Declined circular RNA mitofusin 2 constrains the deterioration of Wilms tumor via modulating microRNA-372-3p/transforming growth factor-ß receptor type 2 axis.

To explore the action and mechanism in which circular RNA (circRNA) mitofusin 2 (MFN2) repressed the malignant proliferation of Wilms tumor (WT) via modulating microRNA (miR)-372-3p/transforming growth factor-ß receptor type 2 (TGFBR2) axis. CircRNA MFN2 was distinctly elevated in the tissues and cells of WT patients, while miR-372-3p was silenced in the tissues and cells of WT. Test of TGFBR2, PCNA and Bax was implemented. Transfection with si-circRNA MFN2 or miR-372-3p-mimic restrained cancer cell advancement and the number of PCNA content was declined, while transfection with miR-372-3p-inhibitor was opposite, and PCNA content was augmented. MiR-372-3p-inhibitor turned around si-circRNA MFN2's therapeutic action after co-transfection with si-circRNA MFN2 + miR-372-3p-inhibitor. Ultimately, it was verified that circRNA MFN2 was negatively associated with miR-372-3p, which was negatively linked with TGFBR2, and circRNA MFN2 was positively associated with TGFBR2. To sum up, the results of this research illuminated circRNA MFN2 repressed WT's malignant proliferation via modulating miR-372-3p/TGFBR2 axis.

Activation of UPR Signaling Pathway is Associated With the Malignant Progression and Poor Prognosis in Prostate Cancer.

BACKGROUND: Currently, the role of UPR signaling in prostate cancer (PCa) is unclear. To evaluate the relationship between UPR signaling pathway and the prognosis of PCa, we explored the expression of IRE1, PERK, and ATF6 in tissues. METHODS: A total of 160 PCa and 30 benign prostate hyperplasia (BPH) tissues were collected. The expression of UPR signaling factors was assessed by immunohistochemistry. The staining characteristics were identified and evaluated for associations with clinicopathologic parameters, PSA recurrence survival, and prostate cancer-specific morality. RESULTS: The expressions of ATF6α, PERK, and IRE1α were significantly associated with Gleason grade, PSA level, T stages and M stage, while this association was not significant in N stage. Additionally, UPR signaling factors expressed correlatively with each other. In further studies, high expression level of UPR signaling factors was usually detected in patients who suffered poor prognosis. Patients with positive UPR signaling factors meet shorter survival duration both on cancer-specific morality and PSA recurrence. Multivariate analysis showed that IRE1α (HR = 4.461 95%CI = 1.270-15.670 P = 0.020) could be a potential factor in predicting PSA recurrence independently. CONCLUSIONS: UPR signaling factors were co-activated and activation of UPR signaling was implicated to the malignant progression and worse prognosis of PCa. The mechanism and function of UPR signaling in PCa are still to be determined. Prostate 77:274-281, 2017. © 2016 Wiley Periodicals, Inc.

Rce1 expression in renal cell carcinoma and its regulatory effect on 786-O cell apoptosis through endoplasmic reticulum stress.

Ras and a-factor-converting enzyme 1 (Rce1) is located in the endoplasmic reticulum (ER) and is thought to be responsible for endoproteolytic processing of the vast majority of CAAX proteins. Endoplasmic reticulum stress (ERS) plays an important role in renal cell carcinoma (RCC); however, the expression and role of Rce1 in RCC have not been extensively studied. We aimed to investigate the expression of Rce1 in RCC tissues and its molecular mechanism in ERS-induced apoptosis in RCC 786-O cells. We first used western blotting, quantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry to detect the Rce1 expression in renal carcinoma tissues and paracancerous tissues. It was found that Rce1 expression was upregulated in RCC tissues, and its positive expression level was strongly associated with clinicopathologic features. Next, we detected the expression of Rce1 in human embryonic kidney cell line HEK293 and human renal carcinoma cell lines 786-O, ACHN, and A498. Higher expression of Rce1 was found in human renal carcinoma cell lines, especially in 786-O cells. Knockdown of Rce1 in 786-O cells increased apoptosis and inhibited proliferation (P < 0.05). Moreover, downregulation of Rce1 upregulated the expression of the pro-apoptotic protein Bax, but downregulated the expression of the anti-apoptotic protein Bcl-2. Further studies showed that downregulation of Rce1 also affected the expression of ERS factors. In conclusion, our results indicated that Rce1 plays a key role in RCC. Low expression of Rce1 might indirectly increase apoptosis and inhibit proliferation of renal carcinoma cells through ERS.

