Emerging Role of Non-Coding RNAs in Senescence

Abstract

Senescence is defined as a gradual weakening of functional features of a living organism. Cellular senescence is a process that is principally aimed to remove undesirable cells by prompting tissue remodeling. This process is also regarded as a defense mechanism induced by cellular damage. In the course of oncogenesis, senescence can limit tumor progression. However, senescence participates in the pathoetiology of several disorders such as fibrotic disorders, vascular disorders, diabetes, renal disorders and sarcopenia. Recent studies have revealed contribution of different classes of non-coding RNAs in the cellular senescence. Long non-coding RNAs, microRNAs and circular RNAs are three classes of these transcripts whose contributions in this process have been more investigated. In the current review, we summarize the available literature on the impact of these transcripts in the cellular senescence.

Keywords: biomarker; epigenetics; expression; lncRNA; miRNA; senescence.

FIGURE 1

Summary of the role of lncRNAs in senescence.

FIGURE 2

A schematic diagram of the role of several lncRNAs in the modulation of cellular senescence through Wnt/β-catenin signaling pathway. Accumulating evidence has illustrated that various lncRNAs are important regulatory factors in the biological aging. It has been reported that lncRNA H19 via directly targeting miR-22 could promote H2O2-induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt/β-catenin signaling cascade. Thereby, lncRNA H19 could enhance the expression levels of LEF1, c-Myc, and Cyclin D1 in NPCs (Wang et al., 2018b). Moreover, another research has figured out that lncRNA-p21 via downregulating β-catenin expression could regulate cellular senescence in mesenchymal stem cells (Xia et al., 2017). Green lines indicate the positive regulatory effect among lncRNAs and their targets, and red lines depict negative one among them.

FIGURE 3

Role of miRNAs in senescence.

FIGURE 4

A schematic diagram of the role of several miRNAs in the senescence process through regulating PI3K/AKT/mTOR signaling cascade. Mounting evidence has demonstrated that aberrant expression of various miRNAs could be correlated with cellular senescence. As an illustration, a recent study has detected that miR-221 could play a crucial role in modulating proliferation, chemotherapy sensitivity and senescence in lung cancer cells via downregulating PTEN and upregulating AKT expression levels (Wang et al., 2018c). Moreover, another research has revealed that high glucose could result in premature senescence of human glomerular mesangial cells via reducing miR-126 and p-Akt expression levels and promote in the expression of p53, p21 and Rb proteins in the high-dose d-glucose group (Cao et al., 2019). Furthermore, another study has detected that miR-21 could elevate cardiac aging induced by D-gal and Dox via suppressing PTEN (Bei et al., 2018). In addition, miR-34a-3p could enhance the senescence of dental pulp stem cells via inhibiting CAB39 expression through the AMPK/mTOR signaling pathway (Zhang et al., 2021). Green lines indicate the positive regulatory effect among miRNAs and their targets, and red lines depict negative one among them.

FIGURE 5

Role of circRNAs in senescence.