Unveiling key oncogenic events in malignancies is the key to improving the prognosis and therapeutic outcome of malignancies. Lines of evidence have shown that super-enhancers control the expression of genes that determine the cell fate, but the oncogenic super-enhancers in colorectal cancer (CRC) and their impact on carcinogens remain largely unexplored. Here, we identified a new oncogenic super-enhancer-regulated gene, IL-20RA, in CRC. Using the integrative analysis of H3K27ac ChIP-seq and RNA-seq in CRC tumors and normal colon tissues, we obtained a series of oncogenic super-enhancers in CRC. We found that super-enhancer inhibition by JQ-1 or iBET-151 suppressed the growth of tumor cells and inhibited the expression of IL-20RA. We found that IL-20RA was highly expressed in the tumor tissue of CRC and related to the advanced stage. Further functional studies showed that knockdown of IL-20RA inhibited the growth and metastasis of CRC. In addition, we found that IL-20RA was involved in regulating oncogenic and immune pathways and affecting the expression of genes related to cell proliferation and immune evasion in CRC. Together, our study demonstrated a novel oncogene in CRC and shed new light on oncogenic super-enhancer contributions to cell proliferation and immune escape.

Objective: To evaluate the performance of a T2-weighted image (T2WI)-based radiomics signature for differentiating between seminomas and nonseminomas. Materials and Methods: In this retrospective study, 39 patients with testicular germ-cell tumors (TGCTs) confirmed by radical orchiectomy were enrolled, including 19 cases of seminomas and 20 cases of nonseminomas. All patients underwent 3T magnetic resonance imaging (MRI) before radical orchiectomy. Eight hundred fifty-one radiomics features were extracted from the T2WI of each patient. Intra- and interclass correlation coefficients were used to select the features with excellent stability and repeatability. Then, we used the minimum-redundancy maximum-relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithms for feature selection and radiomics signature development. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of the radiomics signature. Results: Five features were selected to build the radiomics signature. The radiomics signature was significantly different between the seminomas and nonseminomas (p < 0.01). The area under the curve (AUC), sensitivity, and specificity of the radiomics signature for discriminating between seminomas and nonseminomas were 0.979 (95% CI: 0.873-1.000), 90.00 (95% CI: 68.3-98.8), and 100.00 (95% CI: 82.4-100.0), respectively. Conclusion: The T2WI-based radiomics signature has the potential to non-invasively discriminate between seminomas and nonseminomas.

Pancreatic cancer is one of the major reasons of cancer-associated deaths due to poor diagnosis, high metastasis and drug resistance. Therefore, it is important to understand the cellular and molecular mechanisms of pancreatic cancer to identify new targets for the treatment. TIPE2 is an essential regulator of tumor apoptosis, inflammation and immune homeostasis. However, the role of TIPE2 is still not fully understood in pancreatic cancer. In this study, we found the expression of TIPE2 was decreased in pancreatic cancer tissues compare to paracancerous tissues, which was negatively correlated with tumor size in patients. Overexpression of TIPE2 significantly decreased cell proliferation, metastasis and increased apoptotic events in pancreatic cancer cell lines. Moreover, the results obtained from real time PCR and western blot revealed that TIPE2 was also involved in inhibiting MMPs and N-Cadherin expression while increasing Bax expression in pancreatic cancer cells. Similarly, TIPE2 could inhibit tumor growth in vivo, decrease the expression of Ki-67 and N-Cadherin, and increase the expression of Bax by IHC analysis in tumor tissues isolated from tumor-bearing mice. Mechanistic studies exhibited that TIPE2 might suppress pancreatic cancer development through inhibiting PI3K/AKT and Raf/MEK/ERK signaling pathways triggered by TGFβ1. Moreover, the tumor-infiltrating lymphocytes from tumor-bearing mice were analyzed by flow cytometry, and showed that TIPE2 could promote T cell activation to exert an anti-tumor effect possibly through activation of DCs in a TGFβ1 dependent manner. In general, we described the multiple regulatory mechanisms of TIPE2 in pancreatic tumorigenesis and tumor microenvironment, which suggested TIPE2 may act as a potential therapeutic target in pancreatic cancer.