Sun Shu-Wen, Chen Yan, Liao Hui-Juan, Zhang Wei, Xu Wen-Ming, He Guo-Qian
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Evid Based Complement Alternat Med. 2022 Jun 24;2022:9100056. doi: 10.1155/2022/9100056. eCollection 2022.
To analyze the mechanism of LINC00461 regulating the recurrence of diffuse large B cell lymphoma (DLBCL) through microRNA (miR)-411-5p/BCL2 interacting protein 3 (BNIP3) pathway.
DLBCL samples in TCGA and GSE12453 were used for differential analysis to find long noncoding RNA (lncRNA) related to DLBCL recurrence. The 4 DLBCL data with the highest and lowest expression levels of LINC00461 in the TCGA database were selected for GSEA enrichment analysis. The targeting relationships of miR-411-5p with LINC00461 and BNIP3 were verified by the dual luciferase report. Blood samples from DLBCL patients were used to analyze the correlation between miR-411-5p and LINC00461 or BNIP3. LINC00461, miR-411-5p, or BNIP3 was overexpressed or silenced by transfection, and a tumor-bearing nude mice model was constructed to detect their effects on proliferation and apoptosis.
The level of LINC00461 in DLBCL was significantly higher than that in normal cases, and the level in recurrence DLBCL was significantly higher than that in nonrecurrence. The enrichment analysis results showed that the function of LINC00461 was closely related to apoptosis. The results shown that miR-411-5p bound to LINC00461 and BNIP3 and was negatively correlated with LINC00461 and BNIP3 mRNA in blood of DLBCL patients. Suppressing the level of LINC00461 inhibited cell proliferation and induced apoptosis. The inhibition of LINC00461 or overexpression of miR-411-5p reduced the expression of BNIP3 protein, thereby inducing apoptosis at the in vivo and in vitro levels.
LINC00461 may induce miR-411-5p to "sponge," thereby increasing the expression of BNIP3 protein, and exerting the function of inhibiting apoptosis and promoting DLBCL recurrence.
分析长链非编码RNA 00461（LINC00461）通过微小RNA（miR）-411-5p/BCL2相互作用蛋白3（BNIP3）通路调控弥漫性大B细胞淋巴瘤（DLBCL）复发的机制。
利用癌症基因组图谱（TCGA）数据库和基因表达综合数据库（GSE）12453中的DLBCL样本进行差异分析，以寻找与DLBCL复发相关的长链非编码RNA（lncRNA）。在TCGA数据库中选取LINC00461表达水平最高和最低的4个DLBCL数据进行基因集富集分析（GSEA）。通过双荧光素酶报告实验验证miR-411-5p与LINC00461和BNIP3的靶向关系。采集DLBCL患者的血液样本，分析miR-411-5p与LINC00461或BNIP3之间的相关性。通过转染过表达或沉默LINC00461、miR-411-5p或BNIP3，并构建荷瘤裸鼠模型，检测它们对细胞增殖和凋亡的影响。
DLBCL中LINC00461的水平显著高于正常病例，复发DLBCL中的水平显著高于未复发者。富集分析结果显示，LINC00461的功能与细胞凋亡密切相关。结果表明，miR-411-5p与LINC00461和BNIP3结合，且在DLBCL患者血液中与LINC00461和BNIP3 mRNA呈负相关。抑制LINC00461的水平可抑制细胞增殖并诱导凋亡。抑制LINC00461或过表达miR-411-5p可降低BNIP3蛋白的表达，从而在体内和体外水平诱导细胞凋亡。
LINC00461可能诱导miR-411-5p发挥“海绵”作用，从而增加BNIP3蛋白的表达，发挥抑制细胞凋亡和促进DLBCL复发的作用。
