Whole transcriptome sequencing identifies a competitive endogenous RNA network that regulates the immunity of bladder cancer.

Several types of non-coding RNAs such as circRNAs, lncRNAs, and miRNAs have been identified to regulate mRNAs through the mechanism known as the competitive endogenous RNA (ceRNA) network. To explore the role of the ceRNA regulatory network in the immune microenvironment of bladder cancer, whole-transcriptome sequencing of bladder tumor and its peritumoral tissues from 38 bladder cancer patients, with a total of 63 samples, was performed to screen differentially expressed circ-, lnc-, mi-, and mRNAs to construct a circ/lnc-mi-mRNA regulatory network with pruning algorithms. We excavated a key immune-related gene BDNF to build the final ceRNA network as hsa-miR-107 sponged by hsa-circ-000211, AC108488.1, and LINC00163. Finally, a meta-analysis of 7 public datasets demonstrated that low expression of BDNF and high expression of hsa-miR-107 were associated with longer survival. Our study identified a ceRNA regulatory network as a potentially new prognostic marker and molecular therapeutic target of bladder cancer.

Primary malignant melanoma of the male urethra: a case report.

We present a rare case of a 69-year-old male patient with serendipitous urethral melanoma. He complained of dysuria and recurrent urinary retention and was initially diagnosed with benign prostatic hyperplasia. Accidentally, a dark-brown pigmented macula was found in the distal urethra at the end of transurethral prostatectomy when we exited the resectoscope, transurethral resection of the nidus and sent to pathological examination showed the characteristics of melanoma. No other lesions were found on further examination and the patient preferred a close follow-up cystoscopy rather than an immediate urethrectomy. Unsurprisingly, he relapsed in the urethra with the local disease three months later and we treated him with partial urethrectomy, followed by watchful waiting for 11 months. However, the patient was readmitted for hematuria, and 18F-FDG PET-CT showed a large number of pelvic and bone metastatic lesions. Therefore, eight cycles of single-agent dacarbazine chemotherapy were administered, and the disease was demonstrated prolonged stabilization. Follow-up was conducted every 3 months, during which time palliative transurethral resection of the melanoma in the bladder was performed to control urinary tract infections. Although the prognosis of the disease is extremely poor, this patient has gained more than 50 months of overall survival and is alive to date.

WASF3 Knockdown Sensitizes Gastric Cancer Cells to Oxaliplatin by Inhibiting ATG12-Mediated Autophagy.

BACKGROUND: Gastric cancer is one of the most aggressive tumors, usually resulting in metastasis, and therapies for advanced gastric cancer remain limited. Drug resistance is the main reason for chemotherapeutic failure in gastric cancer. Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion and metastasis of different cancers. However, there has been little study of WASF3 expression involvement in gastric cancer. In this study, we explored the role of WASF3 in the sensitivity of gastric cancer to oxaliplatin, and the underlying mechanisms. METHODS: We silenced WASF3 using WASF3-siRNA in MGC803 cells. Then, CCK-8, flow cytometry and transwell assay were performed to study the effect of WASF3 silencing on proliferation, migration, invasiveness and apoptosis of MGC803 cells. Moreover, we evaluated the potential mechanism in vitro to determine the sensitization to oxaliplatin induced by WASF3. RESULTS: WASF3 silencing by small interfering RNA inhibited the proliferation, migration and invasiveness of gastric cancer cells. We also observed that WASF3 knockdown promoted cell apoptosis and enhanced oxaliplatin sensitivity. Furthermore, the sensitization to oxaliplatin induced by WASF3 knockdown depended on the inhibition of Atg12-mediated autophagy. CONCLUSIONS: Our analysis demonstrates WASF3 targeting is a new potential therapeutic strategy for gastric cancer.

WASF3 expression correlates with poor prognosis in gastric cancer patients.

Aim: WASF3 has been shown to be required for invasion and metastasis in different cancers, this study is to explore the prognostic value of WASF3 in gastric cancer. Materials & methods: The coexpression of WASF3 and E-cadherin in gastric cancer patients and cells were evaluated. Results: WASF3 was overexpressed and the expression of E-cadherin was decreased in gastric cancer tissues compared with normal tissues (p < 0.001). WASF3 expression is associated with decreased expression of E-cadherin (p = 0.002). Patients with WASF3-positive expression had a poorer prognosis. The multivariate analysis showed that WASF3 expression is an independent prognostic factor related to overall survival (p = 0.027). Conclusion: Our analysis demonstrates that WASF3 expression correlates with poor outcomes and is a potential prognostic factor in gastric cancer patients.

A novel heterozygous large deletion of MSH6 gene in a Chinese family with Lynch syndrome.

Lynch syndrome (LS) is a common cancer syndrome that is inherited in an autosomal dominant manner. Its pathogenesis is thought to be closely related to germline mutations of mismatch repair (MMR) genes such as the MLH1, MSH2, PMS2 and MSH6 genes. This study identifies a Chinese family with LS clinically diagnosed according to the Amsterdam II criteria. In these patients, immuno-histochemical staining showed negative MSH6 expressions but positive MLH1, MSH2, and PMS2 expressions. In order to further explore the molecular biology of this LS family, we used targeted next-generation sequencing (NGS) and Multiplex ligation dependent probe amplification (MLPA) to identify the mutation and verify the authenticity of the mutation in 15 family members. For NGS, two panels have been used, one is of MLH1, MSH2, PMS2 and MSH6 genes, the other one is of 139 cancer genetic susceptibility genes. And for the large deletions/duplications can also be identified by NGS panel, an adjusted data analysis strategy of NGS has been used. As a result, we identified a novel heterozygous large deletion in MSH6 gene that was found to be co-segregated among affected family members. This deletion results in the loss of a 3246 bp-sized fragment in MSH6 gene exons 5-9 which represents the coding regions of the MSH6 ATPase domain. This novel mutation has yet to be documented in the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) database. This mutation resulted in MSH6 protein losing gene mismatch repair function, and further caused the microsatellite instable. We speculate that this mutation may significantly impact MMR function through impaired ATP domain function. Theoretically, this proband would likely benefit from PD-1 immune check-point blockade therapy, but conversely, we observed that tumors appeared to rapidly progress after 4 sessions of anti-PD-1 treatment. Further studies to validate the effectiveness of anti-PD-1 treatments in carriers of this mutation are necessary.