Exosomal LINC00174 derived from vascular endothelial cells attenuates myocardial I/R injury via p53-mediated autophagy and apoptosis

Su, Qiang; Lv, Xiangwei; Xu, Yu; Cai, Ruping; Dai, Rixin; Yang, Xiheng; Zhao, Weikun; Kong, Biao

doi:10.1016/j.omtn.2021.02.005

Cited by 34 publications

(32 citation statements)

References 65 publications

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“…Overexpression of LINC00174 promotes the proliferation, migration, and invasion of colorectal cancer cells by regulating Mir-1910-3p/TAZ and Mir-3127-5p/E2F7 signaling pathways (44,45). LINC00174, as an autophagyrelated lncRNA, secreted by vascular endothelial cells, inhibits autophagy by SRSF1/P53 signaling pathway, which can alleviate myocardial insulin-reperfusion injury (46). In addition, NKILA can enhance autophagy of HK2 cells through Mir-140-5p/ CLDN2/LPS pathway to induce acute kidney injury (47).…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs

Yang

Wang

et al. 2021

Front. Oncol.

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IntroductionColorectal cancer (CRC) is the most common gastrointestinal cancer and has a low overall survival rate. Tumor–node–metastasis staging alone is insufficient to predict patient prognosis. Autophagy and long noncoding RNAs play important roles in regulating the biological behavior of CRC. Therefore, establishing an autophagy-related lncRNA (ARlncRNA)-based bioinformatics model is important for predicting survival and facilitating clinical treatment.MethodsCRC data were retrieved from The Cancer Genome Atlas. The database was randomly divided into train set and validation set; then, univariate and multivariate Cox regression analyses were performed to screen prognosis-related ARlncRNAs for prediction model construction. Interactive network and Sankey diagrams of ARlncRNAs and messenger RNAs were plotted. We analyzed the survival rate of high- and low-risk patients and plotted survival curves and determined whether the risk score was an independent predictor of CRC. Receiver operating characteristic curves were used to evaluate model sensitivity and specificity. Then, the expression level of lncRNA was detected by quantitative real-time polymerase chain reaction, and the location of lncRNA was observed by fluorescence in situ hybridization. Additionally, the protein expression was detected by Western blot.ResultsA prognostic prediction model of CRC was built based on nine ARlncRNAs (NKILA, LINC00174, AC008760.1, LINC02041, PCAT6, AC156455.1, LINC01503, LINC00957, and CD27-AS1). The 5-year overall survival rate was significantly lower in the high-risk group than in the low-risk group among train set, validation set, and all patients (all p < 0.001). The model had high sensitivity and accuracy in predicting the 1-year overall survival rate (area under the curve = 0.717). The prediction model risk score was an independent predictor of CRC. LINC00174 and NKILA were expressed in the nucleus and cytoplasm of normal colonic epithelial cell line NCM460 and colorectal cancer cell lines HT29. Additionally, LINC00174 and NKILA were overexpressed in HT29 compared with NCM460. After autophagy activation, LINCC00174 expression was significantly downregulated both in NCM460 and HT29, while NKILA expression was significantly increased.ConclusionThe new ARlncRNA-based model predicts CRC patient prognosis and provides new research ideas regarding potential mechanisms regulating the biological behavior of CRC. ARlncRNAs may play important roles in personalized cancer treatment.

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Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs

Yang

Wang

et al. 2021

Front. Oncol.

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“…Therefore, it is necessary to find an effective molecular mechanism to improve myocardial cell apoptosis after ischaemia-reperfusion. The current study shows that lncRNAs are important molecules that regulate I/R in vascular organs ( Zeng et al, 2019 ; Hu et al, 2020 ; Su et al, 2021 ). Knockdown of lncRNA AK139328 can reduce myocardial ischemia/reperfusion injury in diabetic mice ( Yu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 75%

The Novel LncRNA AK035396 Drives Cardiomyocyte Apoptosis Through Mterf1 in Myocardial Ischemia/Reperfusion Injury

Hong

et al. 2021

Front. Cell Dev. Biol.

