The zinc-finger transcription factor Snail1 is inappropriately expressed in breast cancer and associated with poor prognosis. While interrogating human databases, we uncovered marked decreases in relapse-free survival of breast cancer patients expressing high Snail1 levels in tandem with wild-type, but not mutant, p53. Using a Snail1 conditional knockout model of mouse breast cancer that maintains wild-type p53, we find that Snail1 plays an essential role in tumour progression by controlling the expansion and activity of tumour-initiating cells in preneoplastic glands and established tumours, whereas it is not required for normal mammary development. Growth and survival of preneoplastic as well as neoplastic mammary epithelial cells is dependent on the formation of a Snail1/HDAC1/p53 tri-molecular complex that deacetylates active p53, thereby promoting its proteasomal degradation. Our findings identify Snail1 as a molecular bypass that suppresses the anti-proliferative and pro-apoptotic effects exerted by wild-type p53 in breast cancer.

Lung adenocarcinoma is the most prevalent type of lung cancer with a high incidence and mortality worldwide. Metastasis is the major cause of high death rate in lung cancer and the potential mechanism of lung adenocarcinoma metastasis remains indistinct. Emerging investigations have demonstrated that long noncoding RNA is a kind of non–protein coding RNA and plays a critical role in cancer progression and metastasis. TTN antisense RNA 1 (TTN‐AS1) has been reported to promote cell growth and metastasis in cancer. However, the function of TTN‐AS1 in lung adenocarcinoma is still to be illustrated. In this study, we observed that TTN‐AS1 was upregulated in tissues and cells of lung adenocarcinoma and associated with poor overall survival. TTN‐AS1 promoted cell proliferation, migration, invasion, and epithelial‐mesenchymal transition in lung cancer. TTN‐AS1 directly bound with miR‐4677‐3p and negatively regulated miR‐4677‐3p. MiR‐4677‐3p rescued the inhibitive impacts of TTN‐AS1 knockdown on lung adenocarcinoma. Furthermore, zinc finger E‐box binding homeobox 1 (ZEB1) was the target of miR‐4677‐3p, and TTN‐AS1 modulated ZEB1 by competing for miR‐4677‐3p. TTN‐AS1 drove the invasion and migration of lung adenocarcinoma cells by targeting the miR‐4677‐3p/ZEB1 axis. To sum up, our study offers insights into the mechanism of TTN‐AS1 in lung adenocarcinoma metastasis and targeting the TTN‐AS1/miR‐4677‐3p/ZEB1 axis may be the potential innovate therapeutic strategy for the patients with lung adenocarcinoma.

Uridine phosphorylase 1 (UPP1) has been reported as an oncogene in several malignancies. In glioma, the role of UPP1 remains unclear. This study was performed to explore its role in glioma at transcriptional level. Totally, 998 glioma patients with clinical data were enrolled, including 301 mRNA microarray data from Chinese Glioma Genome Atlas (CGGA) dataset and 697 RNAseq data from The Cancer Genome Atlas (TCGA) dataset. Statistical analysis was performed with R language. UPP1 expression level was positively correlated with WHO grade of glioma. UPP1 was significantly upregulated in mesenchymal subtype and could serve as a potential biomarker for this subtype. Based on most correlated genes of UPP1, Gene ontology analysis revealed that UPP1 was profoundly associated with immune and inflammatory response. Gene Sets Variation Analysis was further performed and showed that UPP1 was particularly correlated with MHC‐II and LCK, which were mainly associated with activities of antigen‐presenting cells and T cells. Moreover, UPP1 was found to be synergistic with various immune checkpoint members, especially with PD1 pathway and B7‐H3. Finally, Kaplan‐Meier curves revealed that higher UPP1 indicated significantly shorter survival for glioma patients. Taken together, UPP1 played an oncogenic role in glioma via suppressing tumor‐related immune response.

Background This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity. Methods A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration. Results 4SCAR-T cells expanded for 1–3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion. Conclusion Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted. Trial registration ClinicalTrials.gov Identifier: NCT03170141. Registered 30 May 2017.