LncRNA LOC105378097 inhibits cardiac mitophagy in natural ageing mice

Abstract

1) The heart-enriched lncR-SMAL is robustly increased in its level in serum samples of human subjects over 60-year old relative to young controls, and in both nucleus and cytoplasm of senescent cardiomyocytes. (2) Artificial overexpression of lncR-SMAL induces cardiac senescence by inhibiting Parkinmediated mitophagy. Knockdown of endogenous lncR-SMAL in cardiomyocytes partially abrogated cell senescence. (3) LncR-SMAL interacts with Parkin protein and promotes ubiquitin-proteasome degradation of Parkin in senescent cardiomyocytes.

M1 macrophage-derived extracellular vesicle containing tsRNA-5006c promotes osteogenic differentiation of aortic valve interstitial cells through regulating mitophagy

“…Regrettably, the function of M1-EVs tsRNA-5006c on mitophagy was not verified in animals, and the relevant studies are now too few to support our conclusion. Perhaps, studies on the regulation of mitophagy by noncoding RNAs can partially support our results such as miR-155 ( Tsujimoto et al, 2020 ) and lncRNA LOC105378097 ( Liu et al, 2022a ). For instance, promoting AMPK-mediated mitophagy mediated by miRNA-134-5p knockdown could rescue dendritic deficits in a mouse model of depression ( Wang et al, 2022a ).…”

Bibliometric analysis of trends in cardiac aging research over the past 20 years

“…Senescence-mitophagy associated long noncoding RNA overexpressed hearts showed a significant increase in SASP compared with healthy hearts, suggesting that noncoding RNA has therapeutic potential in treating cardiac aging. [44] "Parkin" and "melatonin" also play a role in improving cardiac aging by improving mitochondrial autophagy and reducing oxidative stress damage and inflammation. [45,46] There is evidence to support regeneration of aging myocardium, and apoptotic heart cells can be replaced by new cells derived from cardiac stem cells/progenitor cells.…”

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

“…In mouse models in vivo , lncRNA LOC105378097 suppressed cardiomyocyte mitophagy and induced heart aging by promoting Parkin ubiquitination and reducing Parkin protein stability ( 69 ) ( Figure 4 ). CircHIPK3 attenuates heart aging by promoting the binding of E3 ubiquitin ligase β-TrCP to HuR, enhancing ubiquitination and degradation of HuR and ultimately decreasing the activity of p21 in mice in vivo and in vitro ( 70 ).…”

“…LncRNA LOC105378097, circDLGAP4, miR-140-5p, miR-424(322), miR-146-5p, circ-UBR4 and miR-29a are considered diagnostic indicators of heart aging, ischemic stroke, PAH and atherosclerosis ( Table 1 ). LncRNA LOC105378097 is upregulated in the serum of patients with heart aging, which indicates a high diagnostic value ( 69 ). Downregulated circDLGAP4 has potential diagnostic significance by sampling plasma from ischemic stroke patients ( 89 ).…”

“…Unlike the ncRNAs mentioned above, which directly exert protective effects on hearts and blood vessels, many ncRNAs are suppressed to improve CVDs by regulating UPS components. For instance, knockdown of ncRNAs was considered a promising therapeutic strategy for the treatment of heart diseases by suppressing ubiquitination degradation of proteins (miRNA-1, circNfix, miR‐195‐5p, lncRNA LOC105378097, lncDACH1) or promoting ubiquitination enzyme expression (miR-30a, miR-21) ( 47 , 49 , 57 , 62 , 63 , 66 , 69 ). Silencing of miRNA-1 and circNfix plays important roles in inhibiting cardiomyocyte apoptosis and alleviating the MI process by inhibiting UPS components/Nedd4l ( 47 , 49 ).…”