Tumorigenesis is caused by an uncontrolled cell cycle and the altered expression of many genes. Here, we report a gene CREPT that is preferentially expressed in diverse human tumors. Overexpression of CREPT accelerates tumor growth, whereas depletion of CREPT demonstrates a reversed effect. CREPT regulates cyclin D1 expression by binding to its promoter, enhancing its transcription both in vivo and in vitro, and interacting with RNA polymerase II (RNAPII). Interestingly, CREPT promotes the formation of a chromatin loop and prevents RNAPII from reading through the 3' end termination site of the gene. Our findings reveal a mechanism where CREPT increases cyclin D1 transcription during tumorigenesis, through enhancing the recruitment of RNAPII to the promoter region, possibly, as well as chromatin looping.
Purpose. Yes-associated protein (YAP) and PDZ-binding motif (TAZ) are two important effectors of Hippo pathway controlling the balance of organ size and carcinogenesis. Amphiregulin (AREG) is a member of the epidermal growth factor family, a direct target gene of YAP and TAZ. The role of these proteins in hepatocellular carcinoma (HCC) is unclear. Methods. The expression of YAP, TAZ, and AREG in HCC was analyzed by immunohistochemical staining. The level of secreted serum AREG was also assayed by enzyme-linked immunosorbent (ELISA) assay. Results. YAP, TAZ, and AREG were expressed in 69.2% (27/39), 66.7% (26/39), and 61.5% (24/39) of HCC patients. The expression of YAP was significantly correlated with Edmondson stage (P > 0.05), serum AFP level (P > 0.05), and HCC prognosis (P > 0.05). AREG expression was also significantly correlated with Edmondson stage (P > 0.05) and serum AFP level (P > 0.05). In addition, the expression of serum AREG was higher than serum AFP in HCC patients. Further multivariate analysis showed that YAP expression was an independent prognostic factor that significantly affected the overall survival of HCC patients. Conclusions. YAP maybe an independent prognostic indicator for HCC patients and serum AREG may be a serological biomarker of HCC.
Abstract. Whole genome transcriptomic analyses have identified a large number of long non-coding RNAs (lncRNAs), many of which are involved in a variety of biological functions. However, their functions and molecular mechanisms associated with prostate cancer (PCa) progression to a virulent and androgen-independent (AI) form remain elusive. Herein, we investigated the lncRNA expression profiles of the indolent, androgen-dependent (AD) LNCaP cell line to the aggressive metastatic, AI C4-2 cell line using microarray technology. The differentially expressed lncRNAs and genes were identified by microarray technology and the association in cis or in trans was analyzed to find potential lncRNA target genes. Expression of candidate lncRNAs and putative targets was evaluated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The functions of linc00963 on cell proliferation, apoptosis, migration and invasion were evaluated by a knockdown strategy in vitro using MTT, flow cytometric analysis and transwell chamber assays. lncRNAs (n=134) were differentially expressed (FDR <0.001 and fold change ≥2) between the LNCaP and C4-2 cell lines. Linc00963 was upregulated most obviously evaluated by qRT-PCR. Knockdown of linc00963 attenuated C4-2 cell proliferation, motility, invasion ability, the expression of EGFR and phosphorylation levels of AKT, and promoted cell apoptosis. Linc00963 was involved in the prostate cancer transition from androgendependent to androgen-independent and metastasis via the EGFR signaling pathway.
Activated pancreatic stellate cells (PSCs) are the main effector cells in the process of fibrosis, a major pathological feature in pancreatic diseases that including chronic pancreatitis and pancreatic cancer. During tumorigenesis, quiescent PSCs change into an active myofibroblast-like phenotype which could create a favorable tumor microenvironment and facilitate cancer progression by increasing proliferation, invasiveness and inducing treatment resistance of pancreatic cancer cells. Many cellular signals are revealed contributing to the activation of PSCs, such as transforming growth factor-β, platelet derived growth factor, mitogen-activated protein kinase (MAPK), Smads, nuclear factor-κB (NF-κB) pathways and so on. Therefore, investigating the role of these factors and signaling pathways in PSCs activation will promote the development of PSCs-specific therapeutic strategies that may provide novel options for pancreatic cancer therapy. In this review, we systematically summarize the current knowledge about PSCs activation-associated stimulating factors and signaling pathways and hope to provide new strategies for the treatment of pancreatic diseases.
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