Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the tumor images shown in Fig. 4G and H were strikingly similar to tumor images (albeit oriented differently) which had previously appeared in Fig. 8A in another article published in the journal International Journal of Oncology [Tang B, Li Y, Yuan S, Tomlinson S and He S: Upregulation of the δ opioid receptor in liver cancer promotes liver cancer progression both in vitro and in vivo. Int J Oncol 43: 1281‑1290, 2013], indicating that results which were purported to have been obtained under different experimental conditions had been derived from the same original source. In view of the fact that these data had already appeared in another publication prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 41: 43‑56, 2019; DOI: 10.3892/or.2018.6825].

Deubiquitinating enzymes regulate protein activity and cell homeostasis by removing ubiquitin moieties from various substrates. Ubiquitin carboxyl-terminal hydrolase 22 (USP22) is a member of the deubiquitinating protease family and is associated with the development of several tumor types. A previous study demonstrated that USP22 is highly expressed in liver cancer, and its high expression is associated with resistance to chemotherapy. However, the role of USP22 in hepatitis B virus (HBV)-associated liver cancer has not yet been elucidated. The current study demonstrated that USP22 was highly expressed in the tissues of patients with HBV-associated liver cancer, and its high expression was associated with clinicopathological characteristics, including tumor size, clinical stage and prognosis. Further results indicated that USP22 may regulate the proliferative and apoptotic abilities of HepG2.2.15 cells. Additionally, investigation into the underlying mechanism, using small interfering RNA, revealed that the downregulation of USP22 inhibited proliferation and promoted apoptosis though the phosphoinositide 3-kinase/protein kinase B signaling pathway. Therefore, USP22 has the potential to be used as an independent predictor of patient prognosis, as well as a therapeutic target for the treatment of HBV-associated liver cancer.

Polycomb group family is a class of proteins that have important roles in both physiological and pathological processes, and its family member Chromobox homolog 8 (CBX8) regulates cell differentiation, aging, and cell cycle progression in numerous carcinomas; however, the effects and underlying mechanisms of CBX8 in hepatocellular carcinoma (HCC) are rarely reported. We found that CBX8 expression in clinical HCC specimens correlates inversely with patient survival. In HCC cells, we found that enforced overexpression of CBX8 induces epithelial–mesenchymal transition, invasive migration, and stem cell-like traits, which are associated with increased tumor growth and metastasis in mice. Conversely, CBX8 silencing inhibits the aggressive phenotype of HCC cells that have high CBX8 expression. Mechanistically, CBX8 modulates H3K27me3 in the gene promoter of bone morphogenetic protein 4 (BMP4), which is associated with active BMP4 transcription and, consequently, the activation of Smads and mitogen-activated protein kinases. BMP4 expression reverses the effects of CBX8 silencing in inhibiting epithelial–mesenchymal transition, stemness, and metastasis. Our results establish CBX8 as a critical driver of HCC stem cell-like and metastatic behaviors and characterize its role in modulating BMP4 expression. These findings have implications for the targeting of CBX8 as an approach to HCC prognosis and treatment.

Heat Shock Proteins (HSP) are a category of proteins for stress regulation being highly conservative in respect of evolutionary sequence, which mainly consist of HSP10, HSP27, HSP40, HSP60, HSP70, HSP90, HSP110 and multiple sub-types thereof. The main function is to maintain the normal functional structure of proteins through the molecular chaperone role. Simultaneously, it can also play a role of cell protection and immunoregulation. The expression of HSP is extensively high in digestive tract cancer and closely related to multiple biological functions such as tumor cell proliferation, cell apoptosis, cell cycle, invasion and migration and drug resistance in chemical therapy, etc. Simultaneously, it has also verified that the inhibitor of HSP can resist the tumor promotion effect effectively in vitro and in vivo. However, the current researches are being concentrated on the inhibitors of HSP70 and HSP90. Further clinic research verification is also needed. In summary, HSP are not only potential tumor biomarkers in early diagnosis and prognosis monitoring to digestive tract cancer, but also a potential target for effective therapy to tumors.

PURPOSE:To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis.METHODS:90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology.RESULTS:Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group.CONCLUSION:Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.

