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MAPKAPK5-AS1/miR-515-5p/CAB39 轴促进非小细胞肺癌细胞的增殖和迁移。

MAPKAPK5-AS1/miR-515-5p/CAB39 Axis Contributes to Non-small Cell Lung Cancer Cell Proliferation and Migration.

机构信息

Department of Respiratory, Nanjing First Hospital, Qinhuai District, No.68, Changle Road, Nanjing, 210012, Jiangsu, China.

出版信息

Mol Biotechnol. 2023 Nov;65(11):1887-1897. doi: 10.1007/s12033-023-00654-w. Epub 2023 Mar 3.

Abstract

Several studies have elucidated the pivotal function that long noncoding RNAs (lncRNAs) exerted on the initiation and development of various human carcinomas, encompassing non-small cell lung cancer (NSCLC). In spite of the fact that lncRNA MAPKAPK5 antisense RNA 1 (MAPKAPK5-AS1) has already been investigated by researchers and confirmed to play oncogenic roles in colorectal cancer, the underlying regulatory function of MAPKAPK5-AS1 in NSCLC cells still remain unclear. In our research, we found that MAPKAPK5-AS1 was expressed at high levels in NSCLC cells. Biological functional assays unclosed that downregulation of MAPKAPK5-AS1 repressed proliferative and migratory capacities whereas promoted apoptotic level in NSCLC cells. Molecular mechanism experiments confirmed that, in NSCLC cells, MAPKAPK5-AS1 combined with miR-515-5p and negatively modulated miR-515-5p expression level. Besides, calcium-binding protein 39 (CAB39) expression level was verified to be negatively modulated by miR-515-5p whereas positively modulated by MAPKAPK5-AS1 in NSCLC cells. Furthermore, rescued-function assays disclosed that inhibited miR-515-5p expression or overexpressed CAB39 could restore the suppressive influence of MAPKAPK5-AS1 silence on NSCLC progression. In summary, MAPKAPK5-AS1 upregulates CAB39 expression level to facilitate NSCLC progression by sequestering miR-515-5p, providing promising biomarkers for NSCLC treatment.

摘要

多项研究阐明了长非编码 RNA(lncRNA)在包括非小细胞肺癌(NSCLC)在内的多种人类癌中的启动和发展中发挥的关键作用。尽管研究人员已经研究了 lncRNA MAPKAPK5 反义 RNA 1(MAPKAPK5-AS1),并证实其在结直肠癌中发挥致癌作用,但 MAPKAPK5-AS1 在 NSCLC 细胞中的潜在调节功能仍不清楚。在我们的研究中,我们发现 MAPKAPK5-AS1 在 NSCLC 细胞中表达水平较高。生物学功能测定表明,下调 MAPKAPK5-AS1 抑制 NSCLC 细胞的增殖和迁移能力,而促进凋亡水平。分子机制实验证实,在 NSCLC 细胞中,MAPKAPK5-AS1 与 miR-515-5p 结合,并负调控 miR-515-5p 的表达水平。此外,钙结合蛋白 39(CAB39)的表达水平被证实被 miR-515-5p 负调控,而被 MAPKAPK5-AS1 在 NSCLC 细胞中正调控。此外,恢复功能测定表明,抑制 miR-515-5p 的表达或过表达 CAB39 可以恢复 MAPKAPK5-AS1 沉默对 NSCLC 进展的抑制作用。总之,MAPKAPK5-AS1 通过结合 miR-515-5p 上调 CAB39 的表达水平,促进 NSCLC 的进展,为 NSCLC 的治疗提供了有前途的生物标志物。

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