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环状 RNA 转录激活因子通过 miR-324-5p 依赖调控 HGF 促进多发性骨髓瘤进展。

CircATIC Contributes to Multiple Myeloma Progression via miR-324-5p-Dependent Regulation of HGF.

机构信息

Department of Orthopedics, ShangRao People's Hospital, Shangrao, China.

Department of Pharmacology, Jiangxi Medical College, Jiangnan Garden, Shuinan street, Xinzhou District, Shangrao, 334000, Jiangxi, China.

出版信息

Biochem Genet. 2022 Dec;60(6):2515-2532. doi: 10.1007/s10528-022-10228-1. Epub 2022 May 17.

Abstract

Circular RNA (circRNA) 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (circATIC; hsa_circ_0058058) was observed to be upregulated in multiple myeloma (MM) by former article. However, the function and exact mechanism of circATIC in MM development remain barely known. CircRNA-microRNA (miRNA)-messenger RNA (mRNA) axis was established through using bioinformatic databases (starbase, Circinteractome, and microT-CDS). Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA-pull down assay were utilized to verify the target relationship between microRNA-324-5p (miR-324-5p) and circATIC or hepatocyte growth factor (HGF). CircATIC expression was upregulated in MM patients and cell lines. CircATIC interference notably hampered cell proliferation, migration, invasion, and glycolysis and induced cell apoptosis of MM cells. MiR-324-5p was a target of circATIC. CircATIC silencing-mediated effects in MM cells were largely overturned by the knockdown of miR-324-5p. HGF was a target of miR-324-5p, and circATIC upregulated the expression of HGF partly through sponging miR-324-5p in MM cells. MiR-324-5p suppressed the malignant behaviors of MM cells, which were largely counteracted by the overexpression of HGF in MM cells. CircATIC accelerated the proliferation, migration, invasion, and glycolysis and suppressed the apoptosis of MM cells through mediating miR-324-5p/HGF signaling.

摘要

环状 RNA (circRNA) 5-氨基咪唑-4-甲酰胺核苷酸(formyltransferase/IMP)环水解酶 (circATIC; hsa_circ_0058058)在前一篇文章中被观察到在多发性骨髓瘤 (MM) 中上调。然而,circATIC 在 MM 发展中的功能和确切机制仍知之甚少。通过使用生物信息学数据库 (starbase、Circinteractome 和 microT-CDS) 建立了环状 RNA-微小 RNA (miRNA)-信使 RNA (mRNA) 轴。双荧光素酶报告基因检测、RNA 免疫沉淀检测和 RNA 下拉检测用于验证微小 RNA-324-5p (miR-324-5p) 与 circATIC 或肝细胞生长因子 (HGF) 之间的靶关系。circATIC 在 MM 患者和细胞系中表达上调。circATIC 干扰显著抑制 MM 细胞的增殖、迁移、侵袭和糖酵解,并诱导细胞凋亡。miR-324-5p 是 circATIC 的靶标。circATIC 沉默介导的 MM 细胞效应在很大程度上被 miR-324-5p 的敲低所逆转。HGF 是 miR-324-5p 的靶标,circATIC 通过在 MM 细胞中海绵吸附 miR-324-5p 来部分上调 HGF 的表达。miR-324-5p 抑制 MM 细胞的恶性行为,而在 MM 细胞中过表达 HGF 则在很大程度上拮抗了这一作用。circATIC 通过介导 miR-324-5p/HGF 信号通路加速 MM 细胞的增殖、迁移、侵袭和糖酵解,并抑制细胞凋亡。

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