Pancreatic adenocarcinoma is one of the leading lethal human cancer types and is notorious for its poor prognosis. A series of bioinformatic analyses and experimental validations were employed to explore the role and mechanism of pseudogene-derived RNAs in pancreatic adenocarcinoma. Consequently, a total of 13 upregulated and 7 downregulated pseudogene-derived RNAs in pancreatic adenocarcinoma were identified. Survival analysis revealed a statistically predictive role of AK4P1 for unfavourable prognosis of patients with pancreatic adenocarcinoma. Subcellular location analysis indicated that AK4P1 was mainly located in cytoplasm, in which AK4P1 might competitively bind to tumour suppressive miR-375 in pancreatic adenocarcinoma. Further analysis showed that SP1 was a potential downstream target gene of miR-375 in pancreatic adenocarcinoma. Intriguingly, expression determination validated that SP1 could positively regulate AK4P1 levels in pancreatic adenocarcinoma. Finally, AK4P1 might also exert its effects by interacting with oncogenic parental gene AK4 in pancreatic adenocarcinoma. Conclusively, the present study elucidated a key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma.

Objectives Limonin has received significant attention due to its multiple biological effects, intervertebral disc degeneration (IDD) is also of interest due to the high prevalence of this disease. In this study, we determined the effects of limonin on IDD and the underlying mechanism of action to find novel ways to treat IDD. Methods An IL-1β-induced cell inflammation model and a lumbar instability model inducing IDD were established to assess the progression of IDD with or without limonin treatment. We further evaluated MAPK/NF-κB and necroptosis pathways and alterations in the extracellular matrix specific within the disc. Key findings Limonin suppresses inflammation in the nucleus pulposus in vitro by reducing the production of pro-inflammatory markers such as iNOS and COX-2. Limonin reduced the activation of the MAPK/NF-κB signalling pathway and the RIP1/RIP3/MLKL necroptosis pathway in the NP cells. Moreover, limonin delays the IDD progression in the lumbar instability model. Conclusions Limonin could potentially delay IDD by inhibiting NP cell necroptosis and modulating peripheral matrix proteins within the intervertebral disc and is a potential pharmacological research direction for the therapy in patients with IDD.

Background Breast cancer ranks second in female tumor mortality, with an estimation of 2 million new cases diagnosed each year worldwide. Methods In our current study, we screened 13 genes highly distributed on the P53 phenotype which were significantly expressed and had a strong correlation with survival in the Cancer Genome Atlas breast cancer dataset. Least absolute shrinkage and selection operator Cox regression was conducted to construct the risk assessment model. Based on bioinformatics and statistical methods, we confirmed the credibility and validity of the model by training set and testing set. Results The result of comparing the other two previous hypoxia models was also satisfying. We also verified the model on one of the Gene Expression Omnibus datasets—GSE20685. Using clinical data from patients in the Cancer Genome Atlas, we acknowledged the risk score as an independent influence on breast cancer survival prognosis, and strong relevance was suggested between risk signature and age, lymphatic metastasis, tumor size and clinical stage by performing univariate and multivariate analysis. Immunology analysis demonstrated that the macrophages subset was positively associated with a risk score and other immune cell types had a negative effect with the risk score increases. The risk score was also emerging as a valuable prognostic factor for the prediction of chemotherapy drug curative effect because Gemcitabine, vinorelbine, paclitaxel and cisplatin known as a generic drug for breast cancer had more pleasing sensitivity in high-scored patients than low-scored patients. Conclusion The P53-related risk assessment model is promising to be a potential predictor for the prognosis of patients with breast cancer and a powerful guide for the selection of therapeutic strategies.

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Background: Anoikis, a mechanism of programmed apoptosis, plays an important role in growth and metastasis of tumors. However, there are still few available comprehensive reports on the impact of anoikis on colorectal cancer. Method: A clustering analysis was done on 133 anoikis-related genes in GSE39582, and we compared clinical features between clusters, the tumor microenvironment was analyzed with algorithms such as “Cibersort” and “ssGSEA”. We investigated risk scores of clinical feature groups and anoikis-associated gene mutations after creating a predictive model. Lastly, we incorporated clinical traits to build a nomogram. Result: We identified two anoikis-related clusters with distinct prognoses, clinical characteristics, and biological functions. One of the clusters was associated with anoikis resistance, which activated multiple pathways encouraging tumor metastasis. In our prognostic model, oxaliplatin may be a sensitive drug for low-risk patients. The nomogram showed good ability to predict survival time. Conclusion: Our study identified two distinct modes of anoikis in colorectal cancer, with active metastasis-promoting pathways inducing an anti-anoikis subtype, which has a stronger propensity for metastasis and a worse prognosis than an anoikis-activated subtype. Massive immune cell infiltration may be an indicator of anoikis resistance. Anoikis' role in the colorectal cancer remains to be investigated.