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Systematic analysis of genes involved in oral cancer metastasis to lymph nodes

100%

Zhang X., Zhang T., Tang X., Lin Y., Han X., Wang H., Ming H., Liu K., Feng G.

Cellular and Molecular Biology Letters

2018

tom 23

Oral cancer remains a deadly disease worldwide. Lymph node metastasis and invasion is one of the causes of death from oral cancer. Elucidating the mechanism of oral cancer lymph node metastasis and identifying critical regulatory genes are important for the treatment of this disease. This study aimed to identify differentially expressed genes (gene signature) and pathways that contribute to oral cancer metastasis to lymph nodes. The GSE70604-associated study compared gene profiles in lymph nodes with metastasis of oral cancer to those of normal lymph nodes. The GSE2280-associated study compared gene profiles in primary tumor of oral cancer with lymph node metastasis to those in tumors without lymph node metastasis. There are 28 common differentially expressed genes (DEGs) showing consistent changes in both datasets in overlapping analysis. GO biological process and KEGG pathway analysis of these 28 DEGs identified the gene signature CCND1, JUN and SPP1, which are categorized as key regulatory genes involved in the focal adhesion pathway. Silencing expression of CCND1, JUN and SPP1 in the human oral cancer cell line OECM-1 confirmed that those genes play essential roles in oral cancer cell invasion. Analysis of clinical samples of oral cancer found a strong correlation of these genes with short survival, especially JUN expression associated with metastasis. Our study identified a unique gene signature – CCND1, JUN and SPP1 – which may be involved in oral cancer lymph node metastasis.

Missense mutations in IHH impair Indian hedgehog signaling in C3H10T1-2 cells: implications for brachydactyly type A1, and new targets for hedgehog signaling

81%

Guo S., Zhou J., Gao B., Hu J., Wang H., Meng J., Zhao X., Ma G., Lin C., Xiao Y., Tang W., Zhu X., Cheah K. S. E., Feng G., Chan D., He L.

Cellular and Molecular Biology Letters

2010

tom 15

nr 1

153-176

Heterozygous missense mutations in IHH result in Brachydactyly type A1 (BDA1; OMIM 112500), a condition characterized by the shortening of digits due to hypoplasia/aplasia of the middle phalanx. Indian Hedgehog signaling regulates the proliferation and differentiation of chondrocytes and is essential for endochondral bone formation. Analyses of activated IHH signaling in C3H10T1/2 cells showed that three BDA1-associated mutations (p.E95K, p.D100E and p.E131K) severely impaired the induction of targets such as Ptch1 and Gli1. However, this was not a complete loss of function, suggesting that these mutations may affect the interaction with the receptor PTCH1 or its partners, with an impact on the induction potency. From comparative microarray expression analyses and quantitative real-time PCR, we identified three additional targets, Sostdc1, Penk1 and Igfbp5, which were also severely affected. Penk1 and Igfbp5 were confirmed to be regulated by GLI1, while the induction of Sostdc1 by IHH is independent of GLI1. SOSTDC1 is a BMP antagonist, and altered BMP signaling is known to affect digit formation. The role of Penk1 and Igfbp5 in skeletogenesis is not known. However, we have shown that both Penk1 and Igfbp5 are expressed in the interzone region of the developing joint of mouse digits, providing another link for a role for IHH signaling in the formation of the distal digits.

The relationship between liver dysfunction and arsenic methylation in Mice

81%

Li S., Ma R., Niu Q., Xu S., Pang L., Ding Y., Mu L., Jing M., Feng G., Liu J. M., Wang H., Li F., Guo S.

Polish Journal of Environmental Studies

2015

tom 24

nr 4

The different methyl metabolic products of inorganic arsenic lead to various toxicities. Arsenic has been demonstrated to induce hepatotoxicity by oxidative stress. The relationship between hepatic injury and inorganic methylation is not yet known. This study was designed to explore the relationship between arsenic methylation and liver oxidative stress induced by arsenic trioxide (ATO). Forty healthy KM mice were randomly divided into control group (0.9% saline) and As₂O₃ (1.0 mg/Kg/day, 2.0 mg/Kg/day, 4.0 mg/Kg/day) groups with gastric perfusion for five weeks using high-efficiency liquid chromatography and hydride genesis atomic fluorescence spectroscopy (HPLC-HGAFS). The products of arsenic trioxiode methylating, including trivalent inorganic arsenic (iAs³⁺), pentavalent inorganic arsenic (iAs⁵⁺), mono methyl arsenic (MMA), and dimethyl arsenic (DMA) in the liver were determined. The indexes of arsenic methylation, including primary methyl index (PMI) and second methyl index (SMI) were calculated. The level of hepatic function and activity of MDA, GSH, SOD, and TAOC were detected with kits. We found that the remaining arsenic metabolic products in liver significantly increased with the increasing doses of arsenic trioxide and the liver function and oxidative stress deteriorated. Negative correlations were found between MMA%, PMI and GSH, SOD, and TAOC, while DMA% and SMI positively correlated with the levels of ALT and AST. PMI and SMI negatively correlated with TAOC, GSH, SOD, ALT, and AST, positively linked with the level of MDA. The present study demonstrates that the hepatotoxicity induced by the arsenic accounts for deteriorating oxidative injury activized by arsenic methylation metabolism, providing additional evidence to suggest a mechanism of arsenic poisoning. Therefore, reducing the process of arsenic methylation may be potentially benefical in treating and – more importantly – preventing arseniasis.

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Systematic analysis of genes involved in oral cancer metastasis to lymph nodes

Missense mutations in IHH impair Indian hedgehog signaling in C3H10T1-2 cells: implications for brachydactyly type A1, and new targets for hedgehog signaling

The relationship between liver dysfunction and arsenic methylation in Mice