Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 2)

One of the cellular processes influenced by microRNAs is senescence, a state of indefinite growth arrest triggered by sublethal cell damage. Here, through bioinformatic analysis and experimental validation, we identified miR-340-5p as a novel miRNA that foments cellular senescence. miR340-5p was highly abundant in diverse senescence models, and miR-340-5p overexpression in proliferating cells rendered them senescent. Among the target mRNAs, miR-340-5p prominently reduced the levels of LBR mRNA, encoding Lamin B Receptor (LBR). Loss of LBR by ectopic overexpression of miR-340-5p derepressed heterochromatin in lamina-associated domains (LADs), promoting the expression of DNA repetitive elements characteristic of senescence. Importantly, overexpressing miR-340-5p enhanced cellular sensitivity to senolytic compounds, while antagonization of miR-340-5p reduced senescent-cell markers and engendered resistance to senolytic-induced cell death. We propose that miR-340-5p can be exploited for clearing senescent cells to restore tissue homeostasis and mitigate damage by senescent cells in aging human pathologies.