MicroRNA-3613-5p Promotes Lung Adenocarcinoma Cell Proliferation through a RELA and AKT/MAPK Positive Feedback Loop
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...
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2020-12-01T00:00:00Z.
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001 | doaj_5d5ccd35829a4087b10cc9a5fb4459d0 | ||
042 | |a dc | ||
100 | 1 | 0 | |a Tao He |e author |
700 | 1 | 0 | |a Hongyou Shen |e author |
700 | 1 | 0 | |a Shuangmiao Wang |e author |
700 | 1 | 0 | |a Yanfang Wang |e author |
700 | 1 | 0 | |a Zhiwei He |e author |
700 | 1 | 0 | |a Litong Zhu |e author |
700 | 1 | 0 | |a Xinyue Du |e author |
700 | 1 | 0 | |a Dan Wang |e author |
700 | 1 | 0 | |a Jiao Li |e author |
700 | 1 | 0 | |a Shizhen Zhong |e author |
700 | 1 | 0 | |a Wenhua Huang |e author |
700 | 1 | 0 | |a Huiling Yang |e author |
245 | 0 | 0 | |a MicroRNA-3613-5p Promotes Lung Adenocarcinoma Cell Proliferation through a RELA and AKT/MAPK Positive Feedback Loop |
260 | |b Elsevier, |c 2020-12-01T00:00:00Z. | ||
500 | |a 2162-2531 | ||
500 | |a 10.1016/j.omtn.2020.09.024 | ||
520 | |a 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. | ||
546 | |a EN | ||
690 | |a Therapeutics. Pharmacology | ||
690 | |a RM1-950 | ||
655 | 7 | |a article |2 local | |
786 | 0 | |n Molecular Therapy: Nucleic Acids, Vol 22, Iss , Pp 572-583 (2020) | |
787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S216225312030295X | |
787 | 0 | |n https://doaj.org/toc/2162-2531 | |
856 | 4 | 1 | |u https://doaj.org/article/5d5ccd35829a4087b10cc9a5fb4459d0 |z Connect to this object online. |