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环状 RNA FAM120B 敲低通过 miR-1205/PTBP1 轴抑制骨肉瘤发生。

CircFAM120B knockdown inhibits osteosarcoma tumorigenesis via the miR-1205/PTBP1 axis.

机构信息

Department of Traumatology, The First Affiliated Hospital, And College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan, China.

Department of Ophthalmology, XiPing County People's Hospital, Zhumadian 463900, Henan, China.

出版信息

Aging (Albany NY). 2021 Oct 29;13(20):23831-23841. doi: 10.18632/aging.203657.

Abstract

BACKGROUND

Osteosarcoma (OS) is a highly prevalent bone malignancy with poor clinical outcomes. Expression of the circular RNA, hsa_circ_0078767 (circFAM120B) is elevated in OS, however, its mechanisms in OS are unclear.

METHODS

CircFAM120B levels were detected in OS tissue and cell lines. Silenced circFAM120B experiments were performed to assess its effects on OS cancer phenotypes and tumor growth. Then, bioinformatics analyses were used to predict circFAM120B target microRNAs (miRNAs) and associated genes.

RESULTS

CircFAM120B and the transcription factor, PTBP1 were elevated in OS tissue and cell lines, while miR-1205 was poorly expressed. Silenced circFAM120B significantly suppressed OS cell proliferation and invasion, and inhibited tumor growth. CircFAM120B also appeared to function as an miR-1205 sponge, as miR-1205 bound to PTBP1. Interestingly, overexpressed PTBP1 (or miR-1205 inhibition) reversed the inhibitory effects mediated by circFAM120B downregulation in OS cells.

CONCLUSION

We hypothesize circFAM120B functions as a miR-1205 sponge to elevate PTBP1 levels, enhancing OS progression and associated malignant phenotypes. Thus, circFAM120B may function as a crucial mediator during OS progression.

摘要

背景

骨肉瘤(OS)是一种高发的骨恶性肿瘤,临床预后较差。环状 RNA hsa_circ_0078767(circFAM120B)在骨肉瘤中的表达升高,但其在骨肉瘤中的机制尚不清楚。

方法

检测骨肉瘤组织和细胞系中 circFAM120B 的水平。沉默 circFAM120B 实验用于评估其对骨肉瘤肿瘤表型和肿瘤生长的影响。然后,进行生物信息学分析以预测 circFAM120B 的靶微小 RNA(miRNA)和相关基因。

结果

circFAM120B 和转录因子 PTBP1 在骨肉瘤组织和细胞系中升高,而 miR-1205 表达水平较低。沉默 circFAM120B 显著抑制骨肉瘤细胞的增殖和侵袭,并抑制肿瘤生长。circFAM120B 似乎还作为 miR-1205 的海绵体发挥作用,因为 miR-1205 与 PTBP1 结合。有趣的是,过表达 PTBP1(或 miR-1205 抑制)逆转了 circFAM120B 下调在骨肉瘤细胞中介导的抑制作用。

结论

我们假设 circFAM120B 作为 miR-1205 的海绵体发挥作用,从而提高 PTBP1 水平,增强骨肉瘤的进展和相关恶性表型。因此,circFAM120B 可能在骨肉瘤进展过程中发挥重要的介导作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9a/8580345/86573afdb7ba/aging-13-203657-g001.jpg

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