Distant metastasis is the major contributor to the high mortality rate of colorectal cancer (CRC). To overcome the poor prognosis caused by distant metastasis, the mechanisms of CRC metastasis should be further explored. Epigenetic events are the main mediators of gene regulation and further affect tumor progression. Recent studies have found that some epigenetic enzymes are often dysregulated or mutated in multiple tumor types, which prompted us to study the roles of these enzymes in CRC metastasis. In this review, we summarized the alteration of enzymes related to various modifications, including histone modification, nonhistone modification, DNA methylation, and RNA methylation, and their epigenetic mechanisms during the progression of CRC metastasis. Existing data suggest that targeting epigenetic enzymes is a promising strategy for the treatment of CRC metastasis.
The roles of gap junctions (GJs) and its components, connexins, in the autophagy of cervical cancer cells have been rarely investigated. Our previous study demonstrated that connexin 32 (Cx32) exerted an anti-apoptotic effect on cervical cancer. However, as an important regulator of apoptosis, whether the autophagy is involved in the function of Cx32 on cervical cancer cells is not well defined. The present study aimed to investigate the role of Cx32 on autophagy and apoptosis inhibition in cervical cancer cells. The expression levels of Cx32 and the autophagy-associated protein LC3-Ⅱ in paracancerous cervical tissues (n=30) and cervical cancer (n=50) tissues were determined via western blotting. In total, 45 cervical cancer specimens were used to evaluate the clinical relevance of Cx32 and LC3-Ⅱ. It was found that both Cx32 and LC3-Ⅱ were upregulated in cervical cancer tissues compared with those in paracancerous cervical tissues. The effect of Cx32 on autophagy was examined by detecting the change of LC3-Ⅱ using western blotting, transfection with enhanced green fluorescent protein-LC3 plasmid and transmission electron microscopy analysis. Overexpression of Cx32 significantly enhanced autophagy in HeLa-Cx32 cells, whereas knockdown of Cx32 suppressed autophagy in C-33A cells. The flow cytometry results demonstrated that Cx32 inhibited the apoptosis of cervical cancer cells by promoting autophagy. Moreover, Cx32 triggered autophagy via the activation of the AMP-activated protein kinase (AMPK) signalling, regardless of the presence or absence of GJs. Collectively, it was identified that Cx32 exerted its anti-apoptotic effect by activating autophagy via the AMPK pathway in cervical cancer, which demonstrates a novel mechanism for Cx32 in human cervical cancer progression.
Organic electrochemical metallization (ECM) memory that possesses high reliable switching performance is in great demand for the future smart wearable and flexible electronics. The resistive switching (RS) behavior of organic ECM memory is determined by the micro‐morphology evolution of metal conductive filaments (CFs) during the operating process. However, the morphology controllability of CFs is generally deteriorated by their random distribution and unexpected overgrowth. Herein, a kind of nanoporous PVC/TiO2 nanocomposite is developed using photocatalytic method for improving the RS reliability of organic ECM memory. The introduction of engineered nanopores can effectively simplify the CFs morphology to obtain excellent uniformity, good retention, and low cycling degradation. In addition, taking advantage of the multilevel RS behavior and 200 × 200 memristive array artificial neural network (ANN), alphabetic data storage and image pattern recognition are successfully realized. The proposed approach is expected to provide novel platforms for the advance of highly reliable flexible electronics and ANN for intelligence applications.
Background: Oxaliplatin (L-OHP) and 5-fluorouracil (5-FU) resistance in colorectal cancer (CRC) is a major medical problem. Therefore, detailed mechanisms and predictive markers are urgently needed. The aim of this study was to identify key pathways, a robust prognostic gene signature and potential drug-repurposing. Methods: In order to confirm the predictive markers and detailed molecular mechanisms of L-OHP and 5-Fu chemoresistant CRC, we performed weighted correlation network analysis (WGCNA), an unsupervised analysis method, to identify the chemoresistant CRC significantly related genes. Then, the gene prognostic model was conducted by Univariate Cox regression and Lasso penalized Cox regression analysis. Subsequently, the time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curve were performed to assess the prognostic capacity of the model. Simultaneously, pathway enrichment was done to identify the key pathways involved in chemoresistant CRC. Moreover, we explored how the hub genes interacted with key pathways and transcription factors. Then, we found the potential drug target by the subcellular location fo hub genes. Finally, we identified the potential drug-repurposing by virtual screening for chemoresistant CRC according to ZINC 15 database. Results: We identified the key pathways using KEGG over-representation test and Gene Set Enrichment Analysis (GSEA): Ribosome KEGG pathway. Moreover, six hub-genes prognostic model was conducted by Univariate Cox regression and Lasso penalized Cox regression analysis. Additionally, the detailed interactions among the pathway and hub genes (RBM6, PNN, LEF1, ANO1, PAFAH1B3 and BHLHE41) were examined by protein-protein interaction (PPI) network and shortest-pathway analysis. Furthermore, ANO1 was considered the potential drug target based on the subcellular location and ZINC000018043251 was verified the potential drug by virtual screening Conclusions: Our study identified a novel six-gene resistant signature for CRC prognosis prediction and the molecular details of these interactions between hub genes (RBM6, PNN, LEF1, ANO1, PAFAH1B3 and BHLHE41) and Ribosome key pathways. Furthermore, ZINC000018043251 was verified the potential drug for ANO1 by virtual screening, which might help to improve the outcome of CRC patients.
BackgroundThe roles of gap junction and its components, connexins in autophagy of cervical cancer cells are rarely investigated. Our previous study demonstrated that connexin32 (Cx32) exerted an anti-apoptotic effect on cervical cancer (CaCx). However, as an important regulator of apoptosis, whether the autophagy is involved in the function of Cx32 on cervical cancer cells are not well defined.MethodsThe expression of Connexin32 and the autophagy-associated protein LC3-Ⅱ in paracancerous cervical tissues (n = 30) and cervical cancer (n = 50) tissues were determined by Western blotting. Forty-five cervical cancer specimens were used to evaluate the clinical relevance of Connexin32 and LC3-Ⅱ. The effect of Connexin32 on autophagy was examined by detecting the change of LC3-Ⅱ using Western blotting, transfection with enhanced green fluorescent protein-LC3 plasmid and transmission electron microscopy analysis. The mechanism of Connexin32-mediated autophagy was assessed by Western blotting and flow cytometry.ResultsBoth Connexin32 and LC3-Ⅱ are upregulated in cervical cancer tissues compared to those in paracancerous cervical tissues. Overexpression of Connexin32 significantly enhanced autophagy in HeLa-Connexin32 cells, whereas knockdown of Connexin32 suppressed autophagy in C-33A cells. Connexin32 inhibited apoptosis of cervical cancer cells by promoting autophagy. Moreover, Connexin32 triggered autophagy by activation of the AMP-activated protein kinase signalling, which was gap junction-independent.ConclusionConnexin32 exerts its anti-apoptotic effect by activating autophagy through the AMPK pathway in cervical cancer. This finding suggests that Connexin32 is a potential biomarker and a new therapeutic target for cervical cancer.Trial registrationThe study was approved by the Research Committee of Ethics of the Affiliated Cancer Hospital of Xinjiang Medical University (K-201354).
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