环状 RNA circ_0048764 通过调控 microRNA-1296-5p/含三个结构域蛋白 14 轴促进乳腺癌的发展。
Circular RNA circ_0048764 promotes the development of breast cancer by regulating microRNA-1296-5p/tripartite motif containing 14 axis.
机构信息
Department of General Surgery, Xiangyang Central Hospital, Xiangyang, China.
出版信息
Bioengineered. 2022 Feb;13(2):1963-1974. doi: 10.1080/21655979.2021.1995990.
Breast cancer (BC) is one of the leading causes of cancer-related deaths in females. Circular RNA (circRNA), as reported, is involved in the progression of BC. This work focuses on clarifying the biological function of circ_0048764 in BC and its hidden mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of circ_0048764, microRNA-1296-5p (miR-1296-5p), and tripartite motif containing 14 (TRIM14) in BC tissues and cell lines. Besides, the status of proliferation, migration, invasion and apoptosis of BC cells was probed by cell counting kit-8 (CCK-8), EdU, transwell and flow cytometry assays. Western blot was adopted to examine the level of TRIM14 protein in BC cells. In addition, dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were conducted to corroborate the targeting relationships between miR-1296-5p and circ_0048764 or TRIM14. It was revealed that circ_0048764 expression was remarkably up-regulated in BC tissues and cells, and circ_0048764 expression was associated with TNM stage and tumor size. Functionally, overexpression of circ_0048764 significantly promoted BC cell proliferative, migrative and invasive abilities and inhibited apoptosis, while circ_0048764 knockdown exerted the opposite effects. Mechanistically, circ_0048764 directly targeted miR-1296-5p and could negatively modulate its expression in BC cells. Besides, miR-1296-5p could reverse the influence of circ_0048764 on BC viability, migration, invasion and apoptosis. Moreover, TRIM14 was confirmed to be a downstream target of miR-1296-5p. Circ_0048764 positively regulated TRIM14 expression in BC cells via targeting miR-1296-5p. Collectively, it is concluded that circ_0048764 promotes the development of BC via modulating the miR-1296-5p/TRIM14 axis.
乳腺癌(BC)是女性癌症相关死亡的主要原因之一。据报道,环状 RNA(circRNA)参与了 BC 的进展。这项工作旨在阐明 circ_0048764 在 BC 中的生物学功能及其潜在机制。通过定量实时聚合酶链反应(qRT-PCR)检测 BC 组织和细胞系中 circ_0048764、微小 RNA-1296-5p(miR-1296-5p)和三肽重复含 14 个(TRIM14)的表达。此外,通过细胞计数试剂盒-8(CCK-8)、EdU、Transwell 和流式细胞术检测 BC 细胞的增殖、迁移、侵袭和凋亡状态。通过 Western blot 检测 BC 细胞中 TRIM14 蛋白的水平。此外,进行双荧光素酶报告基因检测和 RNA 免疫沉淀(RIP)检测以证实 miR-1296-5p 与 circ_0048764 或 TRIM14 之间的靶向关系。结果表明,circ_0048764 在 BC 组织和细胞中表达显著上调,circ_0048764 表达与 TNM 分期和肿瘤大小有关。功能上,circ_0048764 的过表达显著促进了 BC 细胞的增殖、迁移和侵袭能力,并抑制了细胞凋亡,而 circ_0048764 的敲低则产生了相反的效果。机制上,circ_0048764 可直接靶向 miR-1296-5p,并可负调控 BC 细胞中其表达。此外,miR-1296-5p 可逆转 circ_0048764 对 BC 细胞活力、迁移、侵袭和凋亡的影响。此外,TRIM14 被证实是 miR-1296-5p 的下游靶标。Circ_0048764 通过靶向 miR-1296-5p 正向调节 BC 细胞中的 TRIM14 表达。总之,circ_0048764 通过调节 miR-1296-5p/TRIM14 轴促进了 BC 的发展。