Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli "Federico II", Naples, Italy.
PLoS One. 2014 May 27;9(5):e98295. doi: 10.1371/journal.pone.0098295. eCollection 2014.
We have previously shown that the expression of CBX7 is drastically decreased in several human carcinomas and that its expression progressively decreases with the appearance of a highly malignant phenotype. The aim of our study has been to investigate the mechanism by which the loss of CBX7 expression may contribute to the emergence of a more malignant phenotype.
We analyzed the gene expression profile of a thyroid carcinoma cell line after the restoration of CBX7 and, then, analyzed the transcriptional regulation of identified genes. Finally, we evaluated the expression of CBX7 and regulated genes in a panel of thyroid and lung carcinomas.
We found that CBX7 negatively or positively regulates the expression of several genes (such as SPP1, SPINK1, STEAP1, and FOS, FOSB, EGR1, respectively) associated to cancer progression, by interacting with their promoter regions and modulating their transcriptional activity. Quantitative RT-PCR analyses in human thyroid and lung carcinoma tissues revealed a negative correlation between CBX7 and its down-regulated genes, while a positive correlation was observed with up-regulated genes.
In conclusion, the loss of CBX7 expression might play a critical role in advanced stages of carcinogenesis by deregulating the expression of specific effector genes.
我们之前已经证明，CBX7 的表达在几种人类癌中显著降低，并且随着高度恶性表型的出现，其表达逐渐降低。我们研究的目的是探讨 CBX7 表达缺失如何导致更恶性表型的出现的机制。
我们分析了 CBX7 恢复后甲状腺癌细胞系的基因表达谱，然后分析了鉴定基因的转录调控。最后，我们评估了 CBX7 在一组甲状腺癌和肺癌中的表达和调节基因。
我们发现 CBX7 通过与它们的启动子区域相互作用并调节其转录活性，负调控或正调控与癌症进展相关的几个基因（如 SPP1、SPINK1、STEAP1 和 FOS、FOSB、EGR1）的表达。在人甲状腺和肺癌组织中的定量 RT-PCR 分析显示 CBX7 与下调基因之间呈负相关，而与上调基因之间呈正相关。
总之，CBX7 表达的丧失可能通过调节特定效应基因的表达在癌发生的晚期阶段发挥关键作用。
