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Background: To explore the biological and clinical effects of titin-antisense RNA1 (TTN-AS1) in bladder cancer (BC) and the association between TTN-AS1 and activating transcription factor 2 (ATF2) in BC.Methods: The Kaplan–Meier method was performed to analyze the association between the expression of TTN-AS1 and prognosis of BC patients from TCGA data set and our institution. Quantitative real-time PCR (RT-PCR) was conducted to explore the expression of TTN-AS1 between the patients who underwent TURBT and Re-TURBT. MTT, colony formation, and tumor formation assays were conducted to evaluate the effect of TTN-AS1 on the ability of proliferation in BC cell lines. Transwell assay was performed to evaluate the effect of TTN-AS1 on the ability of invasion in BC cell lines. Bioinfomatics and immunohistochemical staining was used to identify the relationship between TTN-AS1 and ATF2.Results: The higher expression of TTN-AS1 was related to poorer disease-free survival (DFS) in patients with BC. The expression of TTN-AS1 was higher in BC patients who underwent Re-TURBT compared with BC patients who underwent TURBT. Knocking down TTN-AS1 resulted in inhibiting the ability of proliferation and invasion of BC cells. ATF2 may serve as a downstream target of TTN-AS1 in BC, and the high expression of ATF2 is also related to adverse DFS.Conclusion: Our study reveals that TTN-AS1 serves as an oncogene by activating ATF2 in BC. The findings suggest that TTN-AS1 may act as a novel therapeutic target for patients with BC.

Vasohibin-1 (VASH1) has recently been isolated as a novel inhibitor of angiogenesis. Several studies have demonstrated that VASH1 plays important roles in tumor angiogenesis but the role of this angiogenic inhibitor in renal cell carcinoma (RCC) has not been elucidated. We previously reported that VASH1 expression is reduced and is associated with clinicopathological features in RCC. In the present study, we investigated the biological effects of VASH1 in RCC by evaluating the effects of VASH1 on cell proliferation, cell cycle distribution, cell apoptosis and cell invasion in human umbilical vein endothelial cells (HUVECs) and 786-0 cells, and evaluating the effect of VASH1 on the growth of 786-0 cells in nude mice. A pReceiver-M61-VASH1 was transfected into HUVECs and 786-0 cells, and the expression level of VASH1 protein was examined by western blotting. Cell proliferation was detected by MTT assay, and cell cycle and apoptosis of HUVECs and 786-0 cells were analyzed by flow cytometry. The invasive ability of 786-0 cells was tested by Transwell assay. Finally, nude mouse models were established to evaluate the therapeutic effect of VASH1. The pReceiver-M61-VASH1 effectively induced the expression of VASH1 in HUVECs and 786-0 cells. VASH1 overexpression effectively inhibited cell proliferation, arrested the cell cycle in the G0/G1 phase and promoted cell apoptosis of HUVECs and 786-0 cells. VASH1 overexpression effectively inhibited the subcutaneous growth of 786-0 tumors in vivo. Therefore, VASH1 is a potential molecular-targeted therapy for patients with RCC.

The incidence of bladder cancer (BLCA) in men is higher than that of women. Differences in androgen levels between men and women are considered the main causes of incidence rate differences. In this study, dihydrotestosterone (DHT) could significantly increase cell proliferation and invasion of BLCA cell line. In addition, BLCA formation and metastatic rates were higher in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) treated male mice than in female and castrated male mice in vivo. However, immunohistochemistry showed that androgen receptor (AR) was found low expressed in normal and BLCA cancer tissues of men and women. Here, a non-AR combination pathway of androgen that promoted BLCA development was investigated. The protein EPPK1 was bombinated with DHT determined by biotinylated DHT-binding pull-down experiments. EPPK1 was highly expressed in BLCA tissues, and EPPK1 knockdown significantly inhibited BLCA cell proliferation and invasion promoted by DHT. Moreover, JUP expression was elevated in DHT-treated high-EPPK1 expression cells, and JUP knockdown inhibited cell proliferation, and invasion. EPPK1 over-expression could increase tumor growth in nude mice and JUP expression. Furthermore, DHT increased the expression of MAPK signals p38, p-p38, and c-Jun expression, and c-Jun could combine with the JUP promoter. However, no functions in EPPK1 knockdown cells and p38 inhibitor could suppress the DHT-treated increase, indicating that p38 MAPK may be involved in the regulation of DHT-dependent EPPK1-JUP-promoting BLCA cell proliferation and invasion. The growth of bladder tumors in BBN-treated wild mice was inhibited by the addition of the hormone inhibitor Goserelin. Our findings indicated the potential oncogenic role and mechanism of DHT in BLCA pathogenesis through a non-AR pathway, which may serve as a novel therapeutic target for BLCA. Androgen inhibitors may be used as endocrine therapy for bladder cancer.

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