Background Prostate cancer (PCa) is the most frequently diagnosed malignancy in men, and its mechanism remains poorly understood. Therefore, it is urgent to discover potential novel diagnostic biomarkers and therapeutic targets that can potentially facilitate the development of efficient anticancer strategies. Methods A series of functional in vitro and in vivo experiments were conducted to evaluate the biological behaviors of PCa cells. RNA pulldown, Western blot, luciferase reporter, immunohistochemistry and chromatin immunoprecipitation assays were applied to dissect the detailed underlying mechanisms. High-throughput sequencing was performed to screen for differentially expressed circRNAs in PCa and adjacent normal tissues. Results Upregulation of protein arginine methyltransferase 5 (PRMT5) is associated with poor progression-free survival and the activation of multiple signaling pathways in PCa. PRMT5 inhibits the transcription of CAMK2N1 by depositing the repressive histone marks H4R3me2s and H3R8me2s on the proximal promoter region of CAMK2N1, and results in malignant progression of PCa both in vitro and in vivo. Moreover, the expression of circSPON2, a candidate circRNA in PCa tissues identified by RNA-seq, was found to be associated with poor clinical outcomes in PCa patients. Further results showed that circSPON2 induced PCa cell proliferation and migration, and that the circSPON2-induced effects were counteracted by miR-331-3p. Particularly, circSPON2 acted as a competitive endogenous RNA (ceRNA) of miR-331-3p to attenuate the repressive effects of miR-331-3p on its downstream target PRMT5. Conclusions Our findings showed that the epigenetic regulator PRMT5 aggravates PCa progression by inhibiting the transcription of CAMK2N1 and is modulated by the circSPON2/miR-331-3p axis, which may serve as a potential therapeutic target for patients with aggressive PCa.

Objective: Postoperative radiotherapy for breast cancer is an effective way to control tumor recurrence; however, there are advantages and disadvantages to different radiotherapy techniques. This study compared dosimetry differences between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) plans after radical surgery for left-sided breast cancer to provide guidance for clinicians to select a radiotherapy technique.Methods: A total of 50 women who received radiation therapy for left-sided breast cancer after radical surgery in Gansu Provincial Cancer Hospital between 9 January 2017 and 30 November 2017 were included. The prescription dose was 50 Gy/25f. IMRT and 3D-CRT treatment plans were designed for each patient on an Oncentra 4.1 planning system. Statistical analysis of the target dose distribution -conformal index, uniformity index, and irradiation doses to the ipsilateral lung, heart, left ventricle, humeral head, and thyroid -was carried out for the two groups and the differences were compared.Results: When comparing the two plans, the target V 95% (z = -5.739, P < 0.001), V 105% (t = -3.244, P = 0.002), V 110% (t = -9.420, P < 0.001), V 115% (z = −5.834, P < 0.001), conformal index (t = 27.711, P < 0.001), and uniformity index (t = -15.761, P < 0.001) for the IMRT plan were better than those for the 3D-CRT plan. Meanwhile, V 30 (t = -4.29, P < 0.001) and the maximum dose (z = -5.285, P < 0.001) of the ipsilateral lung, V 40 (z = -4.294, P < 0.001) and V 50 (z = -5.873, P < 0.001) of the heart, V 40 (z = -4.918, P < 0.001) and V 50 (z = -5.633, P < 0.001) of the left ventricle, and V 50 (z = -4.196, P < 0.001) of the humeral head in the IMRT plan were lower than those in the 3D-CRT plan. However, V 5 (t = 30.086, P < 0.001), V 10 (z = −6.154, P < 0.001), V 20 (t = 8.228, P < 0.001), and the mean dose (z = −4.156, P < 0.001) of the ipsilateral lung, V 30 (z = -4.407, P < 0.001) and the mean dose (t = 17.877, P < 0.001) of the heart, V 30 (z = −2.920, P = 0.003) and the mean dose (t = 15.324, P < 0.001) of left ventricle, the mean dose (z = −6.144, P < 0.001) of the humeral head, and V 40 (z = -6.154, P < 0.001) and the mean dose (z = -5.643, P < 0.001) of the thyroid in the IMRT plan were higher than those in the 3D-CRT plan. There was no statistically significant difference in the V 50 (t = 0.825, P = 0.413) of the thyroid between the IMRT and 3D-CRT plans.

BackgroundRenal clear cell cancer (ccRCC) is one of the most common cancers in humans. Thus, we aimed to construct a risk model to predict the prognosis of ccRCC effectively.MethodsWe downloaded RNA sequencing (RNA-seq) data and clinical information of 539 kidney renal clear cell carcinoma (KIRC) patients and 72 normal humans from The Cancer Genome Atlas (TCGA) database and divided the data into training and testing groups randomly. Pyroptosis-related lncRNAs (PRLs) were obtained through Pearson correlation between pyroptosis genes and all lncRNAs (p &lt; 0.05, coeff &gt; 0.3). Univariate and multivariate Cox regression analyses were then performed to select suitable lncRNAs. Next, a novel signature was constructed and evaluated by survival analysis and ROC analysis. The same observation applies to the testing group to validate the value of the signature. By gene set enrichment analysis (GSEA), we predicted the underlying signaling pathway. Furthermore, we calculated immune cell infiltration, immune checkpoint, the T-cell receptor/B-cell receptor (TCR/BCR), SNV, and Tumor Immune Dysfunction and Exclusion (TIDE) scores in TCGA database. We also validated our model with an immunotherapy cohort. Finally, the expression of PRLs was validated by quantitative PCR (qPCR).ResultsWe constructed a prognostic signature composed of six key lncRNAs (U62317.1, MIR193BHG, LINC02027, AC121338.2, AC005785.1, AC156455.1), which significantly predict different overall survival (OS) rates. The efficiency was demonstrated using the receiver operating characteristic (ROC) curve. The signature was observed to be an independent prognostic factor in cohorts. In addition, we found the PRLs promote the tumor progression via immune-related pathways revealed in GSEA. Furthermore, the TCR, BCR, and SNV data were retrieved to screen immune features, and immune cell scores were calculated to measure the effect of the immune microenvironment on the risk model, indicating that high- and low-risk scores have different immune statuses. The TIDE algorithm was then used to predict the immune checkpoint blockade (ICB) response of our model, and subclass mapping was used to verify our model in another immunotherapy cohort data. Finally, qPCR validates the PRLs in cell lines.ConclusionThis study provided a new risk model to evaluate ccRCC and may be pyroptosis-related therapeutic targets in the clinic.

Background: Extensive research has revealed that genes play a pivotal role in tumor development and growth. However, the underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further.Methods: In this study, we identified overlapping differentially expressed genes (DEGs) by comparing tumor tissue with adjacent normal tissue using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database.Results: Our analysis identified 79 up-regulated and ten down-regulated genes. Functional enrichment analysis and prognosis analysis were conducted on the identified genes, and the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2, was chosen for more detailed analysis. We performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations, and checkpoints) to elucidate the mechanisms of action of ALDH3A2 in depth. The immunohistochemical (IHC) result based on 140 paraffin-embedded human GC samples indicated that ALDH3A2 was over-expressed in low-grade GC cases and the OS of patients with low expression of ALDH3A2 was significantly shorter than those with high ALDH3A2 expression. In vitro results indicated that the expression of ALDH3A2 was negatively correlated with PDCD1, PDCD1LG2, and CTLA-4.Conclusion: We conclude that ALDH3A2 might be useful as a potential reference value for the relief and immunotherapy of GC, and also as an independent predictive marker for the prognosis of GC.