LncRNA-17519在脑膜瘤恶变中的作用及其作为临床标志物的研究

Malignant meningioma is prone to relapse after excision due to its aggressive growth. Our preliminary study showed that LncRNA-17519 is significantly positively correlated with the malignant transformation degree of meningioma. Clinical data suggest that no abnormal expression of LncRNA-17519 exists in common tumor tissues from lung cancer, liver cancer, colorectal cancer and gastric cancer. Basic study data suggest: (1) LncRNA-17519 knockdown significantly inhibited the proliferation, invasion and migration of meningioma cells, in which the expression regulation of KLF4 gene was involved; (2) Four LncRNA-17519-minis sequences can be detected in the serum from meningioma patients, and both ends of each sequence contain a seed sequence of miRNA-148a/b-3p and miRNA-152-3p. Therefore, LncRNA-17519-minis has the potential to be a diagnosis marker for meningioma. The main purpose of the study is to search for a complete theoretical foundation for using LncRNA-17519-minis as a clinic marker, improve clinical examination approaches of LncRNA-17519-minis and establish an evaluation system for using it as clinical diagnosis marker for meningioma, based on in-depth investigation on the mechanism through which LncRNA-17519 regulates the malignant transformation of meningioma.

恶性脑膜瘤呈侵袭性生长，导致切除后极易复发。本课题组前期临床研究证实：LncRNA-17519与脑膜瘤恶变程度显著正相关；肺癌、肝癌、结直肠癌、胃癌等肿瘤组织中均未检测到LncRNA-17519的异常表达。同时发现：LncRNA-17519敲减可以明显抑制脑膜瘤细胞的增殖，侵袭及迁移，这与其对KLF4基因的表达调控有关；脑膜瘤患者血清中可以检测到四条LncRNA-17519-minis序列，这四条检出序列两端均具有miRNA-148a/b-3p或miRNA-152-3p的种子区。因此，LncRNA-17519-minis具有作为脑膜瘤临床诊断标志物的潜力。本课题在深入研究LncRNA-17519调控脑膜瘤恶变机制的基础上，为LncRNA-17519-minis做为临床标志物寻找完整理论基础，完善针对LncRNA-17519-minis的临床检测手段，建立其作为脑膜瘤临床诊断标志物的评价体系

恶性脑膜瘤具有进展快、侵袭性强、预后差的特点，手术摘除后极易复发，放化疗效果欠佳，如何早期诊断并有效治疗恶性脑膜瘤是临床上尚未解决的重要问题。长链非编码RNA（lncRNA）近年来发现在多种肿瘤的发生发展中发挥了重要作用。本课题组通过高通量筛选出在脑膜瘤中差异表达的lncRNA，其中RT-qPCR验证lncRNA-17519在恶性脑膜瘤组织中高表达，并与脑膜瘤恶变程度显著正相关，lncRNA-17519作为miRNA-148a-3p的“分子海绵”，影响其下游抑癌基因KLF4的表达，发挥促进脑膜瘤恶变的功能。LncRNA-17519敲减可以明显抑制脑膜瘤细胞的增殖、侵袭及迁移，并抑制皮下荷瘤小鼠瘤体的生长和体积，延长生存期。因此体内外实验表明，lncRNA-17519具有作为脑膜瘤临床诊断、治疗和预后标志物的潜力。