Hydrogel-based miR-192 delivery inhibits the development of hepatocellular carcinoma by suppressing the GSK3ß/Wnt/ß-catenin pathway.

Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by high invasiveness, metastasis, and poor prognosis, which lacks effective treatments. Although the role of miR-192 in HCC development has been recognized, the underlying molecular mechanism is still poorly understood. This study aimed to explore the impact of mir-192 on HCC and its potential as a therapeutic strategy. Wound healing assay, Transwell assay, CCK-8 assay, and flow cytometry were performed to detect the impact of miR-192 on HCC cell metastasis, invasion, proliferation, and apoptosis, respectively. q-PCR and western blot were applied to measure the relative mRNA and protein expression of the GSK3ß/Wnt/ß-catenin pathway in miR-192-overexpressing cell lines. Immunofluorescence was carried out to detect the nuclear translocation of ß-catenin. starBase website and dual luciferase reporter assay were used to verify the interaction between miR-192 and the target gene WNT10B 3'-untranslated region (3'-UTR) of the Wnt pathway. In addition, we developed algin/polyethyleneimine@miR-192 (AG/PEI@miR-192) nanohydrogel for in vivo delivery of miR-192-agomir. The results revealed that overexpressed miR-192 reduced the expression of HCC cell surface markers CD90, EpCAM, and CD133. Moreover, miR-192 overexpression inhibited HCC cell metastasis, invasion, and proliferation, promoted cell apoptosis, and reduced GSK3ß/Wnt/ß-catenin pathway expression. Additionally, AG/PEI@miR-192 exhibited good drug release and tumor inhibition. In conclusion, our study suggested that miR-192 inhibits HCC development by suppressing the GSK3ß/Wnt/ß-catenin pathway and proposed a promising hydrogel-based miR-192 delivery approach to hinder tumor growth.

TRIM50 Inhibits Proliferation and Metastasis of Gastric Cancer via Promoting ß-Catenin Degradation.

Background: Gastric cancer (GC) is a common malignancy with a poor prognosis. Tripartite motif-containing 50 (TRIM50) belongs to the TRIM family and is reported to be related to numerous cancers. This study aimed to investigate the function of TRIM50 in GC. Methods: Three microarray datasets (GSE13911, GSE79973, and GSE19826) containing GC and adjacent nontumor tissues were used for bioinformatics analysis to screen GC-related genes and assess the associations between GC development and TRIM50 expression. Then, TRIM50 expression in GC cells was detected at mRNA and protein levels. After TRIM50 was knockdown or overexpressed, the effect of TRIM50 on the proliferation and metastasis of GC cells was analyzed using Cell Counting Kit-8 (CCK-8), flow cytometry, scratch, and Transwell assays. The interaction between TRIM50 and ß-catenin was analyzed. The expression of cell cycle-, migration-, invasion-, and Wnt/ß-catenin signaling pathway-related proteins was detected by Western blot. Furthermore, we measured the role of TRIM50 overexpression on tumor growth as well as the Wnt/ß-catenin signaling pathway in vivo. In addition, XAV939 (a WNT/ß-catenin signaling pathway inhibitor) was used to clarify the mechanism of TRIM50 on GC. Results: Bioinformatics revealed that TRIM50 expression was decreased in GC samples and associated with GC development. In vitro study revealed that TRIM50 overexpression impeded the GC cell proliferation and metastasis, while TRIM50 knockdown presented the opposite results. In addition, TRIM50 interacted with ß-catenin to induce the degradation of ß-catenin. In in vivo assay, TRIM50 overexpression inhibited tumor growth and blocked the Wnt/ß-catenin signaling pathway. In addition, TRIM50 knockdown-promoted cell proliferation and metastasis in GC cells were inverted by XAV939. Conclusion: TRIM50 overexpression may inhibit cell proliferation and metastasis in GC via ß-catenin degradation, indicating that TRIM50 could be a target for the treatment of GC.

LncRNA ASB16-AS1 drives proliferation, migration, and invasion of colorectal cancer cells through regulating miR-185-5p/TEAD1 axis.

As a common malignant tumor, colorectal cancer (CRC) has a high incidence. Recent investigations have suggested that although great improvement has been achieved in the survival rate of early-stage CRC patients, the overall survival rate remains low. Mounting reports have proved that lncRNAs take part in the development of various cancers and possess the regulatory functions in cancers. For example, ASB16 antisense RNA 1 (ASB16-AS1) is a poorly researched novel lncRNA whose specific functions in CRC are still unknown. In our research, we discovered that ASB16-AS1 was with high expression in CRC cells. In addition, ASB16-AS1 silencing restrained the proliferation, migration, invasion, and stemness while accelerating cell apoptosis of CRC cells. Mechanism experiments were applied to explore the regulatory mechanism of ASB16-AS1. It turned out that miR-185-5p could interact with ASB16-AS1 and inhibited the progression of CRC cells. TEAD1 (TEA domain transcription factor1) - a major effector of the Hippo signaling was proved to serve as the target of miR-185-5p and promote CRC development. In short, ASB16-AS1 drove the progression of CRC through the regulation of miR-185-5p/TEAD1 axis.

Knockdown of ZNF479 inhibits proliferation and glycolysis of gastric cancer cells through regulating ß-catenin/c-Myc signaling pathway.

