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

• Main Authors: Tao He (Author), Hongyou Shen (Author), Shuangmiao Wang (Author), Yanfang Wang (Author), Zhiwei He (Author), Litong Zhu (Author), Xinyue Du (Author), Dan Wang (Author), Jiao Li (Author), Shizhen Zhong (Author), Wenhua Huang (Author), Huiling Yang (Author)
• Format: Book
• Published: Elsevier, 2020-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Aberrant activation of nuclear factor κB (NF-κB)/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-κB 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-κB/RELA and AKT/MAPK pathways.

Item Description

2162-2531
10.1016/j.omtn.2020.09.024