RESUMO
Cisplatin is the first-line chemotherapy for gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which leads to poor prognosis in GC patients. Recently, evidence has revealed that circular RNAs (circRNAs) and dysregulation of autophagy-dependent ferroptosis play critical roles in cancer chemoresistance. Herein, for the first time we report that circHIPK3 has a vital role in GC cisplatin resistance. CircHIPK3 regulated cisplatin resistance by targeting autophagy and ferroptosis. In brief, knockdown circHIPK3 decreased GC cell cisplatin resistance by enhancing ferroptosis via the miR-508-3p/Bcl-2/beclin1/SLC7A11 axis. Taken together, our results demonstrate that ferroptosis is a promising strategy to ameliorate cisplatin resistance. Importantly, serum exosomal circHIPK3 could also be a noninvasive indicator to evaluate cisplatin resistance in GC.
RESUMO
Prostate cancer (PCa) is one of the most common cancers in men worldwide. Early diagnosis of PCa is extremely challenging due to the lack of effective diagnostic methods. The study presented here aims to evaluate whether urine volatile organic compounds (VOCs) can be used as an emerging diagnostic biomarker for PCa. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in urine samples from 66 patients with PCa and to comparatively analyze samples from 87 patients with non-cancerous controls (NCs). A total of 86 substance peak heights were detected in urine samples from all patients. Analysis using four machine learning algorithms suggested that the diagnosis of PCa could be effectively facilitated. Ultimately, diagnostic models were constructed based on the four VOCs selected. The AUC for the RF and SVM model were 0.955 and 0.981, respectively. Both the NN and DT diagnostic models also achieved an AUC of 0.8 or more, but their sensitivity or specificity was poor compared to the RF and SVM models.
RESUMO
Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.
Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fusobacterium nucleatum/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Proliferação de Células/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.
