MiR-200-3p Is Potentially Involved in Cell Cycle Arrest by Regulating Cyclin A during Aestivation in Apostichopus japonicus

Abstract

The sea cucumber (Apostichopus japonicus) has become a good model organism for studying environmentally induced aestivation in marine invertebrates. We hypothesized that mechanisms that arrest energy-expensive cell cycle activity would contribute significantly to establishing the hypometabolic state during aestivation. Cyclin A is a core and particularly interesting cell cycle regulator that functions in both the S phase and in mitosis. In the present study, negative relationships between miR-200-3p and AjCA expressions were detected at both the transcriptional and the translational levels during aestivation in A. japonicus. Dual-luciferase reporter assays confirmed the targeted location of the miR-200-3p binding site within the AjCA gene transcript. Furthermore, gain- and loss-of-function experiments were conducted in vivo with sea cucumbers to verify the interaction between miR-200-3p and AjCA in intestine tissue by qRT-PCR and Western blotting. The results show that the overexpression of miR-200-3p mimics suppressed AjCA transcript levels and translated protein production, whereas transfection with a miR-200-3p inhibitor enhanced both AjCA mRNA and AjCA protein in A. japonicus intestine. Our findings suggested a potential mechanism that reversibly arrests cell cycle progression during aestivation, which may center on miR-200-3p inhibitory control over the translation of cyclin A mRNA transcripts.

The OxymiR response to oxygen limitation: a comparative microRNA perspective

“…Changing global climates are currently threatening their populations in northern China, forcing them to rapidly adjust to non-ideal higher summer temperatures, lower salinity and, of relevance to our review, limited oxygen availability (Plagányi et al, 2013;Huo et al, 2017). Previous work has examined the miRNA responses of sea cucumbers during estivation (see Glossary; Chen et al, 2013;Chen and Storey, 2014;Wang et al, 2019), and Huo and colleagues built on these results by using high-throughput sequencing to examine miRNA responses to hypoxia in the sea cucumber respiratory tree, an organ used for oxygen extraction (Huo et al, 2017). Of the 26 miRNAs differentially expressed (12 up-regulated and 14 down-regulated) during severe hypoxia, a subset are associated with hypoxia-adaptive mechanisms important for redox, transcription, small molecule and ion transport, and hydrolysis (Huo et al, 2017).…”

Cancer Cell Inhibiting Sea Cucumber (Holothuria leucospilota) Protein as a Novel Anti-Cancer Drug

“…The sulfated polysaccharide isolated from sea cucumber Stichopus japonicus on the 6-hydroxydopamine-induced apoptosis in SH-SY5Y cells (a human dopaminergic neuroblastoma cell line) significantly elevated protein levers of Cyclin D3 [47]. It has been reported that, in sea cucumber (Apostichopus japonicus), regulating Cyclin A could arrest cell cycle progression [48]. In HepG2, A549, and Panc02 cells, the effects of the distribution of cell cycle by H. leucospilota protein may be associated with several cyclins, cyclin-dependent kinases and other regulatory mechanisms.…”

Ginsenoside Rb1 Attenuates Triptolide-Induced Cytotoxicity in HL-7702 Cells via the Activation of Keap1/Nrf2/ARE Pathway

“…It has been reported that p53 mediates oxidative stress in cells with irreparable DNA damage, and induces apoptosis in concert with other apoptotic proteins e.g., Bax ( Hori et al, 2013 ). The combination of cyclin A and CDK2 or CDK1 regulates S phase and mitosis ( Wang et al, 2019b ). Cyclin E-CDK2 complex regulates the duplication of intracellular chromosomes which promote the entry of cells into the S phase, and on entering the G2 phase, there is a gradual decrease in cyclin E content ( Shang et al, 2020 ).…”

“…However, HL-7702 cell viability was increased after treatment with ginsenoside Rb1, indicating, significant attenuation of TP-induced cytotoxic effect on the cells. Apoptosis is triggered by exogenous and endogenous pathways, and the caspase family plays a crucial role in both pathways (Shao et al, 2019;Wang et al, 2019b). Fas is one of the most typical death receptors in the exogenous death receptor- (Xu et al, 2020).…”