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Long non-coding RNA ANRIL promotes homologous recombination-mediated DNA repair by maintaining ATR protein stability to enhance cancer resistance

Lei Liu, Yuan-Yuan Chen, Yi-Juan Huang, Kun Cao, Ting-Ting Liu, Hui Shen, Jian-Guo Cui, Bai-Long Li et al.

Molecular Cancer, 2021

42 citations

Abstract

Main text Aberrantly enhanced DNA damage repair leads to therapeutic resistance in many types of cancer [1, 2]. Recently, long non-coding RNAs (lncRNAs) have been shown as indispensable participants in DNA damage repair and provide novel targets for overcoming cancer resistance [3, 4]. However, the exact roles of most lncRNAs in DNA damage repair remain largely unknown. Here, we present our novel finding that lncRNA ANRIL promotes cancer resistance by mediating homologous recombination (HR) repair of DNA damage. ANRIL promoted HR repair to enhance cancer resistance to DNA damage treatments in lung cancer cells Lung cancer with high ANRIL expression is a leading cause of mortality worldwide and was chosen as a model to investigate the role of ANRIL in DNA damage repair and therapeutic resistance [5]. First, significant elevation of ANRIL was found in lung cancer tissues compared with that in adjacent normal tissues from 80 pairs of clinical specimens (Fig. S1A). High expression of ANRIL was also confirmed in lung cancer cells compared with that in normal BEAS-2B cells (Fig. S1B). Through analyzing data from TCGA database, ANRIL was also found to be upregulated in lung squamous cell carcinoma, but not adenocarcinoma (Fig. S1K). Moreover, ANRIL expression was greatly increased by ionizing radiation (IR) and other DNA damaging reagents, such as etoposide and camptothecin (CPT) (Fig. S1C-F), which was supported by the results of a previous study [6]. Then, genetically modified…

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