Tianzhen Wang

Competing endogenous RNA networks in human cancer: hypothesis, validation, and perspectives.

Non-coding RNAs represent a majority of the human transcriptome. However, less is known about the functions and regulatory mechanisms of most non-coding species. Moreover, little is known about the potential non-coding functions of coding RNAs. The competing endogenous RNAs (ceRNAs) hypothesis is proposed recently. This hypothesis describes potential communication networks among all transcript RNA species mediated by miRNAs and miRNA-recognizing elements (MREs) within RNA transcripts. Here we review the evolution of the ceRNA hypothesis, summarize the validation experiments and discusses the significance and perspectives of this hypothesis in human cancer.

Functions and Mechanisms of Long Noncoding RNAs in Ovarian Cancer.

Abstract Long noncoding RNAs (lncRNAs) are longer than 200-nucleotide, noncoding transcripts in length, have a variety of biological functions, and are closely associated with tumor development. Ovarian cancer, as 1 of the 3 common gynecological malignancies, is the leading cause of death in women with gynecological malignant tumor. In this study, a review of the literature found that lncRNAs H19, LSINCT5, and XIST have a close relationship to the development of ovarian cancer occurrence, growth, invasion, and metastasis, and they can promote ovarian cancer cell proliferation. Hence, in this article, the progress of above-mentioned 3 kinds of lncRNAs in ovarian cancer was reviewed and designed to help in the diagnosis, treatment, and prognosis of ovarian cancer.

Noncoding RNAs in the development, diagnosis, and prognosis of colorectal cancer

More than 90% of the human genome is actively transcribed, but less than 2% of the total genome encodes protein-coding RNA, and thus, noncoding RNA (ncRNA) is a major component of the human transcriptome. Recently, ncRNA was demonstrated to play important roles in multiple biological processes by directly or indirectly interfering with gene expression, and the dysregulation of ncRNA is associated with a variety of diseases, including cancer. In this review, we summarize the function and mechanism of miRNA, long intergenic ncRNA, and some other types of ncRNAs, such as small nucleolar RNA, circular ncRNA, pseudogene RNA, and even protein-coding mRNA, in the progression of colorectal cancer (CRC). We also presented their clinical application in the diagnosis and prognosis of CRC. The summary of the current state of ncRNA in CRC will contribute to our understanding of the complex processes of CRC initiation and development and will help in the discovery of novel biomarkers and therapeutic targets for CRC diagnosis and treatment.

Hepatitis B virus induces G1 phase arrest by regulating cell cycle genes in HepG2.2.15 cells

BackgroundTo investigate the effect of HBV on the proliferative ability of host cells and explore the potential mechanism.MethodsMTT, colony formation assay and tumourigenicity in nude mice were performed to investigate the effect of HBV on the proliferative capability of host cells. In order to explore the potential mechanism, cell cycle and apoptosis were analysed. The cell cycle genes controlling the G1/S phase transition were detected by immunohistochemistry, westernblot and RT-PCR.ResultsHepG2.2.15 cells showed decreased proliferation ability compared to HepG2 cells. G1 phase arrest was the main cause but was not associated with apoptosis. p53, p21 and total retinoblastoma (Rb) were determined to be up-regulated, whereas cyclinE was down-regulated at both the protein and mRNA levels in HepG2.2.15 cells. The phosphorylated Rb in HepG2.2.15 cells was decreased.ConclusionsOur results suggested that HBV inhibited the capability of proliferation of HepG2.2.15 cells by regulating cell cycle genes expression and inducing G1 arrest.

Hepatoma cell line HepG2.2.15 demonstrates distinct biological features compared with parental HepG2

AIM To investigate the biological features of hepatitis B virus (HBV)-transfected HepG2.2.15 cells. METHODS The cell ultrastructure, cell cycle and apoptosis, and the abilities of proliferation and invasion of HBV-transfected HepG2.2.15 and the parent HepG2 cells were examined by electron microscopy, flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trans-well assay. Oncogenicity of the two cell lines was compared via subcutaneous injection and orthotopic injection or implantation in nude mice, and the pathological analysis of tumor formation was performed. Two cytoskeletal proteins were detected by Western blotting. RESULTS Compared with HepG2 cells, HepG2.2.15 cells showed organelle degeneration and filopodia disappearance under electron microscope. HepG2.2.15 cells proliferated and migrated slowly in vitro, and hardly formed tumor and lung metastasis in nude mice. Flow cytometry showed that the majority of HepG2.2.15 cells were arrested in G1 phase, and apoptosis was minor in both cell lines. Furthermore, the levels of cytoskeletal proteins F-actin and Ezrin were decreased in HepG2.2.15 cells. CONCLUSION HepG2.2.15 cells demonstrated a lower proliferation and invasion ability than the HepG2 cells due to HBV transfection.

The response to interferon is influenced by hepatitis B virus genotype in vitro and in vivo.

PURPOSE To investigate the effectiveness of an interferon administration on different genotypes of hepatitis B virus (HBV) in vitro and in vivo. METHODS In vitro, we transfected plasmids carrying different HBV genotypes including recently identified new genotype I into HepG2 and HuH7 cells, then treated with standard interferon alpha (IFN-α); in vivo, we treated mice with pegylated interferon alpha (Peg-IFN-α) after injection with HBV DNA of different genotypes. The culture supernatants from cell culture and sera from mice were collected and used in hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays by ELISA and HBV DNA measurement by PCR. RESULTS Both in cell culture and in mouse model, it was observed that HBV genotypes A and B exhibited significantly better response to IFN-α2a or Peg-IFN-α2a in terms of reduced expression of HBsAg, HBeAg and the HBV DNA level as compared to HBV genotypes C and D. Moreover, the inhibitory effect of IFN-α2a or Peg-IFN-α2a on HBV genotype I was greater than on genotype C or D, but less than genotype A. However, there was no significant response difference between genotypes A and B, C and D, B and I, respectively. CONCLUSION The effectiveness of IFN/Peg-IFN to suppress HBV replication is dependent on different HBV genotypes. IFN/Peg-IFN is more effective on HBV genotype A or B than on genotype C, D or I. Treatment regimens are suggested to be adapted to HBV genotype.

