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miR-22 通过靶向 WRNIP1 增强小细胞肺癌的放射敏感性。

miR-22 enhances the radiosensitivity of small-cell lung cancer by targeting the WRNIP1.

机构信息

Department of Radiotherapy, Tianjin Medical University Second Hospital, Tianjin, China.

Department of Respiration, Tianjin Medical University Second Hospital, Tianjin, China.

出版信息

J Cell Biochem. 2019 Oct;120(10):17650-17661. doi: 10.1002/jcb.29032. Epub 2019 Jun 12.

Abstract

Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by high cellular proliferation and early distant metastasis. Our study aimed to explore the effect of miR-22-3p (miR-22, for short) on SCLC radiosensitivity and its molecular mechanisms. The expression level of miR-22 was evaluated in a human normal lung epithelial cell line and a human SCLC cell line, and cell apoptosis and migration were detected. The expression of the miR-22 direct target WRNIP1 mRNA and protein were explored. Five differentially expressed genes were detected. The miR-22 expression in NCI-H446 was significantly decreased, and miR-22 overexpression significantly promoted cell apoptosis. miR-22 overexpression could significantly inhibit the cell migration of SCLC cells, and miR-22 had a negative regulatory effect on WRNIP1 mRNA and protein levels. KLK8 was downregulated, and the messenger RNA (mRNA) of four other genes (PC, SCUBE1, STC1, and GPM6A) was upregulated mRNA in cells overexpressing miR-22, which was in accordance with the bioinformatics analysis. miR-22 could enhance the radiosensitivity of SCLC by targeting WRNIP1.

摘要

小细胞肺癌(SCLC)是一种具有高细胞增殖和早期远处转移特征的侵袭性恶性肿瘤。我们的研究旨在探讨 miR-22-3p(miR-22)对 SCLC 放射敏感性的影响及其分子机制。在人正常肺上皮细胞系和人 SCLC 细胞系中评估了 miR-22 的表达水平,并检测了细胞凋亡和迁移。探讨了 miR-22 直接靶基因 WRNIP1 mRNA 和蛋白的表达。检测到 5 个差异表达基因。NCI-H446 中 miR-22 的表达明显降低,miR-22 过表达显著促进细胞凋亡。miR-22 过表达可显著抑制 SCLC 细胞的迁移,对 WRNIP1 mRNA 和蛋白水平具有负调控作用。KLK8 下调,过表达 miR-22 的细胞中其他四个基因(PC、SCUBE1、STC1 和 GPM6A)的信使 RNA(mRNA)上调,与生物信息学分析一致。miR-22 可通过靶向 WRNIP1 增强 SCLC 的放射敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a389/6771739/260094bbe349/JCB-120-17650-g001.jpg

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