ABSTRACT
The lncRNA NUTM2A-AS1 has been shown to be dysregulated in gastric cancer, while the roles in glioma is unclear. The aim of this study was to investigate the roles and potential mechanisms of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of glioma cells. The StarBase software and dual luciferase reporter assay were used to identify the relationship between lncRNA NUTM2A-AS1 and miR-376a-3p, and miR-376a-3p and YAP1. The expression of lncRNA NUTM2A-AS1, miR-376a-3p, and YAP1 in human glioma cell lines was detected by qRT-PCR. MTT and flow cytometry were used to detect the effects of lncRNA NUTM2A-AS1 or miR-376a-3p on the proliferation and apoptosis of U251 and A172 cells, respectively. In addition, changes of Bax and Bcl-2 expression in glioma cells were further verified by western blotting and qRT-PCR. The results showed that the expression of lncRNA NUTM2A-AS1 was elevated in glioma cell lines, while miR-376a-3p was decreased. LncRNA NUTM2A-AS1 was negatively correlated with miR-376a-3p. Silencing of lncRNA NUTM2A-AS1 enhanced the levels of miR-376a-3p, leading to reduced cell proliferation and increased apoptosis in glioma cells. YAP1 was a direct target of miR-376a-3p, and it was negatively regulated by miR-376a-3p in U251 and A172 cells. Further mechanistic studies suggested that miR-376a-3p reduced glioma cell proliferation and increased apoptosis by inhibiting YAP1 expression. In addition, lncRNA NUTM2A-AS1 positively regulated of YAP1 expression in glioma cells. In conclusion, silencing of lncRNA NUTM2A-AS1 inhibited proliferation and induced apoptosis in human glioma cells via the miR-376a-3p/YAP1 axis.
ABSTRACT
Background: Glioma is a primary malignant craniocerebral tumor commonly found in the central nervous system. According to research, preoperative diagnosis of glioma and a full understanding of its imaging features are very significant. Still, the traditional segmentation methods of image dispensation and machine wisdom are not acceptable in glioma segmentation. This analysis explores the potential of magnetic resonance imaging (MRI) brain tumor images as an effective segmentation method of glioma. Methods: This study used 200 MRI images from the affiliated hospital and applied the 2-dimensional residual block UNet (2DResUNet). Features were extracted from input images using a 2×2 kernel size (64-kernel) 1-step 2D convolution (Conv) layer. The 2DDenseUNet model implemented in this study incorporates a ResBlock mechanism within the UNet architecture, as well as a Gaussian noise layer for data augmentation at the input stage, and a pooling layer for replacing the conventional 2D convolutional layers. Finally, the performance of the proposed protocol and its effective measures in glioma segmentation were verified. Results: The outcomes of the 5-fold cross-validation evaluation show that the proposed 2DResUNet and 2DDenseUNet structure has a high sensitivity despite the slightly lower evaluation result on the Dice score. At the same time, compared with other models used in the experiment, the DM-DA-UNet model proposed in this paper was significantly improved in various indicators, increasing the reliability of the model and providing a reference and basis for the accurate formulation of clinical treatment strategies. The method used in this study showed stronger feature extraction ability than the UNet model. In addition, our findings demonstrated that using generalized die harm and prejudiced cross entropy as loss functions in the training process effectively alleviated the class imbalance of glioma data and effectively segmented glioma. Conclusions: The method based on the improved UNet network has obvious advantages in the MRI brain tumor portrait segmentation procedure. The result showed that we developed a 2D residual block UNet, which can improve the incorporation of glioma segmentation into the clinical process.
ABSTRACT
Autophagy is a cellular catabolic mechanism in response to stress conditions and has been implicated in the progression and chemoresistance of various cancers. Human microR-137 (MIR137) is involved in neuronal maturation and neurogenesis, while little is known about its role in cancer. In this study, we showed that starvation increased the formation of autophagic marker microtubule-associated protein 1 light chain 3 (LC3) without significant change of MIR137 level in U87 cells. In addition, overexpression of MIR137 decreased LC3 expression and inhibited the degradation of the autophagy receptor sequestosome 1(SQSTM1/p62), while the MIR137 antagomirs showed the opposite effect on these autophagic markers. Moreover, MIR137 overexpression decreased, while its antagomirs increased the expression of autophagy-related 7(ATG7) mRNA and protein. MIR137-mediated inhibition of autophagy was prevented by ATG7. Finally, MIR137 promoted the sensitivity of U87 cells to adriamycin, an anticancer drug. Taken together, our study demonstrated that MIR137 attenuated starvation-induced autophagy by regulating the expression of ATG7.
