Chaojie Liang

LncSHRG promotes hepatocellular carcinoma progression by activating HES6

Hepatocellular carcinoma, one of the most common cancers, leads to mass mortality worldwide currently. However, the underlying mechanism of its oncogenesis remains to be elucidated. Here we identified that a long noncoding RNA, lncSHRG, was greatly upregulated in human hepatocellular carcinoma samples. We found that lncSHRG was essential for liver cancer cell proliferation and tumor propagation in mice. In mechanism, lncSHRG recruits SATB1 to bind to HES6 promoter and initiates HES6 expression. HES6, which is highly expressed in hepatocellular carcinoma, promotes tumor cell proliferation. High expression level of HES6 is positively correlated with clinical severity and poor prognosis of people with hepatocellular carcinoma. Altogether, our research provides a new insight on the mechanism of hepatocellular carcinoma progression.

Downregulation of DcR3 sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis

Decoy receptor 3 (DcR3) has been recently described as an antiapoptosis and prometastasis factor since it can competitively bind to FasL, TL1A, and LIGHT, and it is highly expressed in many malignant tumors. Downregulation of DcR3 can promote tumor cell apoptosis and inhibit metastasis. A previous study demonstrated that reduction of DcR3 could induce tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in pancreatic cancer cells. However, whether such an effect is seen in hepatocellular carcinoma (HCC) remains to be explored. This study was designed to investigate the sensitivity of HCC cells to TRAIL after silencing DcR3, and this was done by evaluating the expression of DcR3 in HCC cells and the effect on TRAIL-mediated apoptosis after downregulation of DcR3. Our data showed that DcR3 was highly expressed in HepG2, BEL-7402, Hep3B, Huh-7, MHCC97H, and SMCC7721 cell lines compared with normal liver cell line LO-2. Both HepG2 and BEL-7402 were tolerant to TRAIL-mediated apoptosis, and the tolerance was negatively correlated to the expression of DcR3. Silencing of DcR3 with shRNA and treatment with TRAIL induced obvious apoptosis in HepG2 and BEL-7402, with more cancer cells found in the G1 phase. SiDcR3 combined with TRAIL could induce activation of caspases-3, -8, and -9, raise the expression of the apoptotic protein Bax, and reduce the expression of antiapoptotic proteins (Bcl-2, Mcl-1, Bcl-XL, IAP-2, and survivin). Caspase-8 inhibitor Ac-IETD-CHO significantly decreased the activation of caspase cascade, indicating that the extrinsic pathway may have a vital role in the apoptotic events induced by SiDcR3/TRAIL. Furthermore, our results showed that the TRAIL death receptor 5 (DR5) was upregulated and that DR5 neutralizing antibody abrogated the effect of SiDcR3. Our results demonstrated that downregulation of DcR3 could enhance TRAIL-mediated apoptosis in HCC through the death receptor pathway. In the future, this might be useful as a clinical treatment method of liver cancer.

Long non-coding RNA CRNDE as a potential prognostic biomarker in solid tumors: A meta-analysis

BACKGROUND AND AIM Long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) has been demonstrated to be highly expressed in many malignant tumors; however, the role of CRNDE in cancer remains undetermined because of limitations in sample size. We conducted a meta-analysis to assess the role of CRNDE in cancer. METHODS PubMed, Medline, Cochrane Library, Web of Science, EMBASE database, Ovid, Chinese CNKI, and Chinese WanFang database were systematically searched. The relation between CRNDE and the clinicopathological characteristics and prognosis of patients with cancer was determined using pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence interval (CI). RESULTS Thirteen studies with 1570 patients were included. The pooled results indicated that high CRNDE expression was related to lymph node metastasis (YES vs. NO: OR = 3.50, 95% CI = [1.05, 8.09]) and TNM stage (I + II vs. III + IV: OR = 0.26, 95% CI = [0.18, 0.37]) but not to gender, tumor size, and differentiation. High CRNDE expression indicated poor overall survival (OS) (HR = 2.06, 95% CI = [1.66, 2.47]). CRNDE could be an independent predictive factor for OS (HR = 1.62, 95% CI = [1.15, 2.08]) in patients with cancer. CONCLUSION Therefore, high CRNDE expression was associated with advanced clinicopathological characteristics, and CRNDE could be used as a reliable prognostic biomarker in human cancer. However, more high-quality studies with a large sample size are needed to support this meta-analysis.

