Chen Wei, Li Qi, Du Jingjie, Li Xiaodi, Jiang Songshan, He Yuanli
Department of Gynecology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China.
Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510260, P.R. China.
Oncol Lett. 2018 Sep;16(3):4027-4032. doi: 10.3892/ol.2018.9096. Epub 2018 Jul 6.
MicroRNA-137 (miR-137) has been reported to be abnormally expressed in a variety of types of cancer, including ovarian cancer. However, the roles served by miR-137 in cancer are not fully understood. In the present study, 3 single guide RNAs (sgRNAs) were designed, synthesized and inserted into pXPR001 plasmids. The pXPR001-sgRNA plasmids were verified using sequencing and integrated into the genome of the ovarian cancer cell line, A2780, through lentiviral transduction, puromycin selection and single-cell culture. PCR products amplified from single-cell cultures using primers covering miR-137 targeting sites were sequenced to identify clones with miR-137 gene disruption. Genome editing was detected in 72% of the clones derived from sgRNA2, 4% from sgRNA3 and 0% from sgRNA1. Of the clones from sgRNA2, 32% contained 1 edited miR-137 allele and 40% contained 2 edited miR-137 alleles. The expression of miR-137 in clones #2 and #3 could not be detected by reverse transcription-quantitative polymerase chain reaction. In addition, an MTT assay demonstrated that clones #2 and #3 exhibited enhanced proliferation. In conclusion, an miR-137-knockout cell model was successfully established in A2780 cells using CRISPR/Cas9 technology.
据报道,微小RNA-137(miR-137)在包括卵巢癌在内的多种癌症类型中表达异常。然而,miR-137在癌症中的作用尚未完全明确。在本研究中,设计、合成了3条单向导RNA(sgRNA),并将其插入pXPR001质粒中。通过测序对pXPR001-sgRNA质粒进行验证,并通过慢病毒转导、嘌呤霉素筛选和单细胞培养将其整合到卵巢癌细胞系A2780的基因组中。使用覆盖miR-137靶向位点的引物对单细胞培养物扩增的PCR产物进行测序,以鉴定miR-137基因破坏的克隆。在源自sgRNA2的克隆中,72%检测到基因组编辑,源自sgRNA3的为4%,源自sgRNA1的为0%。在源自sgRNA2的克隆中,32%含有1个编辑的miR-137等位基因,40%含有2个编辑的miR-137等位基因。逆转录-定量聚合酶链反应无法检测到克隆#2和#3中miR-137的表达。此外,MTT试验表明克隆#2和#3的增殖增强。总之,利用CRISPR/Cas9技术在A2780细胞中成功建立了miR-137敲除细胞模型。