Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.

/pdf/noncoding-rnas-in-gastric-cancer-implications-for-drug-3w5e7wjv27.pdf

Noncoding RNAs in gastric cancer: implications for drug resistance

Non-coding RNAs (ncRNAs) have been implicated in most cellular functions The disruption of their function through somatic mutations, genomic imprinting, transcriptional and post-transcriptional regulation, plays an ever-increasing role in cancer development ncRNAs, including notorious microRNAs, have been thus proposed to function as tumor suppressors or oncogenes, often in a context-dependent fashion In parallel, ncRNAs with altered expression in cancer have been reported to exert a key role in determining drug sensitivity or restoring drug responsiveness in resistant cells Acquisition of resistance to anti-cancer drugs is a major hindrance to effective chemotherapy and is one of the most important causes of relapse and mortality in cancer patients For these reasons, non-coding RNAs have become recent focuses as prognostic agents and modifiers of chemo-sensitivity This review starts with a brief outline of the role of most studied non-coding RNAs in cancer and then highlights the modulation of cancer drug resistance via known ncRNAs based mechanisms We identified from literature 388 ncRNA-drugs interactions and analyzed them using an unsupervised approach Essentially, we performed a network analysis of the non-coding RNAs with direct relations with cancer drugs Within such a machine-learning framework we detected the most representative ncRNAs-drug associations and groups We finally discussed the higher integration of the drug-ncRNA clusters with the goal of disentangling effectors from downstream effects and further clarify the involvement of ncRNAs in the cellular mechanisms underlying resistance to cancer treatments

The Network of Non-coding RNAs in Cancer Drug Resistance.

For the past several decades, significant efforts have been devoted to modeling and analysis of rolling-element bearings to aid in their design and application. This paper reviewed the modeling and analysis of rolling-element bearings with emphasis on single-row ball and roller bearings. The application of bearing models was reviewed as well along with illustrative results.

Rolling-element bearing modeling: A review

Zinc finger E-box binding homeobox 2 (ZEB2) is a DNA-binding transcription factor, which is mainly involved in epithelial-to-mesenchymal transition (EMT). EMT is a conserved process during which mature and adherent epithelial-like state is converted into a mobile mesenchymal state. Emerging data indicate that ZEB2 plays a pivotal role in EMT-induced processes such as development, differentiation, and malignant mechanisms, for example, drug resistance, cancer stem cell-like traits, apoptosis, survival, cell cycle arrest, tumor recurrence, and metastasis. In this regard, the understanding of mentioned subjects in the development of normal and cancerous cells could be helpful in cancer complexity of diagnosis and therapy. In this study, we review recent findings about the biological properties of ZEB2 in healthy and cancerous states to find new approaches for cancer treatment.

The crucial role of ZEB2: From development to epithelial-to-mesenchymal transition and cancer complexity.

Gastric cancer is the fifth most common malignancy in the world, with Eastern Asia as one of areas with the highest incidence rates. Trastuzumab, a HER2-targeting antibody, combined with chemotherapy has been successfully employed for the gastric cancer patients with HER2 overexpression/amplification. However, trastuzumab resistance is a major problem in clinical practice. Here we observed that the trastuzumab-resistant gastric cancer cell line NCI-N87/TR expressed high levels of epithelial-mesenchymal transition factors and demonstrated increased migration and invasion capability compared with NCI-N87 cells. Downregulated E-cadherin and increased N-cadherin, TGF-β, ZEB1, ZEB2, TWIST1, and Snail were detected in NCI-N87/TR cells. We also found that miR-200c was downregulated in NCI-N87/TR cells compared with parental cells NCI-87 by qRT-PCR. Treatment with TGF-β downregulated the expression of miR-200c and upregulated ZEB2, and significantly decreased the trastuzumab sensitivity of NCI-N87 cells. miR-200c restored trastuzumab sensitivity and inhibited migration and invasion through suppressing ZEB1 and ZEB2. In summary, TGF-β/ZEB2 axis plays an encouraging role in trastuzumab resistance of gastric cancer, while miR-200c overexpression downregulates ZEB1/ZEB2 and resensitizes drugs resistance. Our findings might provide a potential therapeutic strategy for trastuzumab resistance of gastric cancer.

miR-200c inhibits TGF-β-induced-EMT to restore trastuzumab sensitivity by targeting ZEB1 and ZEB2 in gastric cancer.