Clinicopathological and prognostic significance of OCT4 in patients with hepatocellular carcinoma: a meta-analysis

Background and aims Octamer-binding transcription factor 4 (OCT4) has been implicated in the development of hepatocellular carcinoma (HCC), although the findings are controversial. We conducted a meta-analysis to assess the correlation between OCT4 and the clinicopathological characteristics and the prognostic value in HCC. Methods An electronic search for relevant articles was conducted in PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and Chinese WanFang database. Correlations between OCT4 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios and hazard ratios with 95% CIs were calculated using STATA 14.2 software. Results A total of 10 trials with 985 patients were included. Positive OCT4 expression was correlated with tumor size, tumor numbers, differentiation, and TNM stage. OCT4 expression was not correlated with gender, age, hepatitis B surface antigen, alfa-fetoprotein, liver cirrhosis, vascular invasion, or tumor encapsulation. OCT4 expression was associated with poor 3- and 5-year overall survival, and disease-free survival rate. Conclusion OCT4 expression was associated with tumor size, tumor numbers, differentiation, and TNM stage in HCC. OCT4 may be a useful prognostic biomarker for HCC.

The clinicopathological and prognostic value of Nanog in human gastrointestinal luminal cancer: A meta-analysis

BACKGROUND Recent studies have demonstrated that the over-expression of Nanog contributes to the progression of various malignant tumors. However, the clinicopathological and prognostic role of Nanog in gastrointestinal luminal cancer remains controversial. Therefore, we conducted a meta-analysis to assess the role of Nanog in gastrointestinal luminal cancer. METHODS An electronic search for relevant literature was performed in PubMed, Cochrane Library, Web of Science, and EMBASE databases. The relationships between Nanog expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by STATA14.2 and RevMan 5.3 software. RESULTS A total of 9 studies with 1526 patients were included in this meta-analysis. The positive expression of Nanog was related to gender, depth of infiltration, differentiation, and TNM stage; however, it was not associated with age, tumor size, or lymph node metastasis. Moreover, positive Nanog expression was correlated with a poor overall survival (OS) and poor disease-free survival (DFS) in gastrointestinal luminal cancer. CONCLUSION The pooled results suggested that Nanog expression was associated with gender, depth of infiltration, differentiation, and TNM stage, and Nanog may be a potential biomarker to predict the prognosis of gastrointestinal luminal cancer.

Prognostic and clinicopathological value of Nanog in hepatocellular carcinoma: A meta-analysis

BACKGROUND AND AIMS Recently, studies indicate that Nanog is over-expressed in hepatocellular carcinoma (HCC); however, the relationship between Nanog expression and clinicopathological and prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore the role of Nanog in HCC. METHODS Articles were included from PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and the Chinese WanFang database. The relationships between Nanog expression, clinicopathological features, and survival rate were calculated. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with STATA14.2. RESULTS A total of 845 patients from 9 articles were enrolled. Positive Nanog expression was correlated with HBsAg, differentiation, and TNM stage, although it was not related to gender, age, alpha-fetoprotein (AFP), tumor size, tumor number, liver cirrhosis, and vascular invasion. Positive Nanog expression indicates a poor 3-year and 5-year overall survival and disease-free survival rate. CONCLUSION The results show that Nanog expression was related to HBsAg, differentiation, and TNM stage in HCC. Nanog may be an unfavorable prognostic biomarker for HCC.

The clinicopathological and prognostic value of long non-coding RNA ZEB1-AS1 in solid tumors: A meta-analysis

BACKGROUND AND AIM Studies have reported that Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is overexpressed in many malignant tumors. However, the sample size in those studies was limited, so the clinicopathological and prognostic value of ZEB1-AS1 in solid tumors remains undetermined, Accordingly, the aim of this meta-analysis was to evaluate the relationship between the expression of lncRNA ZEB1-AS1 and clinicopathological characteristics and prognosis in patients with solid tumors. METHODS Pooled odds ratios (ORs) and hazard ratios (HRs) were estimated with 95% confidence interval (CI) to assess the relation between ZEB1-AS1 and the clinicopathological characteristics and prognosis of patients with cancer. RESULTS A total of 10 studies, comprising 861 patients, were included in this meta-analysis. The pooled results suggested that high ZEB1-AS1 expression was related to low differentiation (low vs. high + moderate: OR = 2.99, 95% CI = [2.03, 4.39]), increased lymph node metastasis (YES vs. NO: OR = 4.62, 95% CI = [2.90, 7.37]) and advanced TNM stage (I + II vs. III + IV: OR = 0.41, 95% CI = [0.23, 0.75]), but not to gender and tumor size. Moreover, high ZEB1-AS1 expression was associated with poor overall survival (OS; HR = 1.86, 95% CI = [1.57, 2.14]) and disease-free survival (DFS; HR = 2.03, 95% CI = [1.28, 2.77]). Thus, ZEB1-AS1 could be an independent predictive factor for OS (HR = 2.07, 95% CI = [1.57, 2.56]) in patients with cancers. CONCLUSION High expression of ZEB1-AS1 was associated with advanced clinicopathological characteristics, and ZEB1-AS1overexpression may be a potential prognostic biomarker in human cancer. However, more studies involving various tumor types and large sample size are needed.

