长链非编码RNA LINC00472在肺腺癌发生发展中的抑癌作用及其机制研究

New therapeutic strategies are urgently needed for lung cancer，a kind of high degree malignancy and poor prognosis cancer type.Recently found LncRNA abnormal expression plays an important role in many kinds of malignant tumors.Our previous studies have revealed that LncRNA-LINC00472 was significantly down-regulated in non-small cell lung cancer tissues compared to adjacent normal tissues for the first time.Functional study proved that over-expression of LINC00472 inhibited the proliferation and invasion ability of lung adenocarcinoma cell line,suggesting that LINC00472 was a potential tumor suppression LncRNA in lung adenocarcinoma.In future research,we planned to characterize the role of LINC00472 in growth,migration and invasion ability of lung adenocarcinoma cell line both in vitro and vivo.In order to clarify the suppressor molecule mechanism of LINC00472,We planned to use RNA-pull down and RIP techniques to screen for the specific proteins binding to LINC00472.Using RNA-Seq to identification its downstream target genes and regulated transduction pathways. The results will provide a new idea for the role of LncRNA in development, invasion and metastasis of lung adenocarcinoma, and provide a new theoretical and experimental basis for the treatment of lung adenocarcinoma.

肺癌恶性程度高、预后差，迫切需要新型治疗策略。近来发现LncRNA异常表达在多种恶性肿瘤中发挥重要作用，是目前的研究热点。我们前期通过对肺癌临床样本进行筛选发现LncRNA-LINC00472在肿瘤组织中呈现异常低表达，通过克隆LINC00472全长并将其过表达于肺癌细胞系，发现LINC00472能够抑制肺腺癌细胞生长、增殖和侵袭能力，提示其在肺腺癌中发挥潜在的抑癌功能。本项目拟进一步研究LINC00472在肺腺癌增殖、侵袭及放、化疗抵抗中的抑癌功能。利用RNA-pull down及RIP技术鉴定LINC00472的特异性结合蛋白，RNA-Seq技术鉴定其调控的下游靶基因，阐明其抑癌分子机制。本项目为LncRNA在肺腺癌发生发展与侵袭转移中所起到的作用提供新的思路，并为肺腺癌的治疗策略提供新的理论和实验依据。

肺癌（Lung Cancer, LC）是目前最常见、致死率最高的恶性肿瘤，其总体五年生存率低于20%。探讨肺癌发生发展过程分子机制，开发新的肿瘤分子标志物，意义重大。本项目研究了LINC00472在肺腺癌中的差异表达量，并研究其在肺腺癌的增殖、侵袭及放、化疗抵抗中的抑癌功能。利用RNA-pull down及RIP技术鉴定LINC00472的特异性结合蛋白，RNA-Seq技术鉴定其调控的下游靶基因，阐明其抑癌分子机制。我们对肺癌临床样本进行筛选发现LncRNA-LINC00472在肿瘤组织中呈现异常低表达，通过克隆LINC00472全长并将其过表达于肺癌细胞系，发现LINC00472能够抑制肺腺癌细胞生长、增殖和侵袭能力。进一步研究发现G3BP1能够与p53 结合从而将其阻滞于胞浆中，LINC00472能够与G3BP1 结合，从而竞争性地减少p53与G3BP1的结合，降低G3BP1对p53 的阻滞，导致p53 入核引发肺腺癌等癌细胞的凋亡和铁死亡。本项目为LncRNA在肺腺癌发生发展与侵袭转移中所起到的作用提供新的思路，并为肺腺癌的治疗策略提供新的理论和实验依据。