Dataset Information

LncRNA H19 Alleviated Myocardial I/RI via Suppressing miR-877-3p/Bcl-2-Mediated Mitochondrial Apoptosis.

ABSTRACT: Ischemic cardiac disease is the leading cause of morbidity and mortality in the world. Despite the great efforts and progress in cardiac research, the current treatment of cardiac ischemia reperfusion injury (I/RI) is still far from being satisfactory. This study was performed to investigate the role of long non-coding RNA (lncRNA) H19 in regulating myocardial I/RI. We found that H19 expression was downregulated in the I/R hearts of mice and cardiomyocytes treated with H2O2. Overexpression of H19 alleviated myocardial I/RI of mice and cardiomyocyte injury induced by H2O2. We found that H19 functioned as a competing endogenous RNA of miR-877-3p, which decreased the expression of miR-877-3p through the base-pairing mechanism. In parallel, miR-877-3p was upregulated in H2O2-treated cardiomyocytes and mouse ischemia reperfusion (I/R) hearts. miR-877-3p exacerbated myocardial I/RI and cardiomyocyte apoptosis. We further established Bcl-2 as a downstream target of miR-877-3p. miR-877-3p inhibited the mRNA and protein expression of Bcl-2. Furthermore, H19 decreased the Bcl-2/Bax ratio at mRNA and protein levels, cytochrome c release, and activation of caspase-9 and caspase-3 in myocardial I/RI mice, which were canceled by miR-877-3p. In summary, the H19/miR-877-3p/Bcl-2 pathway is involved in regulation of mitochondrial apoptosis during myocardial I/RI, which provided new insight into molecular mechanisms underlying regulation of myocardial I/RI.

SUBMITTER: Li X

PROVIDER: S-EPMC6612907 | biostudies-other | 2019 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

lncRNA H19 Alleviated Myocardial I/RI via Suppressing miR-877-3p/Bcl-2-Mediated Mitochondrial Apoptosis.

Li Xin X Luo Shenjian S Zhang Jifan J Yuan Yin Y Jiang Wenmei W Zhu Haixia H Ding Xin X Zhan Linfeng L Wu Hao H Xie Yilin Y Song Rui R Pan Zhenwei Z Lu Yanjie Y

Molecular therapy. Nucleic acids 20190614

Ischemic cardiac disease is the leading cause of morbidity and mortality in the world. Despite the great efforts and progress in cardiac research, the current treatment of cardiac ischemia reperfusion injury (I/RI) is still far from being satisfactory. This study was performed to investigate the role of long non-coding RNA (lncRNA) H19 in regulating myocardial I/RI. We found that H19 expression was downregulated in the I/R hearts of mice and cardiomyocytes treated with H<sub>2</sub>O<sub>2</sub> ...[more]

PMID: 31284127

Similar Datasets

Project description:The current investigation explored the synthetic contribution of lncRNA H19, miR-130a-3p, and miR-17-5p to radio-resistance and chemo-sensitivity of cardiac cancer cells. Totally 284 human cardiac cancer tissues were gathered, and they have been pathologically diagnosed. The cardiac cancer cells were isolated with utilization of the mechanic method. Moreover, cisplatin, adriamycin, mitomycin, and 5-fluorouracil were designated as the chemotherapies, and single-dose X-rays were managed as the radiotherapy for cardiac cancer cells. We also performed luciferase reporter gene assay to verify the targeted relationship between H19 and miR-130a-3p, as well as between H19 and miR-17-5p. Finally, mice models were established to examine the functions of H19, miR-130a-3p, and miR-17-5p on the development of cardiac cancer. The study results indicated that H19, miR-130a-3p, and miR-17-5p expressions within cardiac cancer tissues were significantly beyond those within adjacent nontumor tissues (P < 0.05), and H19 expression was positively correlated with both miR-130a-3p (rs = 0.43) and miR-17-5p (rs = 0.49) expressions. The half maximal inhibitory concentrations (IC50) of cisplatin, adriamycin, mitomycin, and 5-fluorouracil for cardiac cancer cells were, respectively, determined as 2.01 μg/mL, 8.35 μg/mL, 24.44 μg/mL, and 166.42 μg/mL. The overexpressed H19, miR-130a-3p, and miR-17-5p appeared to improve the survival rate and viability of cardiac cancer cells that were exposed to chemotherapies and X-rays (all P < 0.05). It was also drawn from luciferase reporter gene assay that H19 could directly target miR-130a-3p and miR-17-5p, thereby modifying the sensitivity of cardiac cancer cells to drugs and X-rays (P < 0.05). Finally, the mice models also produced larger tumor size and higher tumor weight, when H19, miR-130a-3p, or miR-17-5p expressions were up-regulated within them (P < 0.05). In conclusion, H19 could act on miR-130a-3p or miR-17-5p to alter the radio- and chemo-sensitivities of cardiac cancer cells, helping to improve the radio-/chemotherapies for cardiac cancer.

Dataset Information

LncRNA H19 Alleviated Myocardial I/RI via Suppressing miR-877-3p/Bcl-2-Mediated Mitochondrial Apoptosis.

Publications

lncRNA H19 Alleviated Myocardial I/RI via Suppressing miR-877-3p/Bcl-2-Mediated Mitochondrial Apoptosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets