Deltex E3 Ubiquitin Ligase 3L confers radioresistance in prostate cancer via Akt pathway

Purpose: To determine the effect of Deltex E3 Ubiquitin Ligase 3L (DTX3L) on the radioresistance of prostate cancer (PCa).Methods: A PCa cell model of radioresistance was established via exposure of cancer cell lines to fractionated radiation. The MTT {(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)} assay and western blotting were performed to evaluate the impact of DTX3L on cell survival and DNA damage repair. The molecular mechanism of action was evaluated by western blotting.Results: DTX3L was elevated in PCa cell lines compared with normal primary prostate epithelial cells (p < 0.01). The survival of PCa cells exposed to radiation was promoted by overexpression of DTX3L, while knockdown of DTX3L abrogated the radioresistance. Moreover, overexpression of DTX3Ldecreased phosphorylation of histone H2AX (γH2AX) and increased Rad51 levels (p < 0.01). However, knockdown of DTX3L reversed the accumulation of γH2AX and Rad51. Phosphorylation of AKT was promoted by DTX3L overexpression, but was reduced by DTX3L knockdown (p < 0.01). Inhibition of AKT (protein kinase B) counteracted the promotion ability of DTX3L on the radioresistance of PCa cells via decreased cell survival ratio, and also inhibited DNA damage repair via accumulation of γ-H2AX and depletion of Rad51 (p < 0.01).Conclusion: DTX3L increases the resistance of prostate cancer to radiotherapy and DNA damage repair in PCa via AKT pathway, indicating a potential therapeutic strategy to overcome radioresistance in PCa. Keywords: DTX3L (Deltex E3 Ubiquitin Ligase 3L), DNA damage, Phosphorylation, Radioresistance, AKT, Protein kinase B, Prostate cance

Primary squamous cell carcinoma of renal parenchyma: A case report and literature review

RationalePrimary renal parenchymal squamous cell carcinoma (SCC) is an extremely rare tumor that is difficult to diagnose by hematology and imaging studies and is often diagnosed later than other primary renal cancers.DiagnosisA 52-year-old male patient was found to have cysts in both kidneys for 1 week. No urgency and frequency of urination, no dysuria, no gross hematuria, and no significant changes in recent body weight were reported.InterventionsThe upper pole of the right kidney is a cystic and solid mass (8.3 cm * 8.2 cm * 8.1 cm), the cystic part has long T1 and long T2 signals, the solid part has mixed signals, and some parts have limited diffusion. There were nodular long T1 and short T2 calcification signals. An enhanced scan of the solid part showed uneven enhancement and continuous enhancement of the mass capsule. Cystic renal cancer was considered because of the multiple cysts in both kidneys. Surgical treatment was performed. Postoperative pathology revealed well-differentiated squamous cell carcinoma of the right kidney with cystic degeneration, 8.5 cm * 6 cm in size, infiltrating the renal parenchyma, and the cutting edge was negative. The pathological stage was pT2bN0M0.OutcomeAt the follow-up 5 months after the operation, no metastasis was found.ConclusionRenal SCC is rare and easily misdiagnosed and missed. Pathological diagnosis is still the gold standard for its diagnosis. However, with active surgical treatment, the short-term prognosis of the patient is good

The Diagnostic and Therapeutic Role of Circular RNA HIPK3 in Human Diseases

Circular RNAs (circRNAs) are a class of noncoding RNAs with closed-loop of single-stranded RNA structure. Although most of the circRNAs do not directly encode proteins, emerging evidence suggests that circRNAs play a pivotal and complex role in multiple biological processes by regulating gene expression. As one of the most popular circRNAs, circular homeodomain-interacting protein kinase 3 (circHIPK3) has frequently gained the interest of researchers in recent years. Accumulating studies have demonstrated the significant impacts on the occurrence and development of multiple human diseases including cancers, cardiovascular diseases, diabetes mellitus, inflammatory diseases, and others. The present review aims to provide a detailed description of the functions of circHIPK3 and comprehensively overview the diagnostic and therapeutic value of circHIPK3 in these certain diseases