Long noncoding RNAs (lncRNAs) have emerged as important regulators in the development and progression of gastric cancer (GC). ARHGAP27P1 is a pseudogene-derived lncRNA, and it has been found to be associated with GC in our preliminary study, but this association has not been studied further. Herein, we confirmed that ARHGAP27P1 was significantly downregulated in GC tissues, plasma and cells. Low expression of ARHGAP27P1 was closely associated with advanced TNM stage, increased invasion depth and lymphatic metastasis. Low ARHGAP27P1 expression also predicted a poor prognosis in GC patients. Functionally, overexpression of ARHGAP27P1 inhibited proliferation, invasion, and migration in GC cells, while silencing of ARHGAP27P1 showed the opposite effects. Mechanistic investigations showed that ARHGAP27P1 had a key role in G0/G1 arrest. We further demonstrated that ARHGAP27P1 was associated with Jumonji-domain containing 3 (JMJD3) and that this association was required for the demethylation of H3K27me3, thereby epigenetically activating expression of p15, p16 and p57. Moreover, knockdown of JMJD3, p15, or p16 consistently reversed the inhibitory effects of ARHGAP27P1 in cell proliferation and cell cycle progression. Taken together, these results suggest that lncRNA ARHGAP27P1, as a novel cell cycle regulator, may serve as a potential target for GC prevention and treatment in human GC.
Background: Retroperitoneal infection is a persistent and widespread infectious disease that is difficult to treat. It is usually caused by secondary complications such as inflammation, damage, or perforation of adjacent organs in the retroperitoneal space. Pathogenic bacteria invade the retroperitoneal space through retroperitoneal and interstitial organs, peripheral tissue, and the blood. As a result, infections mostly arise from severe acute pancreatitis, acute colonic diverticulitis, inflammatory bowel disease, kidney abscess, and biliary tract injury. Initially manifested by the presence of lumbago, this disease spreads easily, is persistent, and is often misdiagnosed. Methods: Review and synthesis of pertinent literature and guidelines pertaining to abdominal infection and retroperitoneal infection. Results: Recent data indicate that mortality rates associated with retroperitoneal infection have been increasing annually. Early diagnosis and treatment have been shown to improve the prognosis. In the early stage, infection is insidious and lacks typical symptoms, and is primarily diagnosed with computed tomography (CT). Strategies that control the source of infection, rational use of antibiotic agents, and nutritional interventions are the primary approaches to treat the infections. Emergence of minimally invasive drainage technologies, including the ultrasound/CT-guided puncture and drainage, percutaneous nephroscope puncture and drainage, and drainage using a catheter through an abdominal puncture device (trocar) have shortened the treatment cycle and disease burden. However, current diagnosis and treatment for retroperitoneal infection are not sufficiently effective because some patients do not show typical clinical manifestations. Moreover, sensitivity and specificity of available auxiliary examination methods are not supported by sufficient evidence-based medical research. Additionally, there are no uniform standards on the timing of surgical intervention and treatment options. Therefore, we summarized the progresses on current diagnosis and treatment approaches for retroperitoneal infection.
The long noncoding RNA (lncRNA) DLGAP1-AS2 has recently been characterized as an oncogenic lncRNA in several cancers. However, its biological roles and clinical significance in gastric cancer (GC) remains barely understood. In this study, we performed a systematic analysis of DLGAP1-AS2 expression with data from the TCGA and GEO database as well as our clinic GC samples. In agreement with previous studies, our findings demonstrated that DLGAP1-AS2 was significantly up-regulated in GC and its high expression was associated with poor prognosis, suggesting that DLGAP1-AS2 might be a putative oncogenic lncRNA of GC. Loss of DLGAP1-AS2 restricted cell proliferation, migration, and invasion in GC cell lines. Mechanically, Wnt1 was identified as the downstream target of DLGAP1-AS2 by using bioinformatics analysis coupled with qPCR and Western blot assays. Furthermore, DLGAP1-AS2 was found to directly interact with the transcriptional repressor Six3, and this interaction hampered Six3 binding to the promoter regions of the Wnt1 gene, thereby leading to transcriptional activation of Wnt1. Consequently, GC cells lacking DLGAP1-AS2 showed a decreased Wnt1 expression and weakened Wnt/β-catenin signaling. Further, Six3 silencing could reverse the above effects, highlighting a pivotal role of Six3 in the DLGAP1-AS2-mediated activation of Wnt/β-catenin signaling. Either genetic (Wnt1 knockdown) or pharmacological (LF3) inhibition of Wnt/β-catenin signaling could effectively abolish the activation of Wnt/β-catenin signaling by Six3 depletion, thereby preventing GC cell malignant transformation. Taken together, our results suggest that DLGAP1-AS2 functions as an oncogenic factor by directly interacting with Six3 to relieve its suppression on Wnt1 expression, thereby driving the malignancy of GC. DLGAP1-AS2/Six3/Wnt1/β-catenin signaling axis might serve as a promising diagnostic and therapeutic target for GC.
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