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Background: Myocardial ischaemia/reperfusion (I/R) injury is still a major challenge in clinical treatment. The role of long non-coding RNA (lncRNA) in the regulation of myocardial I/R injury still needs to be elucidated.Methods: The primary isolated neonatal mousse cardiomyocytes and adult mice were used to construct a myocardial ischemia-reperfusion model. qRT-PCR is used to verify gene expression in myocardial tissue and myocardial cells. The effect of AK035396 in primary cardiomyocytes and mouse myocardium was confirmed by TUNEL staining and in vitro flow cytometry experiments. RNA pulldown and Western blot were used to identify AK035396 interacting proteins. The expression of apoptosis-related proteins was identified by qRT-PCR and Western blot.Results:In vivo and in vitro MIRI models, AK035396 was up-regulated after myocardial infarction. Functional studies have shown that knockdown of AK035396 reduces the apoptosis of primary cardiomyocytes and mouse myocardial tissue. AK035396 directly interacts with Mterf1 and inhibits the level of Mterf1. Further experiments have shown that inhibiting Mterf1 will promote the expression of mitochondrial genes COXII and CYTb and cause cell apoptosis.Conclusion: AK035396 plays an important role in myocardial ischaemia-reperfusion injury by regulating the Mterf1-COXII/CYTb pathway.

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“…9 By contrast, the apoptosis rates of VSMCs did not significantly change after 5 0 -tiRNA-Cys-GCA overexpression (Figure 2H), which was further confirmed by detecting the expression levels of apoptosis-related proteins, p53 and cleaved caspase-3 (c-caspase-3; Figure 2G). 44,45 In summary, 5 0 -tiRNA-Cys-GCA mainly regulated VSMC proliferation, migration, and phenotype transition and did not significantly affect the apoptosis of VSMCs. The regulatory effect of 5 0 -tiRNA-Cys-GCA on the proliferation, migration, and phenotypic transition of VSMCs was further verified by knockdown of 5 0 -tiRNA-Cys-GCA.…”

Section: Resultsmentioning

confidence: 88%

5′-tiRNA-Cys-GCA regulates VSMC proliferation and phenotypic transition by targeting STAT4 in aortic dissection

Zong

Yang

Lin

et al. 2021

Molecular Therapy - Nucleic Acids

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Accumulating evidence shows that tRNA-derived fragments are a novel class of functional small non-coding RNA; however, their roles in aortic dissection (AD) are still unknown. In this study, we found that 5 0 -tiRNA-Cys-GCA was significantly downregulated in human and mouse models of aortic dissection. The abnormal proliferation, migration, and phenotypic transition of vascular smooth muscle cells (VSMCs) played a crucial role in the initiation and progression of aortic dissection, with 5 0 -tiRNA-Cys-GCA as a potential phenotypic switching regulator, because its overexpression inhibited the proliferation and migration of VSMCs and increased the expression of contractile markers. In addition, we verified that signal transducer and activator of transcription 4 (STAT4) was a direct downstream target of 5 0 -tiRNA-Cys-GCA. We found that the STAT4 upregulation in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs, which promoted cell proliferation, migration, and phenotypic transformation, was reversed by 5 0 -tiRNA-Cys-GCA. Furthermore, 5 0 -tiRNA-Cys-GCA treatment reduced the incidence and prevented the malignant process of angiotensin II-and b-aminopropionitrile-induced AD in mice. In conclusion, our findings reveal that 5 0 -tiRNA-Cys-GCA is a potential regulator of the AD pathological process via the STAT4 signaling pathway, providing a novel clinical target for the development of future treatment strategies for aortic dissection.

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Exosomal LINC00174 derived from vascular endothelial cells attenuates myocardial I/R injury via p53-mediated autophagy and apoptosis

Cited by 34 publications

References 65 publications

A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs

A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs

The Novel LncRNA AK035396 Drives Cardiomyocyte Apoptosis Through Mterf1 in Myocardial Ischemia/Reperfusion Injury

5′-tiRNA-Cys-GCA regulates VSMC proliferation and phenotypic transition by targeting STAT4 in aortic dissection

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