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Background: Defects of the growth arrest DNA damage-inducible gene 45β (Gadd45β) play an important role in the progression of tumor and confer resistance to chemotherapy. However, the role of Gadd45β in the apoptosis of hepatocellular carcinoma is still not clear. Purpose of this study was to explore the effect of Gadd45β on the apoptosis of liver cancer cells, and the possible mechanism was examined., Result: In this study, we first confirmed the decreased expression of Gadd45β in human liver cancer tissues and human liver cancer cell lines, when compared to the peri-tumor liver tissue and normal liver cells. And, it was found that Gadd45β could inhibit the stemness of liver cancer cells, enhancing the apoptosis of cancer cells induced by chemotherapy. Furthermore, the results showed that HCC tissues and cell lines showed a higher methylation status in Gadd45β promoter than that in peri-tumor tissues and normal liver cells. Methylation was then reversed by pretreatment of SMMC-7721 and Hep-3B with 5-azacytidine which is the DNA methyltransferase inhibitor. And the 5-azacytidine decreased the stemness of SMMC-7721 and Hep-3B, enhanced the sensitivity of SMMC-7721 and Hep-3B to cisplatin., Conclusions: Methylation mediated Gadd45β expression inhibited the stemness of liver cancer cells, promoting the chemotherapy-induced apoptosis. Thus Gadd45β may be the potential target for enhancing the chemosensitivity of human hepatocellular carcinoma.

Hepatocyte nuclear factor-1beta (HNF1β) was initially identified as a liver-specific transcription factor. It is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF1α. HNF1β plays an important role in organogenesis during embryonic stage, especially of the liver, kidney, and pancreas. Mutations in the HNF1β gene cause maturity-onset diabetes of the young type 5 (MODY5), renal cysts, genital malformations, and pancreas atrophy. Recently, it has been shown that the expression of HNF1β is associated with cancer risk in several tumors, including hepatocellular carcinoma, pancreatic carcinoma, renal cancer, ovarian cancer, endometrial cancer, and prostate cancer. HNF1β also regulates the expression of genes associated with stem/progenitor cells, which indicates that HNF1β may play an important role in stem cell regulation. In this review, we discuss some of the current developments about HNF1β and tumor, the relationship between HNF1β and stem/progenitor cells, and the potential pathogenesis of HNF1β in various tumors.

Development of a tumor is a very complex process, and invasion and metastasis of malignant tumors are hallmarks and are difficult problems to overcome. The tumor microenvironment plays an important role in controlling tumor fate and autophagy induced by the tumor microenvironment is attracting more and more attention. Autophagy can be induced by several stressors in the tumor microenvironment and autophagy modifies the tumor microenvironment, too. Autophagy has dual roles in tumor growth. In this review, we discussed the interaction between autophagy and the tumor microenvironment and the paradoxical roles of autophagy on tumor growth at different stages of tumor development.

Background: Ductular reactions (DRs) are well documented in many acute and chronic liver disease.The DRs are thought to be the transit amplifying cells deriving from activation of the stem/progenitor cell compartments of the liver. The aim of this study was to examine the presence of proliferative index of DR (PI-DR) and HPC markers' expression in HCCs after curative hepatectomy, as well as their relationship with clinicopathological features and prognosis., Results: Tissue microarray with peritumoral and intratumoral tissue samples of 120 HCCs after hepatectomy was analysed for peritumoral expression of proliferating cell nuclear antigen for PI-DR. Peritumoral and intratumoral expression status of HPC markers including EpCAM, OV6, CD133 and c-kit were also examined by immunohistochemistry. TMA analysis of HCCs revealed that peritumoral PI-DR strongly correlated with the degree of inflammation and fibrosis. The peritumoral PI-DR positively correlated with peritumoral HPC markers EpCAM, OV6, CD133 and c-kit expression. Moreover, there were highly significant correlations between peritumoral PI-DR and intratumoral HPC markers EpCAM, OV6, CD133 and c-kit expression. Further, multivariate analysis showed that peritumoral PI-DR was the independent prognostic factor for overall survival (HR; 3.316, P < 0.001), and peritumoral PI-DR had a better power to predict disease-free survival (HR; 2.618, P < 0.001)., Conclusions: Peritumoral PI-DR, as a valid surrogate for peritumoral and intratumoral expression of HPC markers, could be served as a potential prognostic marker for recurrence and survival in HCC after hepatectomy.