Downregulation of KIAA1199 by miR-486-5p suppresses tumorigenesis in lung cancer.
KIAA1199
Non-small cell lung cancer (NSCLC)
cell motility
cell proliferation
miR-486-5p
microRNA
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
13
03
2020
revised:
13
05
2020
accepted:
22
05
2020
pubmed:
11
6
2020
medline:
3
6
2021
entrez:
11
6
2020
Statut:
ppublish
Résumé
Lung cancer is the primary cause of death among cancer patients in China, among which nonsmall cell lung cancer (NSCLC) makes up the great majority. Hence, it is imperative to identify the biomarkers and mechanisms involved in NSCLC oncogenesis. Our present research found that KIAA1199 expression was significantly increased in NSCLC and closely related to cell proliferation, motility, and poor prognosis. We demonstrated that knockdown of KIAA1199 reduced NSCLC cell growth and motility in vitro whereas overexpression of KIAA1199 had the opposite effect. Inhibition of KIAA1199 significantly suppressed tumor growth in mouse NSCLC xenograft models. Mechanistically, as an epidermal growth factor receptor (EGFR)-binding protein, KIAA1199 promotes EGFR signaling and regulates EGFR-dependent Src, Erk, and Akt phosphorylation, as well as downstream kinases in the EGF-mediated EMT pathway. We demonstrated that KIAA1199 can function as a direct binding target for miR-486-5p and that miR-486-5p overexpression can attenuate proliferation and migration of NSCLC cells via regulating the EGFR signaling pathways. To conclude, our results defined KIAA1199 as an oncogenic protein that promotes cancer cell proliferation and migration by regulating EGF-mediated signaling pathways. This study provided new insight into NSCLC oncogenesis, which could lead to the development of innovative therapeutic plans for NSCLC.
Identifiants
pubmed: 32519472
doi: 10.1002/cam4.3210
pmc: PMC7402811
doi:
Substances chimiques
MIRN486 microRNA, human
0
MicroRNAs
0
CEMIP protein, human
EC 3.2.1.35
Hyaluronoglucosaminidase
EC 3.2.1.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5570-5586Informations de copyright
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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