Search

Xiaoxu Chen,1,2,* Haiyong Ji,3,* Jianwei Wang,4 Guiting Zhao,1,2 Bin Zheng,1,2 Zhihong Niu,1,2 Wei He1,2 1Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 3The Third Department of Surgery, Ningjin People’s Hospital, Dezhou, Shandong, People’s Republic of China; 4Department of Urology, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HeDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of ChinaTel +86 53168776310Email Hewei@bjmu.edu.cnPurpose: Elevated plasma D-dimer levels were thought to be associated with decreasing survival in various cancers. The relationship between plasma D-dimer levels and clinicopathology and the optimal D-dimer cutoff as a prognostic predictor has not been determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the prognostic value of preoperative plasma D-dimer levels as a predictor of patient outcomes in UTUC following radical nephroureterectomy.Patients and Methods: We retrospectively reviewed data for 232 patients. The D-dimer cutoff value was set at 0.36 mg/L, and we used the Kaplan–Meier method and Cox’s proportional hazards regression models to analyze the association between D-dimer levels and oncological outcomes. Multivariate Cox regression was used to develop a nomogram, which we evaluated for accuracy using a receiver operating characteristic curve, calibration plot, and decision curve analysis.Results: Plasma D-dimer levels ≥ 0.36 mg/L were significantly associated with advanced tumor status regarding size, location, hydronephrosis, tumor grade, lymph node involvement, grade, and stage (all p < 0.05). The Kaplan–Meier analysis showed that plasma D-dimer levels ≥ 0.36 mg/L predicted worse oncological outcomes vs levels < 0.36 mg/L (all p < 0.001). Univariate and multivariate analyses showed that elevated preoperative plasma D-dimer level was an independent predictor of recurrence-free survival (hazard ratio (HR): 1.67, 95% confidence interval (CI): 1.07– 2.63; p = 0.025), cancer-specific survival (HR: 2.34, 95% CI: 1.30– 4.19; p = 0.004), and overall survival (HR: 1.98, 95% CI: 1.18– 3.34; p = 0.010). We also developed a nomogram predicting 3- and 5-year overall survival probability.Conclusion: D-dimer levels may be a useful prognostic predictor of survival and improve risk stratification and precisely individualize treatment for patients with UTUC.Keywords: urothelial carcinoma, upper urinary tract, prognosis, predictors, D-dimer, nomogram

Guanghui Li,* Xi Wang,* Chunmei Li,* Shuang Hu, Zhixing Niu, Qiang Sun, Minglei Sun Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiang Sun; Minglei SunDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou, Henan 450052, People’s Republic of ChinaTel +86-371 6691 3345Fax +86-371-6691 3935Email qiangsunoral@gmail.com; Dr.mingleisun@gmail.comBackground: Piwi-interacting RNAs (piRNAs) are thought to silence transposable genetic elements. However, the functional roles of piRNAs in oral squamous cell carcinoma (OSCC) remain unelucidated. In the present study, we aimed to investigate the role of Piwi-interacting RNA 1037 (piR-1037) in chemoresistance to cisplatin (CDDP)-based chemotherapy and the oncogenic role of piR-1037 in OSCC cells.Methods: RT-PCR was used to evaluate the levels of piR-1037 and X-linked Inhibitor of apoptosis protein (XIAP) mRNA in OSCC cell lines or tumor xenografts. Transfection of piR-1037 DNA antisense and piR-1037 RNA oligonucleotides was performed to suppress and overexpress piR-1037 in OSCC cells, respectively. A CCK8 assay was used to measure the viability or proliferation of OSCC cells. Apoptosis in OSCC cells and xenografts was determined using a TUNEL assay kit. The activity of caspase-3, caspase-8 and caspase-1 in OSCC cells was measured with colorimetric caspase assay kits. Western blot analysis was conducted to analyze XIAP expression in OSCC cells and xenograft samples. Immunoprecipitation (IP) and RNA pull-down assays were utilized to analyze the piR-1037 - XIAP interaction. Transwell assays were performed to evaluate migration and invasion of OSCC cells.Results: CDDP treatment upregulated piR-1037 expression in OSCC cells and OSCC xenografts. Suppression of the CDDP-induced upregulation of piR-1037 expression enhanced the sensitivity of OSCC cells to CDDP. piR-1037 promoted protein expression and directly bound XIAP, a key apoptotic inhibitor that is implicated in chemoresistance. The relationship between piR-1037 and XIAP suggested that piR-1037 enhanced OSCC cell chemoresistance to CDDP at least partially through XIAP. Moreover, targeting the basal expression of piR-1037 inhibited cell motility by affecting epithelial–mesenchymal transition (EMT).Conclusion: piR-1037 enhances the chemoresistance and motility of OSCC cells. piR-1037 promotes chemoresistance by interacting with XIAP and regulates the motility of OSCC cells by driving EMT.Keywords: piwi-interacting RNA 1037, oral squamous cell carcinoma, cisplatin, apoptosis, X-linked inhibitor of apoptosis protein, motility

