LncRNA XIST regulates myocardial infarction by targeting miR-130a-3p.

The study was used to probe long noncoding RNA X-inactive specific transcript (lncRNA XIST) RNA expression profile and its influence on cell cycle, proliferation, and apoptosis in myocardial cells. We also aimed to explore the possible meditating relationship between XIST, PDE4D, and miR-130a-3p. Gene differential analysis was carried out using human lncRNA Microarray V3.0. quantitative real-time PCR was used to test mRNA expressions of XIST, miR-130a-3p, and PDE4D in normal cells and postmyocardial infarction (MI) cells. Western blot was applied to determine the protein expression profile of PED4D. Changes in viability and cell cycle/apoptosis of post-MI myocardial cells after silencing of XIST or PDE4D were investigated by MTT assay and flow cytometry, respectively. The targeting relationship between miR-130a-3p and XIST, PDE4D in myocardial cells were verified by dual luciferase reporter assay. Simulated MI environment was constructed by performing anoxic preconditioning in normal cells to probe the influence of XIST on myocardial cell apoptosis. XIST and PDE4D were overexpressed in post-MI myocardial cells, whereas miR-130a-3p was underexpressed in post-MI myocardial cells. High-expressed XIST and PDE4D both promoted myocardial cell apoptosis. High-expressed XIST also inhibited myocardial cell proliferation. XIST-downregulated miR-130a-3p and PDE4D was a direct target of miR-130a-3p. LncRNA XIST promotes MI by targeting miR-130a-3p. MI induced by PDE4D can be reversed by miR-130a-3p.

Zhou T ，Qin G ，Yang L ，Xiang D ，Li S ... -  《-》

LncRNA XIST promotes myocardial infarction by regulating FOS through targeting miR-101a-3p.

Lin B ，Xu J ，Wang F ，Wang J ，Zhao H ，Feng D ... -  《Aging-US》

lncRNA HOTAIR Protects Myocardial Infarction Rat by Sponging miR-519d-3p.

Zhang D ，Wang B ，Ma M ，Yu K ，Zhang Q ，Zhang X ... -  《-》

lncRNA GAS5 regulates myocardial infarction by targeting the miR-525-5p/CALM2 axis.

Long noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of cardiovascular diseases, especially in myocardial infarction (MI). However, the underlying molecular mechanism of how lncRNA involves and affect MI still remains unclear. This study aimed to investigate the expression of lncRNA growth arrest-specific transcript 5 (GAS5) and its effects on myocardial cells' proliferation, cell cycle, and apoptosis. The possible mechanisms involved in GAS5, calmodulin 2 (CALM2), and microRNA (miR)-525-5p were also explored. The messenger RNA (mRNA) level of CALM2, GAS5, and miR-525-5p in postmyocardial infarction (MI) and normal cells were examined by quantitative real-time polymerase chain reaction (RT-qPCR). Western blot analysis assay was conducted to detect the protein levels of CALM2. The changes of cell cycle/apoptosis and cell viability of post-MI myocardial cells (PMMC) were determined by flow cytometry analysis and MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay after knockdown of GAS5 or CALM2, respectively. Dual luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were performed to verify the targeting relationship between miR-525-5p and GAS5, CALM2 in myocardial. Hypoxic preconditioning was performed in normal cells, which constructed a simulated MI environment, and the effect of GAS5 on cardiomyocyte apoptosis was detected. Our data showed that the expression of GAS5 and CALM2 in PMMC was significantly upregulated, while the expression of miR-525-5p was downregulated. Overexpression of GAS5 and CALM2 profoundly promoted the apoptosis of myocardial cell. However, the proliferation of myocardial cell was inhibited by the upregulation of GAS5 and CALM2. Moreover, GAS5 was proved to be the target of miR-525-5p and GAS5 downregulated the expression of miR-525-5p and CALM2. In addition, lncRNA GAS5 promotes MI, while CALM2 induced MI can be reversed by miR-525-5p. These data suggested that lncRNA GAS5 promoted the development and progression of MI via targeting of the miR-525-5p/CALM2 axis and it has the potential to be explored as a therapeutic target for the treatment of MI in the future.

Zhang Y ，Hou YM ，Gao F ，Xiao JW ，Li CC ，Tang Y ... -  《-》

circ_0023461 Silencing Protects Cardiomyocytes from Hypoxia-Induced Dysfunction through Targeting miR-370-3p/PDE4D Signaling.

Acute myocardial infarction (AMI) is a common cardiovascular disease with high disability and mortality. Circular RNAs (circRNAs) are implicated in the pathomechanism of multiple human diseases, including AMI. This study intended to explore the function and working mechanism of a novel circRNA circ_0023461 in hypoxia-induced cardiomyocytes. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were implemented to detect RNA and protein expression. Cell counting kit-8 (CCK8) assay and 5-ethynyl-2'-deoxyuridine (Edu) assay were conducted to analyze cell viability and proliferation ability. Cell migration and apoptosis were assessed by Transwell assay and flow cytometry. Cell oxidative stress was analyzed using the commercial kits. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze cell inflammation. Cell glycolytic metabolism was evaluated using the commercial kits. Dual-luciferase reporter assay and RNA pull-down assay were conducted to verify the intermolecular interactions. circ_0023461 expression was upregulated in AMI patients and hypoxia-induced AC16 cells. Hypoxia restrained the viability, proliferation, migration, and glycolysis and induced the apoptosis, oxidative stress, and inflammation of AC16 cells, and these effects were attenuated by the silence of circ_0023461. MicroRNA-370-3p (miR-370-3p) was verified as a target of circ_0023461, and circ_0023461 silencing-mediated protective effects in hypoxia-induced cardiomyocytes were partly alleviated by the knockdown of miR-370-3p. miR-370-3p interacted with the 3' untranslated region (3' UTR) of phosphodiesterase 4D (PDE4D), and PDE4D overexpression partly reversed miR-370-3p overexpression-induced protective effects in hypoxia-induced cardiomyocytes. circ_0023461 can upregulate PDE4D expression by acting as a molecular sponge for miR-370-3p in AC16 cells. circ_0023461 knockdown attenuated hypoxia-induced dysfunction in AC16 cells partly by targeting the miR-370-3p/PDE4D axis.

Ren K ，Li B ，Jiang L ，Liu Z ，Wu F ，Zhang Y ，Liu J ，Duan W ... -  《-》