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Silencing long noncoding RNA colon cancer-associated transcript-1 upregulates microRNA-34a-5p to promote proliferation and differentiation of osteoblasts in osteoporosis
Cancer Gene Therapy ( IF 4.8 ) Pub Date : 2021-01-05 , DOI: 10.1038/s41417-020-00264-7
Fangke Hu 1 , Chengying Jiang 2 , Guoyun Bu 1 , Yiru Fu 2 , Yanfang Yu 3
Affiliation  

Long noncoding RNAs (lncRNAs) have been revealed to be related to multiple physiological and pathology processes such as development, carcinogenesis, and osteogenesis. It is reported that lncRNAs might exert function in osteoblast differentiation and bone formation. Here, we determined this study to clarify whether lncRNA CCAT1 could regulate osteoblast proliferation and differentiation in ovariectomized rats with osteoporosis. The osteoporosis models were established by bilateral ovariectomy and treated with CCAT1 siRNAs to discuss the effect of CCAT1 on pathological changes and osteocyte apoptosis in ovariectomized rats with osteoporosis. The osteoblasts from ovariectomized rats were cultured in vitro, which were then treated with CCAT1 siRNAs to explore the role of CCAT1 in osteoblast proliferation and differentiation. Moreover, the relationships among CCAT1, miR-34a-5p, and SMURF2 were confirmed. CCAT1 and SMURF2 were amplified while miR-34a-5p expression was inhibited in bone tissues and osteoblasts of ovariectomized rats with osteoporosis. Inhibited CCAT1 improved pathology and restricted osteocyte apoptosis of bone tissues in ovariectomized rats with osteoporosis in vivo, and also enhanced differentiation, mineralization abilities, and proliferation, and suppressed apoptosis of osteoblasts from ovariectomized rats in vitro through upregulating miR-34a-5p expression. LncRNA CCAT1 could competitively bind with miR-34a-5p to prevent the degradation of its target gene SMURF2. Results of this research suggested that the CCAT1 inhibits the proliferation and differentiation of osteoblasts in rats with osteoporosis by binding to miR-34a-5p, providing novel biomarkers for osteoporosis treatment.



中文翻译:

沉默长链非编码 RNA 结肠癌相关转录本 1 上调 microRNA-34a-5p 促进骨质疏松症中成骨细胞的增殖和分化

已发现长链非编码 RNA (lncRNA) 与发育、癌变和成骨等多种生理和病理过程有关。据报道,lncRNAs可能在成骨细胞分化和骨形成中发挥作用。在这里,我们确定了这项研究,以阐明 lncRNA CCAT1 是否可以调节去卵巢大鼠骨质疏松症的成骨细胞增殖和分化。采用双侧卵巢切除术建立骨质疏松模型,并用CCAT1 siRNAs处理,探讨CCAT1对去卵巢骨质疏松大鼠病理变化和骨细胞凋亡的影响。体外培养卵巢切除大鼠的成骨细胞,然后用CCAT1 siRNA处理,探索CCAT1在成骨细胞增殖和分化中的作用。而且,证实了 CCAT1、miR-34a-5p 和 SMURF2 之间的关系。在患有骨质疏松症的去卵巢大鼠的骨组织和成骨细胞中,CCAT1 和 SMURF2 被扩增,而 miR-34a-5p 的表达受到抑制。抑制 CCAT1 可改善骨质疏松去卵巢大鼠体内骨组织的病理学和骨细胞凋亡,并通过上调 miR-34a-5p 表达,增强体外去卵巢大鼠成骨细胞的分化、矿化能力和增殖,并抑制成骨细胞的凋亡。LncRNA CCAT1 可以与 miR-34a-5p 竞争性结合,以防止其靶基因 SMURF2 的降解。本研究结果表明,CCAT1 通过与 miR-34a-5p 结合,抑制骨质疏松大鼠成骨细胞的增殖和分化,

更新日期:2021-01-05
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