Department of Hematology, The Fifth Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, China.
Department of Hematology, Henan Cancer Hospital , Zhengzhou, Henan, China.
Cell Cycle. 2020 Dec;19(23):3289-3302. doi: 10.1080/15384101.2020.1839701. Epub 2020 Nov 1.
Circular RNAs (circRNAs) possess important regulatory effects on multiple myeloma (MM) progression. Here, we aimed at exploring the function of circ_0007841 in MM and the underlying molecular mechanism. Expression of circ_0007841, microRNA (miR)-129-5p and Jagged1 (JAG1) was determined via qRT-PCR or western blot assay. Methyl thiazolyl tetrazolium (MTT) assay was applied to examine cell viability and IC50 value of MM cells to bortezomib (BTZ). Colony formation assay was performed to analyze cell proliferation. Moreover, cell apoptosis was assessed by flow cytometry and western blot analysis. Cell metastasis was evaluated by wound healing assay and Transwell assay. Function of circ_0007841 was determined by xenograft tumor assay. Target relationship between miR-129-5p and circ_0007841 or JAG1 was confirmed via dual-luciferase reporter, RNA immunoprecipitation (RIP) and pull-down assays. The up-regulation of circ_0007841 and JAG1, and the down-regulation of miR-129-5p were detected in MM bone marrow aspirates and cells. Circ_0007841 knockdown significantly repressed cell proliferation, chemoresistance, and metastasis, while contributed to apoptosis of MM cells , and reduced tumor growth . Circ_0007841 targeted miR-129-5p, and miR-129-5p inhibition reversed impact of silencing of circ_0007841 on MM cells. JAG1 was a mRNA target of miR-129-5p, whose overexpression could undermine the miR-129-5p-mediated effects on MM cells. Circ_0007841 positively regulated JAG1 expression via absorbing miR-129-5p. Circ_0007841 knockdown inhibited MM cell proliferation, metastasis and chemoresistance through modulating miR-129-5p/JAG1 axis, suggesting that circ_0007841 might serve as a potential therapeutic target of MM.
环状 RNA（circRNAs）对多发性骨髓瘤（MM）的进展具有重要的调节作用。在这里，我们旨在探索 circ_0007841 在 MM 中的功能及其潜在的分子机制。通过 qRT-PCR 或 Western blot 检测 circ_0007841、microRNA（miR）-129-5p 和 Jagged1（JAG1）的表达。采用甲基噻唑基四唑（MTT）测定法检测 MM 细胞活力和硼替佐米（BTZ）的 IC50 值。通过集落形成实验分析细胞增殖。此外，通过流式细胞术和 Western blot 分析评估细胞凋亡。通过划痕愈合实验和 Transwell 实验评估细胞转移。通过异种移植肿瘤实验确定 circ_0007841 的功能。通过双荧光素酶报告、RNA 免疫沉淀（RIP）和下拉实验证实 miR-129-5p 与 circ_0007841 或 JAG1 之间的靶关系。在 MM 骨髓抽吸物和细胞中检测到 circ_0007841 和 JAG1 的上调以及 miR-129-5p 的下调。circ_0007841 敲低显著抑制 MM 细胞的增殖、化疗耐药性和转移，同时促进 MM 细胞的凋亡，并减少肿瘤生长。circ_0007841 靶向 miR-129-5p，抑制 circ_0007841 沉默对 MM 细胞的影响可以被 miR-129-5p 的抑制所逆转。JAG1 是 miR-129-5p 的 mRNA 靶标，其过表达可以破坏 miR-129-5p 对 MM 细胞的影响。circ_0007841 通过吸收 miR-129-5p 正向调节 JAG1 表达。circ_0007841 敲低通过调节 miR-129-5p/JAG1 轴抑制 MM 细胞增殖、转移和化疗耐药性，表明 circ_0007841 可能成为 MM 的潜在治疗靶点。