Liver metastasis is one of the major causes of death in patients with colorectal cancer, and although treatment has improved recently, the long-term survival rate of patients has not improved significantly. In the present study, we used immunohistochemistry to determine that phosphoprotein enriched in astrocytes-15 kDa (PEA15) was highly expressed in colorectal cancer tissues and liver metastatic cancer tissues. It was also highly expressed in metastatic colorectal cancer patients compared to non-metastatic patients. Through clinicopathological data of patients with liver metastasis of colorectal cancer, we found that high expression of PEA15 was positively correlated with TNM staging, liver metastasis and poor prognosis of colorectal cancer patients. Using confocal immunofluorescence microscopy, western blotting and cell proliferation, migration and invasion assays, we also determined that PEA15 could promote cancer cell proliferation in vitro and in vivo, epithelial mesenchymal transition (EMT) and the characteristics of cancer stem cells in vitro, thus promoting the abilities of invasion and migration. In addition, we revealed that PEA15 promoted the liver metastasis of colorectal cancer cells in a xenograft tumor metastasis model. In addition, concerning the mechanism, we used gene chip analysis to determine that PEA15 upregulated the ERK/MAPK signaling pathway in colorectal cancer cells. Therefore, we concluded that PEA15 may be a potential biomarker for liver metastasis of colorectal cancer therapy. Collectively, PEA15 promoted the development of liver metastasis of colorectal cancer through the ERK/MAPK signaling pathway.

USP家族是去泛素化酶家族中种类最多、结构最复杂的一类,由三个区域组成,形成一个类似手型的结构.包含催化结构区域以及蛋白质结合区域,作用于底物蛋白的泛素分子或者多聚泛素链从而将其降解.其广泛参与到肿瘤发生、细胞分化、信号传导等过程中,近些年逐渐成为研究热门.作为USP家族中新发现的一个成员,USP3近年来在DNA损伤修复、抗感染免疫及肿瘤发生发展等领域中研究渐多,现将其相关研究进展进行简要综述,以供参考.

In this study, we investigated the role of microRNA-644a (miR-644a) in the growth and survival of hepatocellular carcinoma (HCC) cells. MiR-644a levels were lower in HCC tissues than in adjacent peri-cancerous tissues (n = 135). MiR-644a expression was inversely correlated with heat shock factor 1 (HSF1) expression, tumour diameter and TNM stage. Moreover, HepG2 and SMMC-7721 cell lines showed lower miR-644a expression than normal L-O2 hepatocytes. MiR-644a overexpression in HepG2 and SMMC-7721 cells increased apoptosis by downregulating HSF1. Dual luciferase reporter assays confirmed the presence of a miR-644a binding site in the 3’-untranslated region (3’-UTR) of HSF1. Xenograft tumours derived from SMMC-7721 cells transfected with a miR-664a mimic showed less growth than tumours derived from untransfected controls. Protein chip analysis revealed that miR-644a-overexpressing SMMC-7721 and HepG2 cells strongly expressed pro-apoptotic BH3-only proteins, such as BID, BAD, BIM, SMAC, Apaf-1 and cleaved caspases-3 and -9. These findings suggest miR-644a promotes apoptosis in HCC cells by inhibiting HSF1.

The aim of the present study was to investigate the association between tubulin folding cofactor B (TBCB) expression and ischemia-reperfusion injury (IRI) in mice. A total of 48 C57BL/6 mice were randomly divided into a control group (Sham, n=6) and an ischemia-reperfusion group (n=42). The ischemia-reperfusion group was further divided into 6 subgroups as per different times after reperfusion (2, 4, 6, 8, 12 and 24 h), with 7 mice per subgroup. A hepatic IRI model was established in mice by clamping the hepatic hilum. Morphology, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin 6 (IL-6) and tumor necrosis factor- (TNF-), and the expression level of TBCB were detected. Compared with the control group, the livers from the ischemia-reperfusion group were significantly changed, particularly at 12 h following ischemia-reperfusion, with obvious hepatic cell degeneration and necrosis. The ALT, AST, IL-6 and TNF- levels in the sera of the mice in the hepatic ischemia-reperfusion group were increased at all time points following ischemia-reperfusion, and were the highest at 12 h, demonstrating statistically significant differences when compared with the control group (P<0.05). Furthermore, the expression levels of TBCB, TNF- and IL-6 were significantly increased at all time-points following ischemia-reperfusion, and were the most significant at 12 h. At 24 h following ischemia-reperfusion, the expression levels had decreased. The present study indicated that TBCB expression is associated with TNF- and IL-6 expression levels in mice with hepatic ischemia-reperfusion, and may be key in the development of liver injury during ischemia-reperfusion in mice.