新基因LINC01021作为p53靶基因的鉴定及其参与结肠癌发生发展的机制与临床意义研究

LINC01021 is one of several novel tumor associated genes identified by our group, and we have applied for a patent regarding its application in cancer diagnosis (Appl. No. 201610107412.4). After a series of tortuous preliminary investigation, we surprisingly found that: LINC01021 belongs to the category of long non-coding RNA (lncRNA) gene, the typical tumor suppressor directly transactivates its transcription, its expression is significantly down regulated and correlated with prognosis in several types of cancers including colon cancer, and its ectopic overexpression remarkably inhibits the proliferation of cancer cells. Based on those findings, we proposed that this novel lncRNA gene, LINC01021, is a novel direct p53 transcriptional target, and participates in the initiation and progression of cancers including colon cancer. In this project, by utilizing multiple transcriptional regulatory and molecular oncological techniques we are planning to further validate the direct transcriptional regulation of LINC01021 by p53, and deeply analyze the molecular mechanism and clinical significance of LINC01021 in the process of colon cancer development. The execution of this project will definitely verify our scientific hypothesis, increase our knowledge of the basic theory of tumor biology, evaluate the potential diagnostic and therapeutic values of LINC01021 in cancers especially colon cancer, and finally obtain the corresponding intellectual property rights.

LINC01021是我们前期在恶性肿瘤相关新基因挖掘筛选中获得的数个新基因之一，我们已对其用途申请了国家发明专利（专利号：201610107412.4）。经过一系列曲折的预实验探索，我们发现：其属于长链非编码RNA类基因；且经典抑癌蛋白p53可直接调控其转录；其表达在结肠癌等肿瘤中显著下调且与患者预后显著相关；其外源过表达可显著抑制结肠癌等癌细胞增殖。我们由此提出学术猜想：“新基因LINC01021是一个新的受p53直接调控的长链非编码RNA类基因，抑制结肠癌等恶性肿瘤发生发展”。本项目拟在此基础上，综合采用多种转录调控及分子肿瘤学研究技术，证实p53对LINC01021基因的直接转录调控效应，并深入分析其参与结肠癌等肿瘤发生发展的作用机制与临床意义。由此证明我们的学术猜想，丰富和拓展肿瘤生物学基础理论，并初步评价其在结肠癌等恶性肿瘤分子诊断和靶向治疗中的潜在应用价值，获取相应的知识产权。

肿瘤相关新基因的鉴定与功能解析及其知识产权猎取是后基因组时代国际竞争的一个焦点。LINC01021是我们前期在恶性肿瘤相关新基因挖掘筛选中获得的数个新基因之一。经过近三年曲折探索，我们发现：其属于长链非编码RNA类基因；经典抑癌蛋白p53可直接调控其转录；其表达在结肠癌等肿瘤中显著下调且与预后相关；其外源过表达可显著抑制癌细胞增殖。我们由此提出学术猜想：“新基因LINC01021是一个新的受p53直接调控的长链非编码RNA类基因，参与结肠癌等恶性肿瘤发生发展”。本项目在此基础上，综合采用多种转录调控及分子肿瘤学研究技术，证实p53对LINC01021基因的直接转录调控效应，并深入分析其参与结肠癌等肿瘤发生发展的作用机制与临床意义。证明了我们的学术猜想，并初步评价其在结肠癌等恶性肿瘤分子诊断和靶向治疗中的潜在应用价值。