LY6K-AS lncRNA is a lung adenocarcinoma prognostic biomarker and regulator of mitotic progression.
14-3-3 Proteins
/ genetics
Adenocarcinoma of Lung
/ drug therapy
Animals
Antigens, Ly
/ genetics
Biomarkers, Tumor
/ genetics
Carcinogenesis
/ drug effects
Cell Proliferation
/ genetics
Cisplatin
/ pharmacology
Female
GPI-Linked Proteins
/ genetics
Gene Expression Regulation, Neoplastic
/ drug effects
Heterografts
Histones
/ genetics
Humans
Male
Mice
Mitosis
/ genetics
Prognosis
RNA, Long Noncoding
/ genetics
Transcriptome
/ genetics
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
10
11
2020
accepted:
03
02
2021
revised:
28
01
2021
pubmed:
7
3
2021
medline:
21
10
2021
entrez:
6
3
2021
Statut:
ppublish
Résumé
Recent advances in genomics unraveled several actionable mutational drivers in lung cancer, leading to promising therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors. However, the tumors' acquired resistance to the newly-developed as well as existing therapies restricts life quality improvements. Therefore, we investigated the noncoding portion of the human transcriptome in search of alternative actionable targets. We identified an antisense transcript, LY6K-AS, with elevated expression in lung adenocarcinoma (LUAD) patients, and its higher expression in LUAD patients predicts poor survival outcomes. LY6K-AS abrogation interfered with the mitotic progression of lung cancer cells resulting in unfaithful chromosomal segregation. LY6K-AS interacts with and stabilizes 14-3-3 proteins to regulate the transcription of kinetochore and mitotic checkpoint proteins. We also show that LY6K-AS regulates the levels of histone H3 lysine 4 trimethylation (H3K4me3) at the promoters of kinetochore members. Cisplatin treatment and LY6K-AS silencing affect many common pathways enriched in cell cycle-related functions. LY6K-AS silencing affects the growth of xenografts derived from wildtype and cisplatin-resistant lung cancer cells. Collectively, these data indicate that LY6K-AS silencing is a promising therapeutic option for LUAD that inhibits oncogenic mitotic progression.
Identifiants
pubmed: 33674747
doi: 10.1038/s41388-021-01696-7
pii: 10.1038/s41388-021-01696-7
doi:
Substances chimiques
14-3-3 Proteins
0
Antigens, Ly
0
Biomarkers, Tumor
0
GPI-Linked Proteins
0
Histones
0
LY6K protein, human
0
RNA, Long Noncoding
0
histone H3 trimethyl Lys4
0
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2463-2478Références
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