Systemic metastases in large cell neuroendocrine prostate cancer: a rare case report and literature review.

Neuroendocrine prostate neoplasms, encompassing small cell carcinoma, carcinoid, and large cell carcinoma, are infrequently observed in malignant prostate tumors. The occurrence of large cell neuroendocrine prostate cancer (LCNEPC) is exceedingly rare. In this study, the patient initially presented with a persistent dysuria for a duration of one year, accompanied by a serum prostate-specific antigen (PSA) level of 17.83ng/mL. Prostate magnetic resonance imaging (MRI) and chest computed tomography (CT) scan showed that a neoplastic lesion was considered, and prostate biopsy confirmed prostate adenocarcinoma with a Gleason score of 7 (4 + 3). Then, thoracoscopic lung tumor resection was performed, and the pathological examination revealed the presence of primary moderately differentiated invasive adenocarcinoma of the lung and metastatic prostate adenocarcinoma, the Gleason score was 8 (4 + 4). After 1 year of endocrine therapy with goserelin acetate and bicalutamide, he underwent a laparoscopic radical prostatectomy (LRP), the pathological report indicated the presence of adenocarcinoma mixed with NE carcinoma. Two months after the LRP, the patient experienced gross hematuria and sacral tail pain. Further examination revealed multiple metastatic lesions throughout the body. He also underwent transurethral resection of bladder tumor (TURBT) for bladder tumor and received etoposide+ cisplatin chemotherapy three weeks post-surgery. The patient eventually died of multi-organ failure due to myelosuppression after chemotherapy. This case report presents an uncommon instance of LCNEPC with widespread systemic metastases, while also providing a comprehensive review of existing literature to facilitate improved management and treatment strategies for similar patients in subsequent cases.

Expression and Role of TRIM2 in Human Diseases.

Tripartite motif (TRIM) protein family proteins contain more than 80 members in humans, and most of these proteins exhibit E3 ubiquitin ligase activity mediated through a RING finger domain. Their biological functions are very complex, and they perform diverse functions in cell evolution processes, such as intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy, and carcinogenesis. Tripartite motif-containing protein 2 (TRIM2), a member of the TRIM superfamily, is an 81 kDa multidomain protein, also known as CMT2R or RNF86, located at 4q31.3. TRIM2 functions as an E3 ubiquitin ligase. Current studies have shown that TRIM2 can play roles in neuroprotection, neuronal rapid ischemic tolerance, antiviral responses, neurological diseases, etc. Moreover, based on some studies in tumors, TRIM2 regulates tumor proliferation, migration, invasion, apoptosis, and drug resistance through different mechanisms and plays a critical role in tumor occurrence and development. This review is aimed at providing a systematic and comprehensive summary of research on TRIM2 and at exploring the potential role of TRIM2 as a biomarker and therapeutic target in many kinds of human diseases.

Overexpressed Rce1 is positively correlated with tumor progression and predicts poor prognosis in prostate cancer.

Ras and a-factor-converting enzyme 1 (Rce1) have been reported to play a key role in the proteolysis processing of Ras proteins. The present study investigated the prognostic significance of Rce1 in patients with prostate cancer (PCa). The expressions of the mRNA and protein of Rce1 were analyzed in 12 pairs of PCa and benign prostatic hyperplasia (BPH) by quantitative real-time polymerase chain reaction and Western blotting, respectively. Immunohistochemistry was used to examine expression of Rce1 protein in 74 PCa tissues and 30 BPH tissues. The association between Rce1 expression and the specific clinicopathologic features was evaluated by χ(2) tests. Kaplan-Meier and Cox proportional hazards regression models were used to analyze the data. We found that expression of Rce1 mRNA and protein was markedly higher in PCa tissues than in paired BPH tissues. Expression of Rce1 in PCa was strongly associated with clinicopathologic features. It was detected in 69 (93.24%) of 74 PCa tissues by immunohistochemistry, and it was found to be associated with Gleason score (P = .013), T class (P = .015), and distant metastasis (P = .044). Patients with PCa having higher Rce1 expression had substantially shorter survival times than patients with lower Rce1 expression. Univariate and multivariate analysis revealed that Rce1 was an independent prognostic factor. In conclusion, our study suggests that expression of Rce1 can serve as an independent biomarker for the prognosis of PCa patients.