Exosomes have been associated with chemoresistance in various cancers, but such a role in ovarian cancer is not yet clear. Here, using in vitro cell-based and in vivo mouse model experiments, we show that downregulation of O-GlcNAcylation, a key post-translational protein modification, promotes exosome secretion. This increases exosome-mediated efflux of cisplatin from cancer cells resulting in chemoresistance. Mechanistically, our data indicate that downregulation of O-GlcNAclation transferase (OGT) reduces O-GlcNAclation of SNAP-23. Notably, O-GlcNAcylation of SNAP-23 is vital for regulating exosome release in ovarian cancer cells. Reduced O-GlcNAclation of SNAP-23 subsequently promotes the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of SNAP-23, VAMP8, and Stx4 proteins. This enhances exosome release causing chemoresistance by increasing the efflux of intracellular cisplatin.
The incidence of endometrial cancer (EC) is rapidly increasing worldwide. The majority of endometrial cancers are diagnosed at an early stage and are associated with a good prognosis; however, patients with advanced-stage EC have a poor prognosis and present with invasive metastasis. The mechanisms responsible for the invasion and metastasis of endometrial cancer remain unknown. Here, the present study aimed to examine the effects of
O
-GlcNAcylation on the malignancy of EC and its association with Yes-associated protein (YAP). It was found that the expression of
O
-GlcNAc transferase (OGT) and
O
-GlcNAcylation were increased in EC tissues; the decrease in
O
-GlcNAcylation levels was found to lead to the decreased proliferation, migration and invasion of EC cells. Mass spectrometric analysis revealed that OGT knockdown reduced the
O
-GlcNAcylation of YAP. Furthermore, it was found that the reduction in the
O
-GlcNAcylation of YAP promoted its phosphorylation, which in turn inhibited the access of YAP to the nucleus and downstream target gene activation, demonstrating that the level of
O
-GlcNAcylation affects the development of EC. On the whole, the findings of the present study indicate that YAP is a key molecule linking the
O
-GlcNAcylation and Hippo pathways, which together regulate the progression of EC.
The diagnosis of prostate transition zone cancer (PTZC) remains a clinical challenge due to their similarity to benign prostatic hyperplasia (BPH) on MRI. The Deep Convolutional Neural Networks (DCNNs) showed high efficacy in diagnosing PTZC on medical imaging but was limited by the small data size. A transfer learning (TL) method was combined with deep learning to overcome this challenge.
Materials and methodsA retrospective investigation was conducted on 217 patients enrolled from our hospital database (208 patients) and The Cancer Imaging Archive (nine patients). Using T2-weighted images (T2WIs) and apparent diffusion coefficient (ADC) maps, DCNN models were trained and compared between different TL databases (ImageNet vs. disease-related images) and protocols (from scratch, fine-tuning, or transductive transferring).
ResultsPTZC and BPH can be classified through traditional DCNN. The efficacy of TL from natural images was limited but improved by transferring knowledge from the disease-related images. Furthermore, transductive TL from disease-related images had comparable efficacy to the fine-tuning method. Limitations include retrospective design and a relatively small sample size.
ConclusionDeep TL from disease-related images is a powerful tool for an automated PTZC diagnostic system. In developing regions where only conventional MR scans are available, the accurate diagnosis of PTZC can be achieved via transductive deep TL from disease-related images.
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