T 

PROVIDER: S-EPMC7562961 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature