Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1.

BACKGROUND: Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms. METHODS: Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). RESULTS: It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. CONCLUSION: Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.

Chinese and global burdens of gastric cancer from 1990 to 2019.

BACKGROUND: Gastric cancer is a common cancer in China. This project investigated the disease burden of gastric cancer from 1990 to 2019 in China and globally. METHODS: The global age-standardized rates (ASRs) were extracted from the Global Burden of Disease. Moreover, the estimated annual percentage changes (eAPCs) in the ASRs of incidence (ASIR), mortality (ASMR), and disability-adjusted life-years (DALYs) were calculated to determine the trends by countries and regions. RESULTS: In China, the ASIR declined from 37.56 to 30.64 per 100,000 and the ASMR declined from 37.73 to 21.72 per 100,000. The global ASIR decreased from 22.44 to 15.59 and the ASMR declined from 20.48 to 11.88 per 100,000 persons from 1990 to 2019. The ASIR was the lowest in Malawi (3.28 per 100,000) and the highest in Mongolia (43.7 per 100,000), whereas the ASMR was the lowest in the United States of America (3.40 per 100,000) and the highest in Mongolia (40.04 per 100,000) in 2019. The incidence of early-onset gastric cancer increased in China. The DALYs attributed to gastric cancer presented a slight decrease during the period. China had a higher mortality/incidence ratio (0.845) and 5-year prevalence (27.6/100,000) than most developed countries. CONCLUSION: China presented a steady decline in the incidence and mortality rates for gastric cancer. The global ASIR, ASMR, and DALYs showed a slight rise decrease. Different patterns of gastric cancer rates and temporal trends have been identified in different geographical regions, indicating that specific strategies are needed to prevent the increase in some countries.

IL-36ß promotes anti-tumor effects in CD8+ T cells by downregulating micro-RNA let-7c-5p.

BACKGROUND: The anti-tumor effect of interleukin (IL)-36ß-mediated activation of CD8+ T cells has been reported, but the molecular mechanism is largely undefined. METHODS: The levels of IL-36ß in pancreatic cancer were examined by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. Cytology and animal experiments were performed to study the effects of IL-36ß on the growth of pancreatic cancer cells. We then examined the changes of CD8+ T cells and natural killer (NK) cells in the tumor by flow cytometry. The microRNA expression profiles were determined by microarray analysis. RESULTS: The results revealed decreased levels of IL-36ß in pancreatic cancer tissues. In addition, IL-36ß inhibited tumor growth and promoted CD8+ T and NK cell proliferation in the tumor microenvironment (TME). Moreover, IL-36ß stimulated CD8+ T cells to synthesize high amounts of interferon-gamma (IFN-γ) and IL-2. Microarray analysis showed that IL-36ß administration to human and mouse CD8+ T cells consistently downregulated the miRNA, let-7c-5p. Downregulation of let-7c-5p resulted in IFN-γ and IL-2 upregulation in CD8+ T cells, whereas its upregulation had the opposite effect. Further experiments demonstrated that IL-36ß downregulated IFN-γ in let-7c-5p+ CD8+ T cells. CONCLUSIONS: These findings suggest IL-36ß promotes IFN-γ and IL-2 production in CD8+ T cells, as well as anti-tumor effects in CD8+ T cells by downregulating let-7c-5p.

Type IV choledochal cyst with polycystic kidney disease: a case report.

BACKGROUND: Choledochal cysts are divided into 5 types. Physicians believe that Caroli disease (which refers to type V biliary cysts) is a special type of biliary cyst caused by a mutation in the PKHD1 gene and is associated with autosomal recessive polycystic kidney disease (ARPKD). There is currently no clear association between other types of choledochal cysts and polycystic kidney disease. CASE PRESENTATION: We report a 65-year-old male patient with jaundice, decreased appetite, and itchy skin. His biochemistry test results indicated obstructive jaundice disease. Cross-sectional imaging showed a type IVA choledochal cyst accompanied by autosomal dominant polycystic kidney disease (ADPKD). Due to economic difficulties, the patient achieved percutaneous transhepatic cholangial drainage (PTCD) instead of surgery. CONCLUSION: To our knowledge, this is the second case report of the coexistence of type IVA choledochal cysts and ADPKD. We conclude that it is vital to be aware that the above condition is a possibility. This case report will aid earlier diagnosis and management and possibly prevent further damage to liver and kidney function.

A multicenter retrospective study of endoscopic submucosal tunnel dissection for large lesser gastric curvature superficial neoplasms.

BACKGROUND AND AIM: Endoscopic submucosal tunnel dissection (ESTD) has been used for dissection of esophageal and gastric lesions. However, outcomes of ESTD for large lesions in the lesser gastric curvature had not been acknowledged because previous reports had the limitations of being single-center studies. We aimed to clarify the outcomes of ESTD for large lesser gastric curvature superficial neoplasms and provide our experience to accelerate its application. METHODS: Between July 2014 and July 2016, 87 patients with early cancer in the lesser gastric curvature treated at six Chinese institutions were enrolled. Our primary outcome was dissection speed. Moreover, both efficacy and safety clinical data were collected and analyzed retrospectively. RESULTS: All of the 87 patients were found to successfully undergo ESTD or ESD. Of these, 32 underwent ESTD and 55 underwent endoscopic submucosal dissection (ESD). The ESTD group had a higher dissection speed (18.0 mm2/min vs. 7.8 mm2/min, p < 0.01) and was associated with higher en bloc resection rate (100% vs. 87.3%, p = 0.035) and curative resection rate (100% vs. 85.5%, p = 0.024) compared with the ESD group. No perforation or muscular injury occurred in the ESTD group and its intraprocedural bleeding rate was lower (59.4% vs. 100%, p < 0.01) than that of the ESD group. CONCLUSIONS: In this multicenter retrospective study, outcomes of ESTD were excellent with a higher dissection speed and radical curative rate compared with ESD.

Inactivation of BLU is associated with methylation of Sp1-binding site of BLU promoter in gastric cancer.

BLU is a candidate tumor suppressor gene, which is epigenetically inactivated in many human malignancies. However, the expression and biological functions of BLU in gastric cancer has not yet been reported. In the present study, we identified a functional BLU promoter which was regulated by the transcription activator Sp1. Bisulfite sequencing and qRT-PCR assays indicated that the silence of BLU expression in gastric cancer was significantly associated with DNA hypermethylation of BLU promoter including -39 CpG site located in the Sp1 transcription element. The expression of BLU was notably restored in AGS and SGC7901 cells following the demethylation-treatment with 5'-Aza-2'-deoxycytidine. Moreover, the results from ChIP, EMSA and luciferase reporter gene showed that -39 CpG methylation could prevent Sp1 from binding to the promoter of BLU and decreased transcription activity of the BLU gene by ~70%. In addition, knockdown of BLU significantly promoted cellular proliferation and colony formation in gastric cancer cells. In conclusion, we identified a novel functional BLU promoter and proved that BLU promoter activity was regulated by Sp1. Furthermore, we found that hypermethylated -39 CpG in BLU proximal promoter directly reduced its binding with Sp1, which may be one of the mechanisms accounting for the inactivation of BLU in gastric cancer.