Myocarditis is an inflammatory disease of the myocardium. MicroRNA‐203 (miR‐203) is involved in various physiological and pathological processes. In this work, we aimed to explore the roles and potential mechanisms of miR‐203 in myocarditis in vitro. Cardiomyocyte H9c2 was subjected to 10 μg/mL lipopolysaccharide (LPS) for 24 hours. Real‐time polymerase chain reaction analysis revealed that LPS upregulated miR‐203 expression in H9c2 cells. Cell counting kit‐8 (CCK‐8) and lactate dehydrogenase (LDH) assays demonstrated that inhibition of miR‐203 reduced cell injury induced by LPS. The cell apoptosis rate, caspase 3 activity, caspase 3/7 activities, and the expression of cleaved‐caspase 3 (c‐caspase 3) were declined upon miR‐203 depletion. In addition, miR‐203 silencing attenuated the expression and production of inflammatory cytokines (tumor necrosis factor‐α, interleukin [IL]‐6, and IL‐8). On the contrary, overexpression of miR‐203 showed the opposite trend in cell apoptosis and inflammation. Luciferase reporter assay confirmed that miR‐203 could bind with the nuclear factor interleukin‐3 (NFIL3) 3′‐untranslated regions (3′‐UTR), and miR‐203 regulated the expression of NFIL3 negatively. Moreover, NFIL3 silencing partly abolished the myocardial protective functions of miR‐203 inhibitor. Herein, we suggest that miR‐203 promoted cell apoptosis and inflammation induced by LPS via targeting NFIL3.

N-myc downstream regulated gene 1 (NDRG1) plays a variety of roles in human cancers. Our previous studies showed that NDRG1 expression is elevated in non-small cell lung cancer and contributes to cancer growth. However, its function in apoptosis and chemoresistance in malignant tumors, including lung cancer, is not yet fully understood. In this study, we investigated the roles of NDRG1 in chemoresistance to cisplatin in lung cancer cells. We found that overexpression of NDRG1 significantly reduced cisplatin-induced cytotoxicity in lung cancer A549 cells, while overexpression of activating transcription factor 3 (ATF3), a stress-inducible gene found to be associated with apoptosis in some human cancers, significantly promoted cytotoxicity (P < 0.05). Further investigation showed that overexpression of NDRG1 significantly downregulated ATF3 and P53 expression in A549 cells, while overexpression of ATF3 significantly upregulated P53 expression (P < 0.05). In addition, cisplatin significantly upregulated ATF3, phospho-P53(ser46), and cleaved caspase 3 expression in lung cancer cells, but overexpression of NDRG1 in the presence of cisplatin reduced the level of these proteins elevated by cisplatin (P < 0.05). While, overexpression of ATF3 significantly promoted the cytoxicity induced by cisplatin in 1299 cells (p<0.05) (Figure 4), but overexpression of NDRG1 didn't regulate the cytoxicity induced by cisplatin (p>0.05). These results indicate that NDRG1 may contribute to cisplatin-resistance in lung cancer, possibly due to its function in the regulation of ATF3 expression.

Thymosin β‐4 (Tβ4) is a ubiquitous protein, which has been suggested to regulate multiple cell signal pathways and a variety of cellular functions. However, the role Tβ4 plays in the cardiac microvascular endothelial cells (CMECs) under myocardial ischemia/reperfusion injury is currently unknown. Here we investigated the effects of Tβ4 on hypoxia/reoxygenation (H/R) induced CMECs injury and its potential molecular mechanism. Cultured CMECs were positively identified by flow cytometry using antibody against CD31 and VWF/Factor VIII, which are constitutively expressed on the surface of CMECs. Then the reduced level of Tβ4 was detected in H/R‐CMECs by a real‐time quantitative polymerase chain reaction. To determine the effects of Tβ4 on H/R‐CMECs, we transfected the overexpression or silence vector of Tβ4 into CMECs under H/R condition. Our results indicated that H/R treatment could reduce proliferation, increased apoptosis, adhesion, and reactive oxygen species (ROS) production in CMECs, which were attenuated by Tβ4 overexpression or aggravated by Tβ4 silencing, implying Tβ4 is able to promote CMECs against H/R‐induced cell injury. Furthermore, the microRNA‐200a (miR‐200a) level was also increased by Tβ4 in H/R‐CMECs or reduced by Tβ4 small interfering RNA. To investigated the mechanism of protective effects of Tβ4 on CMECs injury, the miR‐200a inhibitor was transfected into H/R‐CMECs. The results indicated that inhibition of miR‐200a inversed the protection of Tβ4 on H/R‐CMECs, specifically including cell proliferation, cell adhesion, cell apoptosis, and ROS production, as well as nuclear factor erythroid 2‐related factor 2 (Nrf2) nuclear translocation. In conclusion, our results determined that Tβ4 attenuated H/R‐induced CMECs injury by miR‐200a‐Nrf2 signaling.