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Aberrant expression of microRNAs hae been shown to be closely associated with glioblastoma cell proliferation, apoptosis and drug resistance. However, mechanisms underlying the role of mcroRNAs in glioblastoma cell growth and apoptosis are not fully understood. In this study, we report that miR-503 is overexpressed in glioblastoma tissue compared with normal human brain tissue. Mechanistically, miR-503 can be induced by TGF-â1 at the transcriptional level by binding the smad2/3 binding elements in the promoter. Ectopic overexpression of miR-503 promotes cell growth and inhibits apoptosis by targeting PDCD4. In contrast, inhibition of miR-503 reduces cell growth. Furthermore, miR-503 inhibitor augments the growth inhibitory effect of temozolomide in glioblastoma cells. These results establish miR-503 as a promising molecular target for glioblastoma therapy.

Doxorubicin (Dox) is an effective chemotherapeutic drug for the treatment of various cancers. Due to its potential fatal cardiotoxic side effects, the clinical application is often limited. Dexrazoxane (Dex) is the only drug approved by the Food and Drug Administration (FDA) for the prevention of Dox-induced cardiotoxicity but has side effects. Thus, more protective strategies should be explored. If NAD+ plays a role in maintaining heart function, its precursor prospectively alleviates Dox-induced cellular injury. Here, we studied the protective effects of nicotinic acid riboside (NAR) on Dox-induced cardiotoxicity in vivo and in vitro. We found that NAR significantly improved the cardiac function of Dox-treated mice by restoring ejection fraction (EF), fractional shortening (FS), and serum level of cardiac troponin (cTnI). NAR not only reduced malondialdehyde (MDA), lactate dehydrogenase (LDH), and reactive oxygen species (ROS) levels in Dox-treated cardiomyocytes but also further promoted the activities of cardiac superoxide dismutase (SOD) and glutathione (GSH). Following exposure to 5 μM Dox, cotreatment with NAR exhibited increased cell viability with a decrease in the apoptosis cell population. Moreover, the levels of apoptosis-related proteins, as well as proteins involved in oxidative stress and autophagy, were altered after NAR treatment. Collectively, these findings underline the protective potential of NAR against Dox-induced cardiomyocyte injury by regulating Nrf-2/P62-related oxidative stress and autophagy, which could potentially promote survival. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNA) growth arrest‐specific 5 (GAS5) is implicated in several cancers via modulating microRNAs (miRs). However, little information is available about the correlation between GAS5 and miR‐10b. Therefore, we sought out to investigate the biological role of GAS5‐miR‐10b node mainly in glioma cells. We artificially modulated GAS5 to explore its roles in viability assayed by cell counting kit‐8 (CCK‐8), motile activities by 24‐Transwell assay, as well as apoptosis by a flow cytometer and Western blot assay. miR‐10b and Sirtuin 1 (Sirt1) were quantified by qRT‐PCR. After co‐transfection, we analyzed the viability, migration, invasion, apoptosis, and Sirt1 expression. Western blot was implemented to detect the phosphorylated forms of PTEN, PI3K, AKT, MEK, and ERK. GAS5 inhibited proliferation and motile behaviors, and fortified apoptosis. As for the viability and motile activities, the property of GAS5 was reversed in miR‐10b‐replenished U251 and A172 cells, while maintained in miR‐10b‐deficient cells. Additionally, GAS5‐induced apoptosis was abolished by miR‐10b overexpression while fortified by miR‐10b silence. Besides, GAS5 negatively modulated Sirt1 via miR‐10b. Moreover, Sirt1 negatively modulated PTEN and positively mediated the abovementioned regulators. GAS5 represses the process of glioma cells by decreasing miR‐10b, which as accompanied by Sirt1 silence‐induced inactivation of PTEN/PI3K/AKT and MEK/ERK cascades. [ABSTRACT FROM AUTHOR]