Involvement of the oncogenic small nucleolar RNA SNORA24 in regulation of p53 stability in colorectal cancer.

Colorectal cancer (CRC) is a common malignant cancer worldwide. Although the molecular mechanism of CRC carcinogenesis has been studied extensively, the details remain unclear. Small nucleolar RNAs (snoRNAs) have recently been reported to have essential functions in carcinogenesis, although their roles in CRC pathogenesis are largely unknown. In this study, we found that the H/ACA snoRNA SNORA24 was upregulated in various cancers, including CRC. SNORA24 expression was significantly associated with age and history of colon polyps in CRC patient cohorts, with high expression associated with a decreased 5-year overall survival. Our results indicated that the oncogenic function of SNORA24 is mediated by promoting G1/S phase transformation, cell proliferation, colony formation, and growth of xenograft tumors. Furthermore, SNORA24 knockdown induced massive apoptosis. RNA-sequencing and gene ontology (GO) enrichment analyses were performed to explore its downstream targets. Finally, we confirmed that SNORA24 regulates p53 protein stability in a proteasomal degradation pathway. Our study clarifies the oncogenic role of SNORA24 in CRC and advance the current model of the role of the p53 pathway in this process.

SNORD15B and SNORA5C: Novel Diagnostic and Prognostic Biomarkers for Colorectal Cancer.

Colorectal cancer (CRC) is presenting a global public health problem with high incidence and mortality. Early diagnosis and treatment are the most important strategies to improve prognosis of this disease. Besides fecal occult blood test (FOBT) and colonoscopy, the most widely used methods for CRC screening currently, more effective methods for early diagnosis or prognostic prediction for CRC are needed. Small nucleolar RNAs (snoRNAs) is a class of noncoding RNAs (ncRNAs) playing crucial roles in carcinogenesis and considered to be promising tumor biomarker. In this study, we found that SNORD15B, SNORD48, and SNORA5C were significantly upregulated in CRC tissues. High levels of SNORD15B, SNORD48, or SNORA5C predicted poor clinical outcomes of CRC patients. Forced expression of SNORD15B or SNORA5C in CRC cells promoted proliferation and colony formation. In a further investigation, association between the level of SNORD15B/SNORA5C and clinicopathological parameters of CRC patient cohorts was analyzed based on data from The Cancer Genome Atlas (TCGA). We found that high expressions of SNORD15B and SNORA5C were significantly associated with age, lymphatic invasion, and history of colon polyps, and they were proved to be independent risk factors for survival of CRC patients. This study confirms that SNORD15B and SNORA5C have oncogenic effects in carcinogenesis of CRC. The findings suggest the two genes as potential diagnostic and prognostic biomarkers for CRC.

Corynoxine Protects Dopaminergic Neurons Through Inducing Autophagy and Diminishing Neuroinflammation in Rotenone-Induced Animal Models of Parkinson's Disease.

Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson's disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the substantia nigra pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.

Iron Dysregulation in Parkinson's Disease: Focused on the Autophagy-Lysosome Pathway.

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). Although both iron accumulation and a defective autophagy-lysosome pathway contribute to the pathological development of PD, the connection between these two causes is poorly documented. The autophagy-lysosome pathway not only responds to regulation by iron chelators and channels but also participates in cellular iron recycling through the degradation of ferritin and other iron-containing components. Previously, ferritin has been posited to be the bridge between iron accumulation and autophagy impairment in PD. In addition, iron directly interacts with α-synuclein in Lewy bodies, which are primarily digested through the autophagy-lysosome pathway. These findings indicate that some link exists between iron deposition and autophagy impairment in PD. In this review, the basic mechanisms of the autophagy-lysosome pathway and iron trafficking are introduced, and then their interaction under physiological conditions is explained. Finally, we finish by discussing the dysfunction of iron deposition and autophagy in PD, as well as their potential relationship, which will provide some insight for further study.