Wentao Tang,1,* Pingping Xu,1,* Hong Wang,1,* Zhengchuan Niu,1 Dexiang Zhu,1 Qi Lin,1 Liming Tang,2 Li Ren1 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; 2Department of General Surgery, Affiliated Changzhou No 2 People’s Hospital, Nanjing Medical University, Changzhou, China *These authors contributed equally to this work Background: Growing evidence suggests that miR-150 plays an inhibitory role in various types of cancer. However, the function and underlying mechanisms of miR-150 in triple-negative breast cancer (TNBC) remain unknown. Patients and methods: miR-150 expression was detected by qRT-PCR and ISH in TNBC tumor and adjacent normal breast tissues. miR-150 function was analyzed by wound healing and transwell assay in vitro and mouse lung metastasis model in vivo. mRNA microarray, qRT-PCR, western blotting and luciferase assay were used to identify the target gene of miR-150. HMGA2 over-expression plasmid was co-transfected with miR-150 to study the role of miR-150 through regulating HMGA2.Results: We found that miR-150 was down-regulated in TNBC tumor tissues compared to corresponding adjacent, normal breast tissues, and was correlated with decreased lymph-node metastasis. Ectopic expression of miR-150 suppressed TNBC cell migration in vitro and metastasis in vivo. Mechanistic study revealed that miR-150 down-regulates HMGA2 by directly targeting its mRNA. Moreover, the suppression of cell migration caused by miR-150 is relieved by over-expression of HMGA2, suggesting that miR-150 inhibits migration of TNBC cells by down-regulating HMGA2. Conclusion: This work indicates that the miR-150/HMGA2 axis may serve as a treatment marker in TNBC. Keywords: miR-150, HMGA2, triple-negative breast cancer, metastasis

Wentao Tang,* Meiling Ji,* Guodong He,* Liangliang Yang, Zhengchuan Niu, Mi Jian, Ye Wei, Li Ren, Jianmin Xu Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: An increasing number of studies have demonstrated that circular RNAs (circRNAs) can regulate gene expression through interacting with microRNAs. In this study, we analyzed the expression of antisense to CDR1as in colorectal cancer (CRC). CDR1as had a higher expression in CRC tissues compared to adjacent, normal mucosa and was positively associated with tumor size, T stage, lymph node metastasis, and poor overall survival (OS). Downregulation of CDR1as suppressed CRC cell proliferation and invasion and increased microRNA-7 (miR-7) expression. Intriguingly, ectopic expression of miR-7 in CRC cells consistently inhibited proliferation and invasion, and the miR-7 inhibitor was able to rescue the function of CDR1as knockdown. Mechanistic studies demonstrated that CDR1as silencing suppressed EGFR and IGF-1R expression, which could be partially blocked by the miR-7 inhibitor. Finally, positive correlations between CDR1as expression and EGFR and IGF-1R expression were observed in CRC samples. Thus, given the importance of CDR1as in blocking miR-7 and positively regulating EGFR and IGF-1R, dysregulated CDR1as expression may play an important role in CRC progression. Keywords: CDR1as, colorectal cancer, microRNA-7, proliferation