Li-Shuai Qu

Long non-coding RNA SNHG20 predicts a poor prognosis for HCC and promotes cell invasion by regulating the epithelial-to-mesenchymal transition

BACKGROUND Recently, Accumulating evidence indicates that long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in human tumor biology and development. However, the expression pattern and biological function of lncRNA small nucleolar RNA host gene 20 (SNHG20) in hepatocellular carcinoma (HCC) remains largely unknown. METHODS The expression of SNHG20 in 96 paired HCC tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR) analysis. Kaplan-Meier survival analysis and log-rank test was used to reveal the association between SNHG20 expression and the overall survival time in HCC patients. CCK8 cell proliferation and transwell invasion assays were performed to analyze the cell proliferation and cell invasion ability. QRT-PCR and western-blotting analysis were performed to demonstrate the mRNA levels and protein expression of ZEB1, ZEB2 and relative epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and Vimentin). RESULTS We showed that the expression level of SNHG20 was significantly up-regulated in 96 pairs of HCC tissues and adjacent normal tissues. Higher SNHG20 expression was positively correlated with larger tumor size and advanced TNM stage, and negatively correlated with the over survival (OS) time for HCC patients. In vitro, loss-function assays revealed that knockdown of SNHG20 inhibited cell proliferation and invasion, whereas, gain-of-function promoted cell proliferation and invasion. Furthermore, knockdown of SNHG20 inhibited ZEB1, ZEB2, N-cadherin and Vimentin expression and up-regulated the E-cadherin expression in HCC cells. Mechanistic investigation revealed that SNHG20 could bind to enhancer of zeste homolog 2 (EZH2) and regulated E-cadherin expression. CONCLUSION Our results showed that the SNHG20/EZH2/E-cadhein regulator pathway might contribute to the development of novel therapeutic strategies for HCC patients.

Significance of viral status on recurrence of hepatitis B-related hepatocellular carcinoma after curative therapy: A meta-analysis.

The impact of viral status on recurrence of hepatitis B‐related hepatocellular carcinoma (HCC) after curative therapy remains controversial. This meta‐analysis aimed to determine whether the presence of viral load, genotype, specific mutation and antiviral therapy influenced HCC recurrence after curative therapy.

Effect of serum hepatitis B surface antigen levels on predicting the clinical outcomes of chronic hepatitis B infection: A meta-analysis

The impact of serum hepatitis B surface antigen (HBsAg) levels on the prognosis of chronic hepatitis B virus (HBV) infection remains unclear. This meta‐analysis aimed to determine whether serum HBsAg levels influenced the risk of cirrhosis and hepatocellular carcinoma (HCC) development. Furthermore, we explored the role played by serum HBsAg levels in prediction of spontaneous HBsAg seroclearance.

Effects of interferon therapy on development of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis : A meta-analysis of randomized controlled trials

Aim:  The role of interferon (IFN) therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)‐related cirrhosis remains controversial. This meta‐analysis aimed to determine whether IFN therapy reduced the incidence of HCC in HCV‐related cirrhotic patients.

Effect of combined mutations in the enhancer II and basal core promoter of hepatitis B virus on development of hepatocellular carcinoma in Qidong, China

To investigate the roles of mutations in enhancer II (Enh II), basal core promoter (BCP) and precore (PC) regions of hepatitis B virus (HBV) in the progression of hepatocellular carcinoma (HCC) in Qidong, China.

Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells

The 5-lipoxygenase (5-LOX) pathway has been associated with a variety of inflammatory diseases including asthma, atherosclerosis, rheumatoid arthritis, cancer and liver fibrosis. Several classes of 5-LOX inhibitors have been identified, but only one drug, zileuton, a redox inhibitor of 5-LOX, has been approved for clinical use. In the present study, 5-LOX was found to be overexpressed not only in pancreatic cancer cell lines but also in tissue samples of patients suffering from pancreatic adenocarcinoma. There was a close correlation between the tumor expression levels of 5-LOX mRNA and protein and the clinicopathological patient characteristics including lymph node metastasis and TNM stage. Zileuton suppressed the proliferation of SW1990 cells in a concentration- and time‑dependent manner. In addition, zileuton induced SW1990 cells to undergo apoptosis and significantly decreased 5-LOX expression. The number of apoptotic cells, estimated by flow cytometry, Annexin V/PI assay, TUNEL staining and sub‑diploid population was significantly higher than that of the control. These results suggest that the level of 5-LOX expression was increased in pancreatic cancer tissues and may be related to lymph node metastasis and TNM stage.

