Hsa_circularRNA_0079201 suppresses chondrocyte proliferation and endochondral ossification by regulating the microRNA‑140‑3p/SMAD2 signaling pathway in idiopathic short stature.
Hsa_circularRNA_0079201 suppresses chondrocyte proliferation and endochondral ossification by regulating the microRNA‑140‑3p/SMAD2 signaling pathway in idiopathic short stature.
复制标题
Hsa_circularRNA_0079201 通过调节特发性矮身材中的 microRNA-140-3p/SMAD2 信号通路抑制软骨细胞增殖和软骨内骨化
DOI：
10.3892/ijmm.2020.4737
复制
发表时间：
2020-12
影响因子：
5.4
通讯作者：
Jia J
中科院分区：
文献类型：
--
作者：
Liu X;Yan C;Deng X;Jia J
环状（circ）RNA是一类重要的非编码RNA，参与不同的病理和生理功能，例如纵向骨生长。然而，circRNA 表达增加或减少对特发性身材矮小 (ISS) 的影响仍然很大程度上未知。本研究比较了 ISS 患者和健康个体的 circRNA 表达模式，以确定参与 ISS 发病机制调节的差异表达的 circRNA 及其靶标 microRNA (miR)。微阵列分析显示，ISS 患者中有 145 个 circRNA 存在差异表达，其中包括 83 个上调和 62 个下调的 circRNA。逆转录定量PCR证实，与正常个体相比，ISS患者的hsa_circRNA_0079201含量增加，而人软骨细胞中hsa_circRNA_0079201的过度表达显示出显着抑制其增殖、肥大和软骨内骨化能力。荧光素酶报告基因检测发现 circRNA_0079201 充当 miR-140-3p 海绵。原位杂交证实了 circRNA_0079201 和 miR-140-3p 在 C57 小鼠的人软骨细胞和新生股骨生长板中共定位，而救援实验表明 miR-140-3p 过表达逆转了 circRNA_0079201 过表达引起的人软骨细胞增殖、肥大和软骨内骨化的抑制。生物信息学分析和荧光素酶报告基因分析表明SMAD2是miR-140-3p的潜在靶基因。此外，在人软骨细胞中过表达 circRNA_0079201 可抑制 miR-140-3p 并增加 SMAD2 蛋白表达水平。综上所述，ISS 中的软骨细胞增殖、肥大和软骨内骨化受到由 hsa_circRNA_0079201/miR-140-3p/SMAD2 通路组成的新型调控轴的抑制。本研究提供的证据表明 hsa_circRNA_0079201 可能是 ISS 治疗的潜在靶点。
Circular (circ)RNAs are an important group of non-coding RNAs involved in different pathological and physiological functions, such as longitudinal bone growth. However, the effects of an increase or decrease in circRNA expression on idiopathic short stature (ISS) remain largely unknown. The present study compared the circRNA expression patterns of patients with ISS and healthy individuals to identify differentially expressed circRNAs involved in the regulation of ISS pathogenesis and their target microRNAs (miR). Microarray analysis revealed that 145 circRNAs were differentially expressed in patients with ISS, including 83 up- and 62 downregulated circRNAs. Reverse transcription-quantitative PCR confirmed that hsa_circRNA_0079201 was increased in patients with ISS compared with that in the normal individuals, whilst hsa_circRNA_0079201 overexpression in human chondrocytes was shown to significantly suppress their proliferation, hypertrophy and endochondral ossification abilities. Luciferase reporter assays identified that circRNA_0079201 acted as an miR-140-3p sponge. In situ hybridization confirmed the co-localization of circRNA_0079201 and miR-140-3p in the human chondrocyte and neonatal femur growth plate of C57 mice, while rescue experiments demonstrated that miR-140-3p overexpression reversed the inhibition of human chondrocyte proliferation, hypertrophy and endochondral ossification, caused by circRNA_0079201 overexpression. Bioinformatics analysis and luciferase reporter assays revealed that SMAD2 was a potential target gene of miR-140-3p. Furthermore, overexpressing circRNA_0079201 in human chondrocytes suppressed miR-140-3p and increased SMAD2 protein expression level. Taken together, chondrocyte proliferation, hypertrophy and endochondral ossification in ISS was suppressed by a novel regulatory axis consisting of the hsa_circRNA_0079201/miR-140-3p/SMAD2 pathway. The present study provided evidence that hsa_circRNA_0079201 may be a potential target for ISS therapy.
登录
查看更多内容
影响因子：
4.8
作者：
Jee, Youn Hee;Wang, Jinhee;Baron, Jeffrey
通讯作者：
Baron, Jeffrey
影响因子：
5
作者：
Greene J;Baird AM;Brady L;Lim M;Gray SG;McDermott R;Finn SP
通讯作者：
Finn SP
影响因子：
3.4
作者：
Heo, Sun Hee;Choi, Jin-Ho;Yoo, Han-Wook
通讯作者：
Yoo, Han-Wook
印度刺猬缺失对间充质细胞的影响：诱导中间软骨支架骨化导致生长板和指骨关节缺失、短肢和侏儒表型
影响因子：
4
作者：
Sun, Jian;Wei, Xiaochun;Wei, Lei
通讯作者：
Wei, Lei
IHH下调对软骨细胞生长和分化的抑制作用。
影响因子：
2.7
作者：
Deng A;Zhang H;Hu M;Liu S;Wang Y;Gao Q;Guo C
通讯作者：
Guo C