Pluripotency and self-renewal capacity of human embryonic stem cells (hESCs) are retained by hESCs related genes as OCT4, SOX2 and NANOG. These genes are shown high expression level in diverse cancer cells and have potential role in the carcinogenesis. On the contrary to this, several genes which are up-regulated in the differentiated hESCs are involved to suppress the carcinogenesis or proliferation of cells. We discovered several genes in immortalized lung fibroblast (WI-38 VA13) by suppression subtractive hybridization. Among them, we focused chromosome 6 open reading frame 62 (C6orf62) which is uncharacterized, mapped to 6p22.3 and generated to Hepatitis B virus X-transactivated proteins (HBVx-transactivated proteins, XTP). Aim of this study was to characterize C6orf62 through analyzing of expression pattern in various cell lines. Expression of C6orf62 was significantly up- regulated in diverse normal cell lines than cancer cell lines. And C6orf62 was up-regulated in differentiated hESCs (endothelial cells, neural cells) compared to those of undifferentiated hESCs. Also, C6orf62 in WI-38 cells was highly up-regulated during G1/S transition of the cell cycle. Taken together, C6orf62 is shown expression pattern similar to differentiated hESCs-associated genes which down-regulated in cancer cells. Therefore, we assume that C6orf62 may participate to suppress the proliferation and to induce differentiation through regulating the cell cycle.
Human embryonic stem (ES) cells retain the capacity for self‐renewal, are pluripotent and differentiate into the three embryonic germ layer cells. The regulatory transcription factors Oct4, Nanog and Sox2 play an important role in maintaining the pluripotency of human ES cells. The aim of this research was to identify unknown genes upregulated in human ES cells along with Oct4, Nanog, and Sox2. This study characterizes an unknown gene, named chromosome 1 open reading frame 31 (C1orf31) mapping to chromosome 1q42.2. The product of C1orf31 is the hypothetical protein LOC388753 having a cytochrome c oxidase subunit VIb (COX6b) motif. In order to compare expression levels of C1orf‐ 31 in human ES cells, human embryoid body cells, vascular angiogenic progenitor cells (VAPCs), cord‐blood endothelial progenitor cells (CB‐EPCs) and somatic cell lines, we performed RT‐PCR analysis. Interestingly, C1orf31 was highly expressed in human ES cells, cancer cell lines and SV40‐immortalized cells. It has a similar expression pattern to the Oct4 gene in human ES cells and cancer cells. Also, the expression level of C1orf31 was shown to be upregulated in the S phase and early G2 phase of synchronized HeLa cells, leading us to purpose that it may be involved in the S/G2 transition process. For these reasons, we assume that C1orf31 may play a role in on differentiation of human ES cells and carcinogenesis.
The HMG box containing protein (HBP) has a high mobility group domain and involved in the regulation of proliferation and differentiation of tissues. We screened HBP2 in glioblastoma using Suppression Subtractive Hybridization (SSH) and isolated human spermatogonial stem cell‐like cells (hSSC‐like cells) derived from patients of nonobstructive azoospermia (NOA). Expression of HBP2 was analyzed by RT‐PCR in undifferentiated stem cells (human Embryonic Stem Cells, hSSC‐like cells 2P) and spontaneous differentiated stem cells (hSSC‐like cells 4P). It was overexpressed in hESC and hSSC‐like cells 2P but not in hSSC‐like cells 4P. Also, the expression level of HBP2 was downregulated in colon tumor tissues compared to normal tissues. Specifically in synchronized WI‐38 cells, HBP2 was highly upregulated until the G1 phase of the cell cycle and gradually decreased during the S phase. Our results suggest that HBP2 was downregulated during the spontaneous differentiation of hSSC‐like cells. HBP2 was differently expressed in colon tissues and was related to G1‐progression in WI‐38 cells. It may play a role in the maintenance of an undifferentiated hSSC‐like cell state and transits from G1 to S in WI‐38 cells. This research was important that it identified a biomarker for an undifferentiated state of hSSC‐like cells and characterized its involvement to arrest during cell cycle in colon cancer.
The endogenous retrovirus-like elements (HERVs) found on several human chromosomes are somehow involved in gene regulation, especially during the transcription level. HERV-H, located on chromosome Xp22, may regulate gastrin-releasing peptide receptor (GRPR) in connection with diverse diseases. By suppression subtractive hybridization screen on SV40-immortalized lung fibroblast (WI-38 VA-13), we discovered that expression of HERV-HX2, a clustered HERV-H sequence on chromosome X, was upregulated in immortalized lung cells, compared to that of normal cells. Expression of HERV-HX2 was then analyzed in various cell lines, including normal somatic cells, cancer cells, SV40-immortalized cells, and undifferentiated and differentiated human embryonic stem cells. Expression of HERV-HX2 was specifically upregulated in continuously-dividing cells, such as cancer cells and SV40-immortalized cells. Especially, HERV-HX2 in HeLa cells was highly upregulated during the S phase of the cell cycle. Similar results were obtained in hES cells, in which undifferentiated cells expressed more HERV-HX2 mRNA than differentiated hES cells, including neural precursor and endothelial progenitor cells. Taken together, our results suggest that HERV-HX2 is upregulated in cancer cells and undifferentiated hES cells, whereas downregulated as differentiation progress. Therefore, we assume that HERV-HX2 may playa role on proliferation of cancer cells as well as differentiation of hES cells in the transcriptional level.
Background : The young stem of Cinnamomum cassia (YSC) as traditional Chinese medicines has been reported to show a variety of pharmacological properties such as anti-allergy, insecticidal, antimicrobial, antiulcer, anti-inflammatory, immune-suppressive, and neuronal death prevention, tyrosinase inhibition and anticancer, antioxidant and free radical scavenging, as well as antidiabetic and aldose reductase inhibition activities. In this study, we elucidated apoptotic effect and potential molecular mechanism of hot water extracts from YSC (YSC-HW) against human colorectal cancer cells. Methods and Results : YSC-HW treatment increased ROS level and induced ROS-dependent DNA damage in human colorectal cancer cells. ROS generation mediated by YSC-HW induced DNA induced apoptosis and reduction of cell viability in human colorectal cancer cells. YSC-HW ROS-dependently induced NF-kB activation through p65 nuclear translocation via IkB-α degradation, which exerted the induction of apoptosis. In addition, YSC-HW activated ATF3 expression dependent on ROS, which resulted in apoptosis. Conclusion : Our results suggest that YSC-HW may induce apoptosis through ROS-activation of NF-kB and ATF3 in human colorectal cancer cells. From these findings, YSC-HW has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.