Arab Imene, Lim Su-Geun, Suk Kyoungho, Lee Won-Ha
School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
Cells. 2024 Dec 8;13(23):2027. doi: 10.3390/cells13232027.
Long intergenic noncoding (LINC)01270 is a 2278 bp transcript belonging to the intergenic subset of long noncoding (lnc)RNAs. Despite increased reports of LINC01270's involvement in different diseases, evident research on its effects on inflammation is yet to be achieved. In the present study, we investigated the potential role of LINC01270 in modulating the inflammatory response in the human monocytic leukemia cell line THP-1. Lipopolysaccharide treatment upregulated LINC01270 expression, and siRNA-mediated suppression of LINC01270 enhanced NF-κB activity and the subsequent production of cytokines IL-6, IL-8, and MCP-1. Interestingly, the knockdown of LINC01270 downregulated expression of leucine zipper downregulated in cancer 1 (LDOC1), a novel NF-κB suppressor. An analysis of the LINC01270/micro-RNA (miRNA)/protein interactome profile identified miR-326 as a possible mediator. Synthetic RNA agents that perturb the interaction among LINC01270, miR-326, and LDOC1 mRNA mitigated the changes caused by LINC01270 knockdown in THP-1 cells. Additionally, a luciferase reporter assay in HEK293 cells further confirmed that LINC01270 knockdown enhances NF-κB activation, while its overexpression has the opposite effect. This study provides insight into LINC01270's role in modulating inflammatory responses to lipopolysaccharide stimulation in THP-1 cells via the miR-326/LDOC1 axis, which negatively regulates NF-κB activation.
长链基因间非编码RNA（LINC）01270是一个2278碱基对的转录本，属于长链非编码（lnc）RNA的基因间子集。尽管关于LINC01270参与不同疾病的报道越来越多，但其对炎症影响的显著研究尚未完成。在本研究中，我们调查了LINC01270在调节人单核细胞白血病细胞系THP-1炎症反应中的潜在作用。脂多糖处理上调了LINC01270的表达，而siRNA介导的LINC01270抑制增强了NF-κB活性以及随后细胞因子IL-6、IL-8和MCP-1的产生。有趣的是，LINC01270的敲低下调了癌症1中下调的亮氨酸拉链（LDOC1）的表达，LDOC1是一种新型的NF-κB抑制剂。对LINC01270/微小RNA（miRNA）/蛋白质相互作用组图谱的分析确定miR-326为可能的介导因子。扰乱LINC01270、miR-326和LDOC1 mRNA之间相互作用的合成RNA试剂减轻了THP-1细胞中LINC01270敲低引起的变化。此外，在HEK293细胞中进行的荧光素酶报告基因检测进一步证实，LINC01270敲低增强了NF-κB激活，而其过表达则具有相反的效果。本研究揭示了LINC01270通过miR-326/LDOC1轴在调节THP-1细胞对脂多糖刺激的炎症反应中的作用，该轴负向调节NF-κB激活。