Therapeutic effects of triptolide via the inhibition of IL-1β expression in a mouse model of ulcerative colitis

The present study aimed to investigate the effect of triptolide (TL) on ulcerative colitis (UC) and explore the potential association between the therapeutic effects of TL and IL-1β expression using a 4,4-dimethyl-4-silapentane-1-sulfonic acid (DSS)-induced mouse model to simulate human UC. A total of 70 BALB/c female mice were randomly allocated into seven equal groups: Group A, blank control; group B, normal saline injection; group C, propylene glycol injection; group D (TL1), 0.2 mg/kg TL; group E (TL2), 0.4 mg/kg TL; group F (TL3), 0.6 mg/kg TL; and group G, dexamethasone injection. Mice activity, diet and stool characteristics were recorded daily. Mice were sacrificed by cervical dislocation on day 8, and disease activity indices, colon tissue histological scores and colonic histopathological scores were subsequently calculated. Serum levels of IL-1β were evaluated by enzyme-linked immunosorbent assay, and IL-1β expression levels were examined by reverse transcription-quantitative polymerase chain reaction with colonic mucosa specimen at the gene level and western blot analysis at the protein level. The IL-1β mRNA and protein expression levels were significantly elevated in the normal saline injection and propylene glycol injection groups compared with the blank control group and (P<0.01). In TL (TL2 and TL3)- and dexamethasone-treated mice, IL-1β expression levels were significantly decreased, as compared with the normal saline and propylene glycol injection groups (P<0.05). No significant difference was detected between TL (TL2 and TL3) and dexamethasone treatments. The results of the present study indicated that IL-1β expression was upregulated in the UC mouse model, which may be associated with the development and progression of UC. Furthermore, TL inhibited IL-1β expression, suggesting that TL may be a novel therapeutic target for the treatment of UC.

Effects of hepatitis B e-antigen on recurrence of hepatitis B-related hepatocellular carcinoma after curative resection: A meta-analysis

Aim:  The impact of hepatitis B e‐antigen (HBeAg) on recurrence of hepatocellular carcinoma (HCC) after curative resection remains controversial. This meta‐analysis aimed to determine whether the presence of HBeAg influenced the recurrence of HCC after curative resection.

Significance of viral status on prognosis of hepatitis B-related hepatocellular carcinoma after curative resection in East Asia

Tumor recurrence remains one major obstacle for further improving the prognosis of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) patients after curative liver resection. It has been widely reported that tumor size, positive surgical margin, macroscopic vascular invasion, tumor–node–metastasis stage and Edmondsons grade were significantly related to HCC recurrence. However, the association between HCC recurrence and important viral factors, including the HBV DNA levels, status of hepatitis B surface antigen and hepatitis B e‐antigen, levels of cccDNA and hepatitis B core‐related antigen, viral genotypes and specific viral sequence mutations remained controversial. Meanwhile, studies on the effect of postoperative adjuvant antiviral therapy on HCC recurrence have been relatively limited and have yielded conflicting results. Identification of certain viral risk factors for HCC recurrence and stratification of patient risk are very important to perform future surveillance programs. As a HBV hyperendemic region, the majority of HBV‐related HCC patients develop in East Asia. In this article, we thus systematically reviewed the risk of important viral factors involved in recurrent carcinogenesis and the role of adjuvant antiviral therapy in preventing tumor recurrence in this area.

Overexpression of DLX2 is associated with poor prognosis and sorafenib resistance in hepatocellular carcinoma

The mechanism underlying poor prognosis and sorafenib resistance in patients with hepatocellular carcinoma (HCC) is unknown and, to date, no useful predictive biomarkers of sorafenib resistance have been identified. Distal-less homeobox 2 (DLX2) is a transcription factor involved in cell cycle regulation that is closely correlated with cancer prognosis. In this study, we showed that DLX2 is overexpressed in HCC tissues and cell lines and that the level of DLX2 overexpression is positively correlated with histological grade, metastasis and Ki67 expression, which are indicators of poor prognosis. We also found that DLX2 accumulates in proliferating HCC cells, where it is associated with the expression of proliferating cell nuclear antigen (PCNA), Cyclin D1 and Cyclin A. Flow cytometry and cell counting kit-8 (CCK-8) assays indicated that DLX2 depletion causes cell cycle arrest at the G1 phase and hinders cell proliferation. Moreover, the sensitivity of HCC cells to sorafenib is restored when the DLX2 gene is knocked down using a short interfering RNA. We demonstrated that DLX2 facilitates sorafenib resistance by promoting the expression of markers of epithelial-mesenchymal transition and by activating the extracellular signal-regulated protein kinase pathway. Our findings reveal that DLX2 plays a regulatory role in HCC cell proliferation and suggests that targeting DLX2 represents a novel strategy to increase sorafenib efficacy in the management of HCC. In conclusion, DLX2 is a novel marker of poor prognosis and sorafenib resistance in patients with HCC.