Cardiovascular diseases have high morbidity and mortality rates worldwide, and their treatment and prevention are challenging. MicroRNAs are a series of noncoding RNAs with highly conserved sequences and regulate gene expression by inhibiting mRNA transcription or degrading targeting proteins. MicroRNA-210 is significantly upregulated during hypoxia and plays a protective role by inhibiting apoptosis and regulating cell proliferation, differentiation, migration, mitochondrial metabolism, and angiogenesis in hypoxic cells. MicroRNA-210 expression is altered in cardiovascular diseases such as atherosclerosis, acute myocardial infarction, preeclampsia, aortic stenosis, and heart failure, and overexpression of microRNA-210 in some of these diseases exerts protective effects on target organs. Furthermore, chronically upregulated miR-210 potentially plays a marked pathogenic role in specific situations. This review primarily focuses on the upstream pathways, downstream targets, clinical progress in cardiovascular disease, and potential applications of microRNA-210.

Endothelial cell damage caused by oxidative stress is widely considered to be a triggering event in atherosclerosis (AS). However, the specific effect elicited by autophagy in endothelial cells undergoing oxidative stress remains controversial, especially during endstage autophagy. The inhibition of end-stage autophagy has been reported to increase cell pyroptosis and contribute to endothelial damage. Several studies have shown that microRNA-103 is involved in end-stage autophagy; however, its specific mechanism of action is not yet characterized. In this study, we addressed the regulatory role of miR-103 in autophagy during oxidative stress of endothelial cells. Hydrogen peroxide (H 2 O 2 ) treatment was used as an in vitro model of oxidative stress. MTS and ROS levels were measured to evaluate cell activity. qRT-PCR was used to detect the expression of miR-103. Autophagy was examined using western blot, immunofluorescence staining, and electron microscopy, while western blot analysis detected pyroptosis-related proteins. Results show that miR-103 expression decreased under oxidative stress. Further, miR-103 repressed transcription of Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3). The oxidative stress caused by H 2 O 2 caused cell damage from 2 hours (P < 0:05) and increased the level of intracellular reactive oxygen species (P < 0:05); at the same time, the damage could be further aggravated by the stimulation of bafA1 (P < 0:05). Under the stimulation of H 2 O 2 , the expression of miR-103 decreased (P < 0:05). However, high expression of miR-103 could reduce the accumulation of LC3II and P62 (P < 0:05) by inhibiting the downstream target gene Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3), thus reducing the occurrence of cell pyroptosis (P < 0:05). This process could be blocked by end-stage autophagy inhibitor bafA1 (P < 0:05), which further indicated that miR-103 affected cell injury by autophagy. On the contrary, the low expression of miR-103 promoted the accumulation of autophagy protein and increased the occurrence of pyroptosis (P < 0:05). In conclusion, inhibition of miR-103 restrained end-stage of autophagy by regulating BNIP3, thus changing the occurrence of cell pyroptosis.

Oxidative stress induces endothelial cell apoptosis and promotes atherosclerosis development. MicroRNA-210 (miR-210) is linked with apoptosis in different cell types. This study aimed to investigate the role of miR-210 in human umbilical vein endothelial cells (HUVECs) under oxidative stress and to determine the underlying mechanism. HUVECs were treated with different concentrations of hydrogen peroxide (H2O2), and cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ATP assay. To evaluate the role of miR-210 in H2O2-mediated apoptosis, gain-and-loss-of-function approaches were used, and the effects on apoptosis and reactive oxygen species (ROS) level were assayed using flow cytometry. Moreover, miR-210 expression was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and expression of the following apoptosis-related genes was assessed by qRT-PCR and Western blot at the RNA and protein level, respectively: caspase-8-associated protein 2 (CASP8AP2), caspase-8, and caspase-3. The results showed that H2O2 induced apoptosis in HUVECs in a dose-dependent manner and increased miR-210 expression. Overexpression of miR-210 inhibited apoptosis and reduced ROS level in HUVECs treated with H2O2. Furthermore, miR-210 downregulated CASP8AP2 and related downstream caspases at protein level. Thus, under oxidative stress, miR-210 has a prosurvival and antiapoptotic effect on HUVECs by reducing ROS generation and downregulating the CASP8AP2 pathway.

Background/Aims: The myocardial energy metabolism shift is one of the most important pathological features of ischemic heart disease (IHD). Although several microRNAs (miRs) are involved in the regulation of myocardial energy metabolism, their exact effects and underlying mechanisms remain unclear. The aim of this study was to investigate whether microRNA(miR-210) regulates the energy metabolism shift during oxidative stress in H9c2 cardiomyocytes. Methods: Cell survival was analyzed via CCK assay. The energy metabolism shift was detected by lactate assay, ATP assay and RT² profiler glucose metabolism PCR array. Protein and mRNA expression levels were determined by western blot and qPCR. We also used kits to detect the activity of Complex I, Sirt3 and the NAD⁺/NADH ratio. Results: We determined that miR-210 promoted the energy metabolism shift. The iron-sulfur cluster assembly protein (ISCU) was a target of miR-210. Additionally, we detected the activity of complex I and found that miR-210 inhibits mitochondrial respiration. Interestingly, miR-210 may also indirectly regulate SIRT3 by regulating ISCU. Conclusion: Our results confirm that miR-210 is essential and sufficient for modulating the cellular energy metabolism shift during H₂O₂-induced oxidative stress in H9c2 cardiomyocytes by targeting ISCU.

Ovarian cancer (OC) is one of the most common gynecological malignancies and owns the highest mortality rate among all gynecological malignant tumors. ATP binding cassette subfamily B member 9 (ABCB9) is an antigen processing-like (TAPL) transporter that has been found to be involved in the development and progression of various malignant tumors in accumulating reports. However, the potential role of ABCB9 in OC has never been reported. In this study, ABCB9 expression was evaluated in normal ovarian tissues and ovarian cancer tissues using The Cancer Genome Atlas (TCGA) database. And the associations between ABCB9 expression and clinical parameters of patients of OC were evaluated by Chi-square tests. Kaplan–Meier analysis and Cox regression analysis were performed to evaluate the prognostic significance of ABCB9. GSEA was performed to explore related signaling pathway. ABCB9 expression levels were significantly decreased in OC compared with normal ovarian tissues ( P < .001). Low ABCB9 expression was associated with survival status ( P = .0148) in OC. Kaplan–Meier analysis showed that low ABCB9 expression was associated with poor overall survival in OC ( P = .0032). Multivariable Cox regression analysis indicated that low ABCB9 expression was an independent prognostic factor (HR 0.64; P = .01) in OC patients. Besides, epithelial mesenchymal transition, UV response, and TGF-β signaling were enriched in low ABCB9 expression phenotype, respectively, examined by gene set enrichment analysis. These results suggest that ABCB9 is an independent prognostic indicator in OC with certain clinical significance.