Circ_0039960 regulates growth and Warburg effect of breast cancer cells via modulating miR-1178/PRMT7 axis.

BACKGROUND: Breast cancer (BC) is a serious threat to women's life and healthy. Increasing evidence indicated that blocking Warburg effect could attenuate the development of BC. Circular RNAs (circRNAs) has been found to be dysregulated in various carcinomas, including BC. Our study aims to illustrate the role and regulatory mechanism of circ_0039960 in BC development. METHODS: RT-qPCR and western blotting were utilized to evaluate the expression of circ_0039960 in tissues recruited from 32 cases of BC patients and also BC cell lines. Circ_0039960 shRNA was transfected into cells to explore its function on cell processes. CCK-8, flow cytometry and ELISA were used to measure cell viability, cell cycle and apoptosis. Warburg effect was detected by using commercial kits. Besides, bioinformatic prediction, RIP and luciferase reporter assays were performed to validate the interactions between circ_0039960, miR-1178 and PRMT7. RESULTS: The results showed that circ_0039960 and PRMT7 were both up-regulated, while miR-1178 was down-regulated, in BC tissues and cells. Silencing circ_0039960 effectively inhibited cell viability and Warburg effect of BC cells, also, induced cell cycle arrest and apoptosis. Moreover, we validated that circ_0039960 positively mediated PRMT7 expression via directly targeting to miR-1178. The inhibition of miR-1178 and overexpression of PRMT7 reversed the effect of circ_0039960 knockdown on BC cell growth and Warburg effect. CONCLUSION: In general, our research demonstrated that circ_0039960 regulates cell growth and Warburg effect in BC cells via miR-1178/PRMT7 axis. This may provide new evidence for the exploration of BC diagnostic and therapeutic targets.

Semisupervised Deep Stacking Network with Adaptive Learning Rate Strategy for Motor Imagery EEG Recognition.

Practical motor imagery electroencephalogram (EEG) data-based applications are limited by the waste of unlabeled samples in supervised learning and excessive time consumption in the pretraining period. A semisupervised deep stacking network with an adaptive learning rate strategy (SADSN) is proposed to solve the sample loss caused by supervised learning of EEG data and the extraction of manual features. The SADSN adopts the idea of an adaptive learning rate into a contrastive divergence (CD) algorithm to accelerate its convergence. Prior knowledge is introduced into the intermediary layer of the deep stacking network, and a restricted Boltzmann machine is trained by a semisupervised method in which the adjusting scope of the coefficient in learning rate is determined by performance analysis. Several EEG data sets are carried out to evaluate the performance of the proposed method. The results show that the recognition accuracy of SADSN is advanced with a more significant convergence rate and successfully classifies motor imagery.

Knockdown of ERO1L attenuates tumor growth, migration and invasion in lung adenocarcinoma through Wnt/ß­catenin pathway.

Recent studies confirm the critical roles of endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) in malignant behavior of various cancers. Nevertheless, what function ERO1L plays in lung adenocarcinoma (LUAD) remains uncovered. The expressions and clinical significance of ERO1L in LUAD were investigated using the TCGA dataset. The ERO1L levels were examined by RT-qPCR. The LUAD cell proliferation was valued using colony formation as well as CCK-8 assays. The invasion and migration abilities of LUAD cells were detected through Transwell in addition to wound healing assays. The effects of ERO1L on LUAD cell apoptosis were determined by flow cytometric analysis. Moreover, we also established mouse xenograft models of LUAD cells to confirm the functions of ERO1L in vivo. The ERO1L levels in tumors were identified by immunohistochemistry. Western blot was used for the detection of the levels of Wnt/ßcatenin signaling-related proteins. The TCGA database revealed that ERO1L expressions were higher in LUAD tissues than those in non-cancerous tissues. ERO1L overexpression was related to poorer overall survival of LUAD patients. In addition, ERO1L silence suppresses LUAD cell clone formation, proliferation, migration as well as invasion but induces apoptosis. Moreover, we also verified that ERO1L silence could promote LUAD growth in vivo. Based on the mechanism analysis, ERO1L was confirmed to regulate LUAD development via Wnt/ßcatenin cascade signal. ERO1L, the expression of which was increased in LUAD tissues, functioned as an oncogene. ERO1L silence significantly attenuated LUAD tumorigenesis, likely via inhibition of Wnt/ßcatenin signaling, indicating that ERO1L could be exploited as a promising biomarker in LUAD treatment.

MAPK/ERK-CBP-RFPL-3 Mediates Adipose-Derived Stem Cell-Induced Tumor Growth in Breast Cancer Cells by Activating Telomerase Reverse Transcriptase Expression.

Adipose-derived stem cells (ASCs) improve the self-renewal and survival of fat grafts in breast reconstruction after oncology surgery. However, ASCs have also been found to enhance breast cancer growth, and its role in tumor proliferation remains largely elusive. Here, we explored a novel mechanism that mediates hTERT reactivation during ASC-induced tumor growth in breast cancer cells. In this study, we found the proliferative ability of breast cancer cells markedly increased with ASC coculture. To explore the molecular mechanism, we treated cells with anibody/inhibitor and found that the activation of MEK-ERK pathway was triggered in breast cancer cells by SCF secreted from ASCs, leading to the nuclear recruitment of CBP. As a coactivator of hTERT, CBP subsequently coordinated with RFPL-3 upregulated hTERT transcription and telomerase activity. The inhibition of CBP and RFPL-3 abrogated the activation of hTERT transcription and the promotion of proliferation in breast cancer cells with cocultured ASCs in vitro and in vivo. Collectively, our study findings indicated that CBP coordination with RFPL-3 promotes ASC-induced breast cancer cell proliferation by anchoring to the hTERT promoter and upregulating telomerase activity, which is activated by the MAPK/ERK pathway.