Li Xiayu, Shen Shourong, Wu Minghua, Li Xiaoling, Xiong Wei, Lu Jianhong, Zhou Ming, Ma Jian, Xiang Juanjuan, Zeng Zhaoyang, Xiang Bo, Zhou Yanhong, Xiao Lan, Zhou Houde, Fan Songqing, Li Guiyuan
Disease Genomic Research Center, Central South University, Changsha 410078, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Jul;36(7):585-91. doi: 10.3969/j.issn.1672-7347.2011.07.001.
The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.
中国国家重点科研项目“不同阶段多基因肿瘤的转录组调控及分子机制研究”的科研团队，聚焦于4种常见多基因肿瘤的转录组学领域，包括鼻咽癌（NPC）、乳腺癌、结直肠癌和神经胶质瘤。已针对肿瘤转录组学的表达与调控、肿瘤抑制/易感基因的鉴定、包括微小RNA（miRNAs）在内的肿瘤表观遗传学机制，以及肿瘤转录组学与蛋白质组学的特定基因/蛋白质簇的比较研究，开展了广泛的实验室工作。已鉴定出包括SPLUNC1、LTF、BRD7、NOR1、BRCA1/2、PALB2、AF1Q、SOX17、NGX6、SOX7和LRRC4等基因，为肿瘤起始和侵袭阶段的关键转录调控基因。相应地，“SPLUNC1-miR-141-靶基因”的鼻咽癌基因信号调控网络、“miR-193b-uPA”的乳腺癌相互作用信号通路、“miR-381-LRRC4-MEK/ERK/AKT”的神经胶质瘤信号网络，以及结直肠癌转移相关基因NGX6的微小RNA-靶基因网络，均已得到透彻阐明。这些丰硕成果表明，关键信号通路中关键分子的变化，将导致多基因肿瘤信号转导和基因调控网络出现严重功能障碍，这表明在发病机制类别中，这些肿瘤可能进一步归类为“基因信号转导和基因调控网络紊乱疾病”。这些研究为揭示不同阶段多基因肿瘤的分子机制和转录组调控奠定了坚实基础。
