Lrrc75a,也称为LRRC75A,是一种存在于人体中的基因,其编码的蛋白质在多种生物学过程中发挥作用。LRRC75A属于富含亮氨酸重复序列(leucine-rich repeat-containing)蛋白家族,这类蛋白在细胞信号传导、细胞骨架组织、细胞粘附和细胞凋亡等方面发挥着重要作用。LRRC75A的具体功能尚不完全清楚,但已有研究表明,该基因在多种疾病的发生发展中起着关键作用。
根据现有的研究,LRRC75A在多种肿瘤中表现出异常表达,包括多发性骨髓瘤、宫颈癌、结直肠癌、乳腺癌和肾细胞癌等。例如,研究发现,LRRC75A-AS1(LRRC75A的反义RNA1)在多发性骨髓瘤细胞中高表达,并通过靶向miR-199b-5p/PDCD4轴抑制多发性骨髓瘤的生长[1]。在宫颈癌中,LRRC75A-AS1通过结合IGF2BP1并抑制SYVN1介导的NLRP3泛素化来促进上皮-间质转化(EMT),从而促进宫颈癌的进展[2]。在结直肠癌中,LRRC75A-AS1的表达水平较低,并且其下调可以促进结直肠癌细胞的增殖和迁移[3]。
LRRC75A还与血管生成相关。研究发现,LRRC75A在缺血性条件下骨髓间充质干细胞(MSCs)中高表达,并且LRRC75A的表达水平与血管内皮生长因子(VEGF)的分泌相关[4]。此外,LRRC75A还参与调节巨噬细胞的极化和先天免疫反应,LRRC75A-AS1和GAPLINC在巨噬细胞中下调可以降低巨噬细胞的极化标记物表达,并影响巨噬细胞的吞噬、抗原处理和炎症因子分泌[5]。
LRRC75A还与血管钙化相关。研究发现,LRRC75A-AS1在血管平滑肌细胞(VSMCs)中表达,并且LRRC75A-AS1的敲低可以促进VSMCs的钙化,而LRRC75A-AS1的过表达可以抑制VSMCs的钙化[6]。此外,LRRC75A-AS1还可以通过下调成骨细胞相关因子的表达来抑制VSMCs的钙化[6]。
综上所述,LRRC75A在多种生物学过程中发挥着重要作用,包括肿瘤发生发展、血管生成、巨噬细胞极化和血管钙化等。LRRC75A的异常表达与多种疾病的发生发展相关,因此LRRC75A有望成为疾病诊断和治疗的潜在靶点。
参考文献:
1. Pang, Quantang, Wang, Yanyan, Bi, Dapeng, Lu, Hongyu. 2020. LRRC75A-AS1 targets miR-199b-5p/PDCD4 axis to repress multiple myeloma. In Cancer biology & therapy, 21, 1051-1059. doi:10.1080/15384047.2020.1831373. https://pubmed.ncbi.nlm.nih.gov/33131397/
2. Sui, Hongying, Shi, Caixia, Yan, Zhipeng, Man, Lin, Wang, Fang. . LRRC75A-AS1 Drives the Epithelial-Mesenchymal Transition in Cervical Cancer by Binding IGF2BP1 and Inhibiting SYVN1-Mediated NLRP3 Ubiquitination. In Molecular cancer research : MCR, 22, 1075-1087. doi:10.1158/1541-7786.MCR-23-0478. https://pubmed.ncbi.nlm.nih.gov/38180377/
3. Chen, Jianxiong, Lan, Jiawen, Ye, Zhiwei, Zou, Ying, Zhou, Jun. 2019. Long noncoding RNA LRRC75A-AS1 inhibits cell proliferation and migration in colorectal carcinoma. In Experimental biology and medicine (Maywood, N.J.), 244, 1137-1143. doi:10.1177/1535370219874339. https://pubmed.ncbi.nlm.nih.gov/31505952/
4. Miura, Takumi, Kouno, Tsukasa, Takano, Megumi, Kawai, Jun, Sato, Yoji. . Single-Cell RNA-Seq Reveals LRRC75A-Expressing Cell Population Involved in VEGF Secretion of Multipotent Mesenchymal Stromal/Stem Cells Under Ischemia. In Stem cells translational medicine, 12, 379-390. doi:10.1093/stcltm/szad029. https://pubmed.ncbi.nlm.nih.gov/37263619/
5. Valverde, Araceli, Naqvi, Raza Ali, Naqvi, Afsar R. 2024. Macrophage-enriched novel functional long noncoding RNAs LRRC75A-AS1 and GAPLINC regulate polarization and innate immune responses. In Inflammation research : official journal of the European Histamine Research Society ... [et al.], 73, 771-792. doi:10.1007/s00011-024-01865-w. https://pubmed.ncbi.nlm.nih.gov/38592458/
6. Jeong, Geon, Kwon, Duk-Hwa, Shin, Sera, Kook, Hyun, Kim, Young-Kook. 2019. Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification. In Scientific reports, 9, 5848. doi:10.1038/s41598-019-42283-x. https://pubmed.ncbi.nlm.nih.gov/30971745/