This study was specifically designed to confirm the hypothesis that microRNA-200c (miR-200c) affects the development of cisplatin (DDP) resistance in human gastric cancer cells by targeting zinc finger E-box binding homeobox 2 (ZEB2) A total of 50 gastric cancer tissues and their corresponding normal adjacent tissue samples were collected Then, the expression levels of miR-200c and ZEB2 in both gastric cancer specimens and cells were detected using the quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical methods A dual‑luciferase reporter gene assay was conducted to evaluate the effect of miR-200c on the 3'-untranslated region (3'UTR) luciferase activity of ZEB2 SGC7901/DDP cells were transfected with miR-200c mimics and ZEB2 siRNA, respectively Subsequently, changes in cellular proliferation and apoptosis were detected through the methyl thiazolyl tetrazolium assay and flow cytometric analysis, respectively We also carried out a western blot analysis assay in order to detect the expression of apoptosis-related genes and ZEB2 miR-200c was significantly downregulated and ZEB2 was significantly upregulated in both gastric cancer tissues and SGC7901/DDP cells when compared with those in normal tissues and SGC7901 cells (P<001) The dual luciferase reporter gene assay showed that miR-200c could specifically bind with the 3'UTR of ZEB2 and significantly suppress the luciferase activity by 42% (P<001) Upregulation of miR-200c or downregulation of ZEB2 enhanced the sensitivity of SGC7901/DDP cells to DDP miR‑200c was significantly downregulated in both gastric cancer tissues and cells, while the expression of ZEB2 exhibited the opposite trend Our study further demonstrated that miR-200c could enhance the sensitivity of SGC7901/DDP cells to DDP through targeted regulation of ZEB2 expression in gastric cancer tissues

/pdf/microrna-200c-regulates-cisplatin-resistance-by-targeting-49tjpjw8jb.pdf

MicroRNA-200c regulates cisplatin resistance by targeting ZEB2 in human gastric cancer cells.

The elastohydrodynamic traction coefficients of two Chinese aviation lubricating oils were investigated for various loads, rolling velocities, and lubricant inlet temperatures using a self-made test rig. Traction coefficient versus slide-to-roll ratio curves were generated. The concept of critical load varying with the lubricant temperature is proposed. This paper presents a new empirical formula for the dynamic performance design of high-speed rolling bearings, that relates traction coefficient with normal load, rolling velocity, and lubricant inlet temperature. The coefficients of the formula may be computed by regression analysis of the experimental data. Two example calculations are presented. The predicted results from the formula agree well with experimental observations.

Investigation into the traction coefficient in elastohydrodynamic lubrication

Cardiac myxoma is the most common type of human heart tumor, yet the molecular mechanism is still poorly understood. In the present study, we found that the level of myocyte enhancer factor 2D (MEF2D), a key regulatory protein for cardiac development, was elevated in specimens of cardiac myxoma, and was positively associated with the proliferation of myxoma cells. MEF2D suppression reduced the proliferation of myxoma cells and its tumorigenicity. Cell cycle progression was also inhibited by MEF2D suppression. miR-218, which is downregulated in myxoma, suppressed MEF2D expression by targeting its mRNA 3'UTR. Altogether, we found that miR-218/MEF2D may be an effective target for myxoma treatment.

/pdf/mir-218-suppresses-cardiac-myxoma-proliferation-by-targeting-rv1na6qjhv.pdf

miR-218 suppresses cardiac myxoma proliferation by targeting myocyte enhancer factor 2D

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MicroRNA-200c regulates cisplatin resistance by targeting ZEB2 in human gastric cancer cells.

Investigation into the traction coefficient in elastohydrodynamic lubrication

miR-218 suppresses cardiac myxoma proliferation by targeting myocyte enhancer factor 2D