T淋巴母细胞淋巴瘤/白血病(T-LBL/ALL)化疗耐药是病人复发死亡的主要原因。长链非编码RNA在T-LBL/ALL化疗耐药中起到重要作用，但机理不清楚。我们前期体内外实验发现，高表达LINC00630能够提高 T-LBL/ALL的化疗耐药性；我们还发现提高miR-103a-3p/miR-335-5p的表达水平能够降低LINC00630诱导的化疗耐药性。由此，我们提出：LINC00630以ceRNA的形式“吸附”互补的miR-103a-3p/miR-335-5p，导致miR-103a-3p/miR-335-5p对下游靶基因转录后抑制作用减弱，激活下游相关信号通路，提高肿瘤细胞的化疗耐药性。本项目拟通过一系列体内外实验阐明LINC00630、miR-103a-3p/miR-335-5p及下游靶基因对T-LBL/ALL化疗耐药调控网络和分子机理，为开发新型靶向药物提供客观基础。

Clinically, T-lymphoblastic lymphoma/leukemia (T-LBL/ALL) chemotherapy resistance is the main cause of relapse and T-LBL/ALL-related death. Long non-coding RNA plays an important role in T-LBL/ALL chemotherapy resistance, but the underling mechanism remains unclear. Recently, we identified that LINC00630 was overexpressed in T-LBL/ALL tissues and correlated with T-LBL/ALL patients’ chemotherapy resistance by using LncRNA microarray analysis. Functional study demonstrated overexpression of LINC00630 could enhance drug resistance of T-LBL/ALL cells. Luciferase assay confirmed that miR-103a-3p/miR-335-5p was the target sequence of LINC00630. Increasing the expression of miR-103a-3p/miR-335-5p can reduce the drug resistance induced by LINC00630. Therefore, we propose the new mechanism that LINC00630 modulated miR-103a-3p/miR-335-5p expression as the form of ceRNA, decrease the inhibitory effect of miR-103a-3p/miR-335-5p on target genes and downstream signaling pathways, and finally, promote T-LBL/ALL chemotherapy resistance. This study is aimed at exploring the molecular functions and clinical value of LINC00630, miR-103a-3p/miR-335-5p and downstream target genes in promoting chemotherapy resistance, and providing experimental research basis for revealing the precise mechanism of drug resistance, so as to find novel therapeutic targets and develop new modalities of treatment.