Detection of viral antigens in renal tissue of glomerulonephritis patients without serological evidence of hepatitis B virus and hepatitis C virus infection.

OBJECTIVES Glomerulonephritis is an important extrahepatic manifestation of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. HBV and HCV infection may be occult, and they are often overlooked by both patients and doctors. The aim of this study was to assess the importance of HBV and HCV infection in glomerulonephritis patients with undetectable HBV surface antigen (HBsAg) and HCV antibody in serum. METHODS The HBsAg, the HBV core antigen (HBcAg), and the HCV antigen were detected using immunohistochemistry in frozen renal tissues of 500 glomerulonephritis patients without serological evidence of HBV and HCV infection. Electron microscopy was used to trace the virus particles, and clinicopathological features were also reviewed. RESULTS HBsAg or HBcAg was positive in nine out of 500 cases (9/500, 1.8%). Three cases were HBsAg-positive and another six cases were HBcAg-positive. The HCV antigen was found in eight cases (8/500, 1.6%). There was one case of HBV and HCV co-infection (1/500, 0.2%). Under electron microscopy, virus particles were found in the base membrane and cytoplasm of endotheliocytes in the glomerulus. The most common clinical manifestation was nephrotic syndrome (9/18), followed by nephritic syndrome (7/18). Membranous nephropathy was the most common pathological diagnosis (5/18), followed by mesangioproliferative glomerulonephritis (4/18) and IgA nephropathy (4/18). CONCLUSIONS Occult HBV and HCV infection might be implicated in HBV- or HCV-associated glomerulonephritis. More attention should be focused on the underlying cause.

From cell membrane to the nucleus: an emerging role of E-cadherin in gene transcriptional regulation

E‐cadherin is a well‐known mediator of cell–cell adherens junctions. However, many other functions of E‐cadherin have been reported. Collectively, the available data suggest that E‐cadherin may also act as a gene transcriptional regulator. Here, evidence supporting this claim is reviewed, and possible mechanisms of action are discussed. E‐cadherin has been shown to modulate the activity of several notable cell signalling pathways, and given that most of these pathways in turn regulate gene expression, we proposed that E‐cadherin may regulate gene transcription by affecting these pathways. Additionally, E‐cadherin has been shown to accumulate in the nucleus where documentation of an E‐cadherin fragment bound to DNA suggests that E‐cadherin may directly regulate gene transcription. In summary, from the cell membrane to the nucleus, a role for E‐cadherin in gene transcription may be emerging. Studies specifically focused on this potential role would allow for a more thorough understanding of this transmembrane glycoprotein in mediating intra‐ and intercellular activities.

Detection of hepatitis B virus DNA in paraffin-embedded intrahepatic and extrahepatic cholangiocarcinoma tissue in the northern Chinese population

This study explored the importance of hepatitis B virus infection in cholangiocarcinoma pathogenesis in northern China. The clinical data of 66 patients with cholangiocarcinoma were analyzed. The hepatitis B virus gene was amplified using nested polymerase chain reaction, and the hepatitis B virus-related antigen was detected using immunohistochemistry in formalin-fixed, paraffin-embedded tissue from patients with intrahepatic cholangiocarcinoma (n = 23) and extrahepatic cholangiocarcinoma (n = 43). Hepatitis B surface antigen seropositivity was found in 52.2% (12/23) of intrahepatic cholangiocarcinoma cases and 13.9% (6/43) of extrahepatic cholangiocarcinoma cases. Hepatitis B virus DNA (X region) was detectable in 34.8% (8/23) of intrahepatic cholangiocarcinoma cases. Hepatitis B surface antigen and/or hepatitis B core antigen was detectable in 30.4% (7/23) of intrahepatic cholangiocarcinoma cases. All cases with detected viral protein were also positive for hepatitis B virus DNA. In contrast, no hepatitis B virus antigens or hepatitis B virus gene was detected in any of the 43 extrahepatic cholangiocarcinoma cases. Our findings strongly suggest that chronic hepatitis B virus infection is a significant risk factor for intrahepatic cholangiocarcinoma, but not for extrahepatic cholangiocarcinoma, in northern China. Hepatitis B virus infection is potentially independently associated with intrahepatic cholangiocarcinoma.

Comparison of the expression and function of Lin28A and Lin28B in colon cancer

Lin28A and Lin28B are highly conserved RNA binding proteins with similar structure and functions. Recent studies demonstrated that both of them act as oncogenes and promote cancer progression. However, few researches compared the expression and functions of both oncogenes in human malignant tumors at same time. Additionally, although the expression and role of Lin28B in colon cancer is frequently reported, the expression and functions of Lin28A in colon cancer are largely unknown. In this study, we have systematically evaluated the expressional pattern, mutation status and correlation of both Lin28A and Lin28B in colon cancer tissues for the first time, and compared the roles of Lin28A and Lin28B in the proliferation, migration, invasion and apoptosis of colon cancer cells in vitro. We have showed that they are co-expressed and have functional similarities, however, the molecular mechanisms underlying their similar functions may not be identical. This study contributes to clarify the similarities and differences of Lin28A and Lin28B in colon cancer progression.