The First District of Oncology Department of Hainan People's Hospital, No. 19 Xiuhua Road, Xiuying District, Haikou, 570000, Hainan, China.
Biochem Cell Biol. 2021 Apr;99(2):241-248. doi: 10.1139/bcb-2020-0239. Epub 2020 Sep 21.
Many reports have indicated that long non-coding RNAs (lncRNAs) are closely associated with the occurrence and development of various cancers. Musculin antisense RNA 1 (MSC-AS1) is a an lncRNA known to act as an oncogene in several types of human cancers; however, its specific function in lung adenocarcinoma (LUAD) is still unclear. For this study, we designed and conducted experiments to clarify the function of the lncRNA MSC-AS1 in LUAD and its underlying mechanisms. We found that the expression of MSC-AS1 was significantly higher in LUAD tissues and cells than that in normal ones. Through loss-of function assays, we confirmed that the proliferation of LUAD cells was significantly restrained by down-regulation of MSC-AS1 and the rate of cell apoptosis was accelerated. The results from our mechanistic experiments showed that MSC-AS1 interacts with microRNA-33b-5p (miR-33b-5p). Moreover, glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) was found to be a direct target gene of miR-33b-5p, and it has similar functions to MSC-AS1. Further, inhibition of miR-33b-5p or overexpression GPAM reversed the inhibitory effects of MSC-AS1 silencing on LUAD cell growth. In short, MSC-AS1 facilitates LUAD progression through sponging miR-33b-5p to up-regulate GPAM.
许多报告表明,长非编码 RNA(lncRNA)与各种癌症的发生和发展密切相关。肌球蛋白反义 RNA 1(MSC-AS1)是一种在几种人类癌症中被认为是癌基因的 lncRNA;然而,其在肺腺癌(LUAD)中的具体功能仍不清楚。在这项研究中,我们设计并进行了实验,以阐明 lncRNA MSC-AS1 在 LUAD 中的功能及其潜在机制。我们发现,MSC-AS1 在 LUAD 组织和细胞中的表达明显高于正常组织和细胞。通过功能丧失实验,我们证实下调 MSC-AS1 显著抑制 LUAD 细胞的增殖,加速细胞凋亡。我们的机制实验结果表明,MSC-AS1 与 microRNA-33b-5p(miR-33b-5p)相互作用。此外,甘油-3-磷酸酰基转移酶,线粒体(GPAM)被发现是 miR-33b-5p 的直接靶基因,并且具有与 MSC-AS1 相似的功能。进一步,抑制 miR-33b-5p 或过表达 GPAM 逆转了 MSC-AS1 沉默对 LUAD 细胞生长的抑制作用。总之,MSC-AS1 通过海绵 miR-33b-5p 来上调 GPAM 促进 LUAD 进展。