Gastric cancer is the fifth most common malignancy and the third most deadly tumor in the world. Zinc finger protein 479 (ZNF479) has been demonstrated to play crucial roles in hepatocellular carcinoma. However, the function of ZNF479 in gastric cancer remains to be clarified. The current study aimed to investigate the role of ZNF479 in gastric cancer progression and elucidate the potential molecular mechanism. In this study, Cell Count Kit-8 and colony formation assays demonstrated that knockdown of ZNF479 inhibited cell proliferation in AGS and SGC-7901 cells. Of note, knockdown of ZNF479 hinders tumor growth of xenograft tumor mice. What is more, knockdown of ZNF479 inhibited glucose uptake, lactate production, adenosine triphosphate level, and extracellular acidification ratio; increased oxygen consumption ratio in gastric cancer cells; and decreased the expression of glycolytic proteins both in vitro and in vivo. Furthermore, analysis mechanism suggests that ZNF479 participated in the regulation of gastric cancer progression through affecting the ß-catenin/c-Myc signaling pathway. Collectively, ZNF479 plays a role as an oncogene through modulating ß-catenin/c-Myc signaling pathway in the development of gastric cancer, which provides a new research target for future studies.

Is tailored therapy based on antibiotic susceptibility effective ? a multicenter, open-label, randomized trial.

An effective eradication therapy of Helicobacter pylori (H. pylori) should be used for the first time. In this study, we assessed whether tailored therapy based on antibiotic susceptibility testing is more effective than traditional therapy. We also evaluated the factors that cause treatment failure in high-resistance areas. For this multicenter trial, we recruited 467 H. pylori-positive patients. The patients were randomly assigned to receive tailored triple therapy (TATT), tailored bismuth-containing quadruple therapy (TABQT), or traditional bismuth-containing quadruple therapy (TRBQT). For the TATT and TABQT groups, antibiotic selection proceeded via susceptibility testing using an agar-dilution test. The patients in the TRBQT group were given amoxicillin, clarithromycin, esomeprazole, and bismuth. Successful eradication was defined as a negative 13C-urea breath test at least eight weeks after the treatment ended. Susceptibility testing was conducted using an agar-dilution test. The eradication rate was examined via intention-to-treat (ITT) and per-protocol (PP) analyses. The clarithromycin, levofloxacin, and metronidazole resistance rates were 26.12%, 28.69%, and 96.79%, respectively. Resistance against amoxicillin and furazolidone was rare. The eradication rates for TATT, TRBQT, and TABQT were 67.32%, 63.69%, and 85.99% in the ITT analysis (P 0.001) and 74.64%, 68.49%, and 91.22% in the PP analysis (P 0.001), respectively. The efficacy of TABQT was affected by clarithromycin resistance, and bismuth exerted a direct influence on TATT failure. TABQT was the most efficacious regimen for use in high-resistance regions, especially among clarithromycin-susceptible patients.

Centralized isolation of Helicobacter pylori from multiple centers and transport condition influences.

AIM: To evaluate the efficacy of centralized culture and possible influencing factors. METHODS: From January 2010 to July 2012, 66452 patients with suspected Helicobacter pylori (H. pylori) infection from 26 hospitals in Zhejiang and Jiangsu Provinces in China underwent gastrointestinal endoscopy. Gastric mucosal biopsies were taken from the antrum for culture. These biopsies were transported under natural environmental temperature to the central laboratory in Hangzhou city and divided into three groups based on their transport time: 5, 24 and 48 h. The culture results were reported after 72 h and the positive culture rates were analyzed by a χ (2) test. An additional 5736 biopsies from H. pylori-positive patients (5646 rapid urease test-positive and 90 (14)C-urease breath test-positive) were also cultured for quality control in the central laboratory setting. RESULTS: The positive culture rate was 31.66% (21036/66452) for the patient samples and 71.72% (4114/5736) for the H. pylori-positive quality control specimens. In the 5 h transport group, the positive culture rate was 30.99% (3865/12471), and 32.84% (14960/45553) in the 24 h transport group. In contrast, the positive culture rate declined significantly in the 48 h transport group (26.25%; P < 0.001). During transportation, the average natural temperature increased from 4.67 to 29.14 °C, while the positive culture rate declined from 36.67% (1462/3987) to 24.12% (1799/7459). When the temperature exceeded 24 °C, the positive culture rate decreased significantly, especially in the 48 h transport group (23.17%). CONCLUSION: Transportation of specimens within 24 h and below 24 °C is reasonable and acceptable for centralized culture of multicenter H. pylori samples.

Antibiotic resistance of Helicobacter pylori isolated in the Southeast Coastal Region of China.

BACKGROUND: The resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide, lowering its efficacy in current eradication therapies. This study evaluated H. pylori resistance to antibiotics in the southeast coastal region of China and suggests appropriate alternatives. MATERIALS AND METHODS: Seventeen thousand seven hundred and thirty one H. pylori strains were collected from eight areas of two provinces in coastal southeast China from 2010 to 2012. The resistance of these strains to six antibiotics was tested using the agar dilution method. RESULTS: The resistance rates to clarithromycin, metronidazole, levofloxacin, amoxicillin, gentamicin and furazolidone were 21.5, 95.4, 20.6, 0.1, 0.1 and 0.1%, respectively. Double, triple and quadruple antibacterial resistant percentages were 25.5, 7.5 and 0.1%, respectively. A positive association between the resistance to levofloxacin and to clarithromycin was found, but there was a negative correlation in the resistances to levofloxacin and to metronidazole. CONCLUSIONS: The prevalence of H. pylori resistance to clarithromycin, metronidazole, levofloxacin and multiple antibiotics in coastal southeast China is high. Choice of therapy should be individualized based on a susceptibility test in this region of the country.