OTUB2 is a deubiquitinating enzyme that contributes to tumor progression. However, the expression of OTUB2 and its prognostic importance in gastric cancer remain unclear. The expression of OTUB2 and KRT80 in GC tissues was investigated using western blotting, qRT-PCR, multiple immunofluorescence staining, and immunohistochemistry. For survival studies, Kaplan–Meier analysis with the log-rank test was used. The role of OTUB2 during GC proliferation was investigated using in vivo and in vitro assays. OTUB2 was found to be overexpressed in GC tissues and to act as an oncogene, which was linked to patients’ poor prognosis. Knockdown of OTUB2 inhibited the proliferative capacity of GC cells in vitro and in vivo, although the proliferative capacity was restored upon re-supplementation with KRT80. OTUB2 mechanically stabilized KRT80 by deubiquitinating and shielding it from proteasome-mediated degradation through Lys-48 and Lys-63. Furthermore, by activating the Akt signaling pathway, OTUB2 and KRT80 facilitated GC proliferation. In summary, OTUB2 regulates KRT80 stability via deubiquitination promoting proliferation in GC via activation of the Akt signaling pathway, implying that OTUB2 could be a novel prognostic marker.
Although therapeutic methods have been developed, gastric cancer (GC) still leads to high rates of mortality and morbidity and is the fourth leading cause of cancer-associated death and the fifth most common cancer worldwide. To understand the factors associated with the prognostic prediction of GC and to discover efficient therapeutic targets, previous studies on tumour pathogenesis have mainly focused on the cancer cells themselves; in recent years, a large number of studies have shown that cancer invasion and metastasis are the results of coevolution between cancer cells and the microenvironment. It seems that studies on the tumour microenvironment could help in prognostic prediction and identify potential targets for treating GC. In this review, we mainly introduce the research progress for prognostic prediction and the immune microenvironment in GC in recent years, focusing on cancer-associated fibroblasts (CAFs), tumour-associated macrophages (TAMs), and tumour-infiltrating lymphocytes (TILs) in GC, and discuss the possibility of new therapeutic targets for GC.
Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is defined by a series of lesions including synovitis, pustulosis, hyperostosis and osteitis. Osteoarticular disorder is one of the main characteristic features of SAPHO syndrome and typically involves the anterior chest wall, Mandibular involvements occurs in 2%-10% of SAPHO patients and are mainly located in the posterior ramus. 1 Currently, there are no guidelines for treatment of such patients; despite its rarity, the interest in mandibular involvement in SAPHO treatment is rising.SAPHO with mandibular osteitis usually arises as obvious swelling and pain in the posterior mandibular body and ramus, 1-3 few patients would present with temporomandibular joint (TMJ) involvement. A study showed that most primary chronic osteomyelitis patients undergo surgery. 3 In our previous study, we found that 7.7%(2/14) of mandibular-involved SAPHO patients underwent unilateral mandible resection. 4 However, due to rarity of such patients and lack of a related study, the impact of such surgery remains unclear.Here, we present a SAPHO patient with mandibular osteitis who underwent a series of mandibular resection surgeries and repeated relapses. This unique combination of events suggests that surgical
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