Expression of CASC8 RNA in Human Pancreatic Cancer Cell Lines.

A lot of long non-coding RNAs (lncRNAs) are expressed in human cells in a number of transcripts of different lengths and composition of exons. In case of cancer-associated lncRNAs, an actual task is to determine their specific isoforms, since each transcript can perform its own function in carcinogenesis and might have a unique expression profile in various types of tumors. For the first time, we analyzed the expression of CASC8 lncRNA in human pancreatic ductal adenocarcinoma cell lines and found an abundant isoform that was previously considered as the minor one in this type of cancer. We also revealed extremely high expression levels of all CASC8 transcripts in MIA PaCa-2 cells and, conversely, the lack of this lncRNA in PANC-1. This allows to use them as convenient models for further in vitro studies.

Deregulation of hepatocyte nuclear factor 4 (HNF4)as a marker of epithelial tumors progression.

Tissue-specific transcription factors forming the regulatory cascades which determine the specification and differentiation of epithelial cells during embryogenesis, play the central role in the control of functional and morphological properties of different cell types. Hepatocyte nuclear factors (HNFs) network is one of the most investigated tissue-specific regulatory systems which controls the specification and maintenance of differentiation of several epithelial cell types. Nuclear receptor HNF4α is one of the central elements of this regulatory network in the liver. We have found that deregulation of this gene is associated with rodent and human hepatocellular carcinoma (HCC) progression and induces the increase of proliferation rate, loss of epithelial morphology, dedifferentiation and metastasis. Restoration of HNF4α expression in dedifferentiated cells induced partial reversion of highly malignant phenotype both in vitro and in vivo. In human HCC samples HNF4α transcription was completely lost or significantly decreased in about 70% of HCCs, not associated with hepatitis B virus infection. Decrease of HNF4α isoforms expression correlated with poor prognosis. Thus we propose HNF4α is a candidate tumor suppressor for hepatic cells. Dysfunction of different HNFs was also reported in other epithelial tumors. We suppose that tissue-specific transcription factors which control the key steps of definite differentiation programs and are capable to receive and modulate extracellular signals can be considered as promising tumor suppressor candidates for their corresponding tissues.

[Suppression of alpha-fetoprotein gene expression in somatic hybrids of AFP-positive and AFP-negative clones of rat hepatoma]. / Podavlenie ékspressii gena al'fa-fetoproteina v somaticheskikh gibridakh AFP-polozhitel'nogo i AFP-otritsatel'nogo klonov krysinoi gepatomy.

The presented study is devoted to investigation of molecular mechanisms regulating alpha-fetoprotein (AFP) gene expression at transcriptional level. The study was carried out on AFP-positive and AFP-negative clones of rat hepatoma McA-RH 7777 that also differ in hepatocyte nuclear factors (HNF) 1 and 4 transcription levels. To examine a hypothesis of existence in AFP-non-producing clones a transcriptional factor that downregulates this gene expression, we have obtained somatic hybrids of AFP-positive and AFP-negative clones. In the obtained hybrids AFP gene expression is decreased while expression of HNF1, one of the main AFP promoter activators, is maintained. These data indicate an existence of a repressor in AFP-negative clones that determines AFP gene downregulation regardless of the HNF1 expression level.