LY6K-AS LncRNA is a Lung Adenocarcinoma Prognostic Biomarker and Regulator of Mitotic Progression

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2021 Mar 6

PMID 33674747

Citations 16

Authors

Mohamad Moustafa Ali

Mirco Di Marco

Sagar Mahale

Daniel Jachimowicz

Subazini Thankaswamy Kosalai

Silke Reischl

Luisa Statello

Kankadeb Mishra

Catarina Darnfors

Meena Kanduri

Chandrasekhar Kanduri

Affiliations

Soon will be listed here.

Abstract

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.

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