Previous research manifested that miR-140-3p was a latent biomarker for osteoporosis. Nevertheless, the mechanism of miR-140-3p in osteoporosis is still not clear and needs ulteriorly studying. The purpose of our paper was to ulteriorly probe the underlying mechanism of miR-140-3p on osteoporosis. Firstly, based on the data acquired from GEO database, we found that miR-140-3p was highly expressed; meanwhile, MCF2L was lowly expressed in osteoporosis patients. Upregulation/downregulation of miR-140-3p by miR-140-3p mimic/inhibitor restrained/promoted MC3T3-E1 cell viability and differentiation. However, miR-140-3p over-expression/downregulation accelerated/repressed MC3T3-E1 cell apoptosis. MCF2L was forecasted as a target of miR-140-3p by miRanda, miRWalk, and TargetScan miRNA target gene prediction software. Luciferase reporter assay confirmed that MCF2L could be directly targeted by miR-140-3p. Moreover, we identified that the expression of MCF2L was negatively regulated by miR-140-3p. From rescue assays, we discovered that knockdown of MCF2L weakened the promoting influence of miR-140-3p ablation on MC3T3-E1 cell viability and differentiation, and receded the suppressing impact of miR-140-3p reduction on MC3T3-E1 cell apoptosis. Above all, this research disclosed that miR-140-3p repressed preosteoblast viability and differentiation while promoted preosteoblast apoptosis via targeting MCF2L. Our discoveries might afford a theoretical basis of developing a latent novel target for osteoporosis therapy.

中文翻译：

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通过下调骨质疏松症中的MCF2L，miR-140-3p对成骨细胞的存活和分化具有抑制作用。

先前的研究表明，miR-140-3p是骨质疏松症的潜在生物标记。然而，miR-140-3p在骨质疏松症中的机制仍不清楚，需要进一步研究。本文的目的是进一步探究miR-140-3p对骨质疏松症的潜在机制。首先，基于从GEO数据库获得的数据，我们发现miR-140-3p被高度表达。同时，MCF2L在骨质疏松症患者中低表达。miR-140-3p模拟物/抑制剂可抑制/促进MC3T3-E1细胞的活力和分化，从而上调/下调miR-140-3p。但是，miR-140-3p的过度表达/下调会加速/抑制MC3T3-E1细胞凋亡。miRanda，miRWalk和TargetScan miRNA目标基因预测软件将MCF2L预测为miR-140-3p的目标。萤光素酶报告基因检测证实miR-140-3p可以直接靶向MCF2L。此外，我们发现miR-140-3p负调控MCF2L的表达。从救援分析中，我们发现敲低MCF2L减弱了miR-140-3p消融对MC3T3-E1细胞存活和分化的促进作用，并消除了miR-140-3p减少对MC3T3-E1细胞凋亡的抑制作用。最重要的是，这项研究表明，miR-140-3p通过靶向MCF2L抑制成骨细胞的活力和分化，同时促进成骨细胞的凋亡。我们的发现可能为开发潜在的新型骨质疏松治疗靶标提供理论依据。从救援分析中，我们发现敲低MCF2L减弱了miR-140-3p消融对MC3T3-E1细胞存活和分化的促进作用，并消除了miR-140-3p减少对MC3T3-E1细胞凋亡的抑制作用。最重要的是，这项研究表明，miR-140-3p通过靶向MCF2L抑制成骨细胞的活力和分化，同时促进成骨细胞的凋亡。我们的发现可能为开发潜在的新型骨质疏松治疗靶标提供理论依据。从救援分析中，我们发现敲低MCF2L减弱了miR-140-3p消融对MC3T3-E1细胞存活和分化的促进作用，并消除了miR-140-3p减少对MC3T3-E1细胞凋亡的抑制作用。最重要的是，这项研究表明，miR-140-3p通过靶向MCF2L抑制成骨细胞的活力和分化，同时促进成骨细胞的凋亡。我们的发现可能为开发潜在的新型骨质疏松治疗靶标提供理论依据。这项研究表明，miR-140-3p通过靶向MCF2L抑制成骨细胞的活力和分化，同时促进成骨细胞的凋亡。我们的发现可能为开发潜在的新型骨质疏松治疗靶标提供理论依据。这项研究表明，miR-140-3p通过靶向MCF2L抑制成骨细胞的活力和分化，同时促进成骨细胞的凋亡。我们的发现可能为开发潜在的新型骨质疏松治疗靶标提供理论依据。