In this study, we aimed to investigate the effects of lncRNA CASC11 on gastric cancer (GC) cell progression through regulating miR-340-5p and cell cycle pathway. Expressions of lncRNA CASC11 in gastric cancer tissues and cell lines were determined by qRT-PCR. Differentially expressed lncRNAs, mRNAs and miRNAs were screened through microarray analysis. The relationship among CASC11, CDK1 and miR-340-5p was predicted by TargetScan and validated through dual luciferase reporter assay. Western blot assay examined the protein level of CDK1 and several cell cycle regulatory proteins. GO functional analysis and KEGG pathway analysis were used to predict the association between functions and related pathways. Cell proliferation was determined by CCK-8 assays. Cell apoptosis and cell cycle were detected by flow cytometry assay. CASC11 was highly expressed in GC tissues and cell lines. Knockdown of CASC11 inhibited GC cell proliferation, promoted cell apoptosis and blocked cell cycle. KEGG further indicated an enriched cell cycle pathway involving CDK1. QRT-PCR showed that miR-340-5p was down-regulated in GC cells tissues, while CDK1 was up-regulated. Furthermore, CASC11 acted as a sponge of miR-340-5p which directly targeted CDK1. Meanwhile, miR-340-5p overexpression promoted GC cell apoptosis and induced cell cycle arrest, while CDK1 overexpression inhibited cell apoptosis and accelerated cell cycle. Our study revealed the mechanism of CASC11/miR-340-5p/CDK1 network in GC cell line, and suggested that CASC11 was a novel facilitator that exerted a biological effect by activating the cell cycle signaling pathway. This finding provides a potential therapeutic target for GC.
Objectives:The role of p62 in cancer is controversial. Evidence has shown that p62 is upregulated in different cancers and promotes tumour growth, such as in liver cancer and lung cancer. However, a recent study showed that the downregulation of p62 in hepatic stellate cells (HSCs) promotes hepatocellular carcinoma (HCC) development.How p62 is regulated in colorectal cancer (CRC) remains largely unknown. In this study, we aimed to investigate the roles and molecular mechanisms of p62 in CRC.
Materials and Methods:The expression levels of p62 in CRC tissues and adjacent non-tumour tissues were determined by immunohistochemistry (IHC). Stable p62overexpression HCT116 cells and p62-knockdown SW480 cells were established with lentiviral vectors. The role of p62 in CRC was investigated in in vitro and in vivo functional studies. The relationship between p62 and the vitamin D receptor (VDR) was investigated by coimmunoprecipitation (Co-IP) assays.Results: p62 was significantly upregulated in CRC, and a high p62 level was an independent risk factor for a poor prognosis in CRC patients. p62 promoted CRC migration and invasion by inhibiting apoptosis and promoting cell proliferation in vitro, and p62 aggravated tumour growth and metastasis in vivo. Co-IP assays indicated that p62 interacts with the VDR and may target the NRF2-NQO1 axis.
Conclusions:Our study suggested that p62 functions as an oncogene in CRC through inhibiting apoptosis and promoting cell proliferation by interacting with the VDR.
BackgroundThere is lack of clinical evidence supporting the value of the Kyoto classification of gastritis for the diagnosis of Helicobacter pylori (H. pylori) infection in Chinese patients, and there aren’t enough specific features for the endoscopic diagnosis of past infections, which is of special significance for the prevention of early gastric cancer (GC).MethodsThis was a prospective and multicenter study with 650 Chinese patients. The H. pylori status and gastric mucosal features, including 17 characteristics based on the Kyoto classification and two newly-defined features unclear atrophy boundary (UAB) and RAC reappearance in atrophic mucosa (RAC reappearance) were recorded in a blind fashion. The clinical characteristics of the subjects were analyzed, and the diagnostic odds ratio (DOR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristics curve (ROC/AUC), and 95% confidence intervals were calculated for the different features, individually, and in combination.ResultsFor past infection, the DOR of UAB was 7.69 (95%CI:3.11−19.1), second only to map-like redness (7.78 (95%CI: 3.43−17.7)). RAC reappearance showed the highest ROC/AUC (0.583). In cases in which at least one of these three specific features of past infection was considered positive, the ROC/AUC reached 0.643. For current infection, nodularity showed the highest DOR (11.7 (95%CI: 2.65−51.2)), followed by diffuse redness (10.5 (95%CI: 4.87−22.6)). Mucosal swelling showed the highest ROC/AUC (0.726). Regular arrangement of collecting venules (RAC) was specific for no infection.ConclusionsThis study provides evidence of the clinical accuracy and robustness of the Kyoto classification of gastritis for the diagnosis of H. pylori in Chinese patients, and confirms UAB and RAC reappearance partly supplement it for the diagnosis of past infections, which is of great benefit to the early prevention of GC.
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