The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of tumorigenesis and development. In recent years, the CRISPR/Cas9 system has been increasingly used in cancer research and treatment and remarkable results have been achieved. In this review, we introduced the mechanism and development of the CRISPR/Cas9-based gene editing system. Furthermore, we summarized current applications of this technique for basic research, diagnosis and therapy of cancer. Moreover, the potential applications of CRISPR/Cas9 in new emerging hotspots of oncology research were discussed, and the challenges and future directions were highlighted.

Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and may even progress to dementia. However, the underlying mechanism of altered functional topological organization and cognitive impairments remains unclear. This study explored the topological properties of functional whole brain networks in T2DM patients with graph theoretical analysis using a resting-state functional magnetic resonance imaging (rs-fMRI) technique. Thirty T2DM patients (aged 51.77 ± 1.42 years) and 30 sex-, age-, and education-matched healthy controls (HCs) (aged 48.87 ± 0.98 years) underwent resting-state functional imaging in a 3.0 T MR scanner in addition to detailed neuropsychological and laboratory tests. Then, graph theoretical network analysis was performed to explore the global and nodal topological alterations in the functional whole brain networks of the T2DM patients. Finally, correlation analyses were performed to investigate the relationship between the altered topological parameters, cognitive performances and clinical variables. Compared to HCs, we found that T2DM patients displayed worse performances in general cognitive function and several cognitive domains, including episodic memory, attention and executive function. In addition, T2DM patients showed a higher small-worldness (σ), a higher normalized clustering coefficient (γ) and a higher local efficiency (E loc ). Moreover, decreased nodal topological properties were mainly distributed in the occipital lobes, frontal lobes, left median cingulate and paracingulate gyri, and left amygdala, while increased nodal topological properties were mainly distributed in the right gyrus rectus, right anterior cingulate and paracingulate gyri, right posterior cingulate gyrus, bilateral caudate nucleus, bilateral cerebellum 3, bilateral cerebellum crus 1, vermis (1, 2) and vermis 3. Some disrupted nodal topological properties were correlated with cognitive performance and HbA1c levels in T2DM patients. This study shows altered functional topological organization in T2DM patients, mainly suggesting a compensation mechanism of the functional whole brain network in the relatively early stage to counteract cognitive impairments.

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Background: Hypoxia-induced chemoresistance is recognized as a major obstacle to the successful treatment of gastric cancer (GC). Circular RNAs (circRNAs) have been proposed to implicate in resistance to chemotherapeutic drugs. However, whether circNRIP1 is involved in the development of hypoxia-induced 5-fluorouracil (5-FU) resistance remains largely unknown. Methods: Gene expression was evaluated using quantitative real-time polymerase chain reaction and Western blot. The impact of circNRIP1 on hypoxia-induced resistance to 5-FU was investigated by determining glucose consumption, lactate production and glucose-6-phosphate (G6P) levels. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide assay was performed to assess cell survival. Results: circNRIP1 was upregulated in GC cells. Hypoxia induced the upregulation of circNRIP1 and reduced the sensitivity of GC cells to 5-FU, as evidenced by the increase in multidrug resistance 1 gene, P-glycoprotein, hypoxia-inducible factor-1α (HIF-1α) and G6P levels, glucose consumption, lactate production, as well as cell survival. Silencing of circNRIP1 enhanced the sensitivity of GC cells to 5-FU under a hypoxic condition. microRNA (miR)-138-5p was confirmed as a downstream target gene of circNRIP1, and upregulation of miR-138-5p could reverse the effect of circNRIP1 on hypoxia-induced 5-FU resistance. Additionally, HIF-1α was a target gene of miR-138-5p. More significantly, the effect of circNRIP1 on hypoxia-induced 5-FU resistance was markedly blocked by 2-DG treatment. Conclusion: circNRIP1 functioned as a miR-138-5p sponge to enhance hypoxia-induced resistance to 5-FU through modulation of HIF-1α-dependent glycolysis, which provides a novel potential approach to overcome hypoxia-induced 5-FU resistance in GC.