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微小RNA-378通过下调Kruppel样因子9的表达促进骨肉瘤细胞增殖。

MiR-378 promotes the cell proliferation of osteosarcoma through down-regulating the expression of Kruppel-like factor 9.

作者信息

Peng Ningning, Miao Zhigang, Wang Liguo, Liu Binbin, Wang Guijiang, Guo Xu

机构信息

Department of Orthopedics, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, 061000, Hebei, China.

出版信息

Biochem Cell Biol. 2018 Oct;96(5):515-521. doi: 10.1139/bcb-2017-0186. Epub 2018 Feb 28.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in a variety of biological processes. Dysregulation of miRNAs is tightly associated with the malignancy of cancers. Aberrant expression of miR-378 has been observed in human cancers; however, the function of miR-378 in osteosarcoma (OS) remains largely unknown. Here, we showed that miR-378 was highly expressed in human OS tissues and cell lines. Overexpression of miR-378 significantly promoted the cell proliferation of OS cells. Molecular studies identified Kruppel-like factor-9 (KLF9) as a functional downstream target of miR-378. MiR-378 directly bound to the mRNA 3'-UTR region of KLF9 and suppressed the expression of KLF9. Highly expressed KLF9 reversed the promoting effect of miR-378 on the proliferation of OS cells. The expression level of miR-378 was negatively correlated with that of KLF9 in OS tissues. Collectively, our results demonstrated the molecular interaction between miR-378 and KLF9, indicating the therapeutic potential of miR-378 for OS.

摘要

微小RNA(miRNA)是一类小的非编码RNA,在多种生物学过程中发挥重要作用。miRNA的失调与癌症的恶性程度密切相关。在人类癌症中已观察到miR-378的异常表达;然而,miR-378在骨肉瘤(OS)中的功能仍 largely 未知。在此,我们表明miR-378在人类OS组织和细胞系中高表达。miR-378的过表达显著促进了OS细胞的增殖。分子研究确定Kruppel样因子9(KLF9)是miR-378的功能性下游靶标。miR-378直接结合到KLF9的mRNA 3'-UTR区域并抑制KLF9的表达。高表达的KLF9逆转了miR-378对OS细胞增殖的促进作用。在OS组织中,miR-378的表达水平与KLF9的表达水平呈负相关。总体而言,我们的结果证明了miR-378与KLF9之间的分子相互作用,表明miR-378对OS具有治疗潜力。

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