miR-564 inhibits hepatocellular carcinoma cell proliferation and invasion by targeting the GRB2-ERK1/2-AKT axis

Recent studies have shown that miR-564 is closely related to the development of various tumors, including breast cancer, lung cancer and glioma. However, few studies have examined miR-564 in hepatocellular carcinoma (HCC). Here, we demonstrated that miR-564 expression in HCC tissues was lower than that in adjacent noncancerous tissues and that miR-564 expression was associated with tumor size, tumor number and vein invasion. Bioinformatics analyses showed that low levels of miR-564 were correlated with poor prognosis. Furthermore, upregulation of miR-564 impaired SMCC7721 and MHCC97H cell proliferation, migration and invasion in vitro and reduced tumorigenesis in vivo. Next, we found that GRB2 was a direct target gene of miR-564 in the HCC cell lines. GRB2 was highly expressed in HCC tissues and negatively correlated with miR-564 expression levels. When GRB2 was downregulated by GRB2-siRNA, HCC cell proliferation, invasion and metastasis were impaired, and restoring GRB2 expression partially reversed the inhibitory effects of miR-564. Western blot analysis showed that miR-564 overexpression reduced GRB2 expression in HCC cell lines and inhibited ERK1/2 and AKT phosphorylation. miR-564 overexpression also upregulated the epithelial-like cell marker E-cadherin and downregulated the interstitial cell-like markers N-cadherin and vimentin. These results suggest that miR-564 inhibits the malignant phenotype of HCC cells by targeting the GRB2-ERK1/2-AKT axis. Consequently, miR-564 may be used as a prognostic marker and therapeutic target for HCC.

Clinicopathological and prognostic significance of FoxM1 in hepatocellular carcinoma patients: a meta-analysis

Background and aims Recently, the abnormal expression of FoxM1 has been found in many malignant tumors. However, the clinicopathological and prognostic value of FoxM1 expression in hepatocellular carcinoma (HCC) patients remains controversial. We conducted a meta-analysis to establish the relationship between FoxM1 expression and the clinicopathological features and prognostic value in patients with HCC. Methods An electronic search for relevant articles was conducted according to a set of criteria in the PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI and Chinese WanFang databases. The correlation data between FoxM1 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were calculated using STATA14.2. Results A total of 14 studies comprising of 2,036 patients were enrolled in this meta-analysis. The results showed that FoxM1 expression was related to the incidence, tumor size (>5 cm), vascular invasion, differentiation and TNM stage. Moreover, overexpression of FoxM1 indicated a poor 3- and 5-year overall survival rate (OS) and recurrence-free survival rate (disease-free survival rate). Conclusion Our meta-analysis indicated that FoxM1 expression was associated with incidence, tumor size (>5 cm), vascular invasion, differentiation and TNM stage. Accordingly, FoxM1 may be a reliable prognostic biomarker for patients with HCC. However, additional high-quality studies are still needed to further support these findings.

Clinicopathological significance and prognostic role of p-STAT3 in patients with hepatocellular carcinoma

Background and aim Constitutive activation of STAT3 through its phosphorylation (p-STAT3) plays a key role in the development and progression of various cancers. However, the relationship between p-STAT3 expression and the clinicopathological features and prognostic value in patients with hepatocellular carcinoma (HCC) remains controversial. We conducted a meta-analysis to evaluate the role of p-STAT3 in HCC. Methods The PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI, and Chinese Wanfang databases were searched using the appropriate terms to find the relevant studies on p-STAT3 and HCC. The relationship between p-STAT3 expression and clinicopathological characteristics and prognostic value was established. Pool odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were calculated using the STATA 14.2 software. Results The eight articles included in this meta-analysis comprised 752 patients. Expression of p-STAT3 was associated with incidence, age, liver cirrhosis, tumor size, vascular invasion, and TNM stage of HCC, but it was not related to gender, alpha-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), number of tumors, and tumor differentiation. Additionally, the expression of p-STAT3 was related to a poor 3- and 5-year overall survival rate and disease-free survival rate. Conclusion Expression of p-STAT3 was associated with the incidence, age, liver cirrhosis, tumor size, vascular invasion, and TNM stage. Thus, p-STAT3 can be a reliable prognostic biomarker for HCC. Further high-quality studies with larger numbers of patients are needed.