Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Sci Rep. 2023 Aug 22;13(1):13710. doi: 10.1038/s41598-023-40666-9.
RNA-binding protein Musashi1 (MSI1) shows an increased expression level in several cancers and has been introduced as a prognostic marker in some malignancies. It is expected that if any miRNA is encoded by this gene, it might have a role in cancer development or could be considered as a prognostic biomarker. Accordingly, in this study, we aimed to find novel miRNA(s) inside the intronic regions of the MSI1 gene. Here, we report two novel miRNAs within intron 4 of MSI1 gene, named MSM2 and MSM3, which were selected among several miRNA precursors predicted by bioinformatic studies. For experimental analysis, corresponding precursor miRNAs were transfected into HEK293T cells and exogenous expression of the mature miRNAs were detected. Two mature miRNAs, MSM3-3p and MSM3-5p were generated by MSM3 precursor and one, MSM2-5p was derived from MSM2. Besides, endogenous expression of MSM2-5p and MSM3-3p was detected in MCF-7 and SH-SY5Y cell lines. Expression of both mature miRNAs was also detected in clinical samples of breast cancer. Additionally, the interaction between the MSM3-3p and 3'UTR region of PDE11A was confirmed by dual luciferase assay. Overall, our data demonstrated that MSI1 gene encodes two novel miRNAs in breast cancer cells.
RNA 结合蛋白 Musashi1(MSI1)在几种癌症中表达水平升高,并已被引入一些恶性肿瘤的预后标志物。如果该基因编码任何 miRNA,它可能在癌症发展中起作用,或者可以被认为是一种预后生物标志物。因此,在这项研究中,我们旨在发现 MSI1 基因内含子区域内的新型 miRNA。在这里,我们报告了 MSI1 基因第 4 内含子中的两个新型 miRNA,分别命名为 MSM2 和 MSM3,它们是通过生物信息学研究预测的几种 miRNA 前体中选择的。为了进行实验分析,将相应的前体 miRNA 转染到 HEK293T 细胞中,并检测外源性成熟 miRNA 的表达。MSM3 前体产生了两个成熟 miRNA,MSM3-3p 和 MSM3-5p,而 MSM2 则来源于 MSM2。此外,在 MCF-7 和 SH-SY5Y 细胞系中检测到内源性 MSM2-5p 和 MSM3-3p 的表达。在乳腺癌的临床样本中也检测到了这两种成熟 miRNA 的表达。此外,通过双荧光素酶报告基因实验证实了 MSM3-3p 与 PDE11A 3'UTR 区域的相互作用。总之,我们的数据表明,MSI1 基因在乳腺癌细胞中编码两种新型 miRNA。