Chen Miao-Sheng, Lin Cui-Hong, Huang Ling-Yan, Qiu Xiao-Ming
Department of Pathology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, People's Republic of China.
Cancer Manag Res. 2020 Jun 23;12:4899-4910. doi: 10.2147/CMAR.S254185. eCollection 2020.
PURPOSE: Our objective was to investigate the effect of circSMARCC1 on the developmental and biological behavior of colorectal cancer (CRC). MATERIALS AND METHODS: The expression of circSAMRCC1 and miR-140-3p in CRC tissues and cell lines (SW620, HCT116, HT29 and SW480) and a normal cell line (NCM460) was detected using qRT-PCR. The expression levels of circSMARCC1 and its linear subtype were detected. Fluorescence in situ hybridization was performed for the evaluation of the localization of circSAMRCC1 and miR-140-3p in the SW620 cell line. The effects of circSAMRCC1 and miR-140-3p on cell proliferation were investigated using CCK8 and colony formation assays, respectively. The effects of circSAMRCC1 and miR-140-3p on cell migration and invasion were determined using Transwell assay. The binding relationship between circSMARCC1 and miR-140-3p was further assessed by bioinformatics, ChIRP analysis and double luciferase reporter assay. RESULTS: The expression of circSAMRCC1 in the CRC tissues and four cell lines is significantly increased, and circSMARCC1 and miR-140-3p are negatively correlated with expression level in the tissue. The downregulation of circSMARCC1 decreased CRC cell viability and suppressed metastasis in vitro and Inhibition of protein (MMP-2, MMP-9, VEGF) expression. miR-140-3p is downregulated in CRC tissues; miR-140-3p mimics inhibited SW620 cell viability, migration and invasion, and miR-140-3p inhibitors reversed the the effect of circSMARCC1 downregulation on cell proliferation, migration and invasion in CRC cells. CONCLUSION: circSMARCC1 competitively combined with miR-140-3p and functioned through a circSMARCC1/miR-140-3p/MMPs axis as a CRC carcinogen, demonstrating its potential as a biomarker for CRC treatment.
目的:我们的目标是研究环状SMARCC1对结直肠癌(CRC)发育和生物学行为的影响。 材料与方法:采用qRT-PCR检测环状SAMRCC1和miR-140-3p在CRC组织、细胞系(SW620、HCT116、HT29和SW480)以及正常细胞系(NCM460)中的表达。检测环状SMARCC1及其线性亚型的表达水平。进行荧光原位杂交以评估环状SAMRCC1和miR-140-3p在SW620细胞系中的定位。分别使用CCK8和集落形成试验研究环状SAMRCC1和miR-140-3p对细胞增殖的影响。使用Transwell试验确定环状SAMRCC1和miR-140-3p对细胞迁移和侵袭的影响。通过生物信息学、ChIRP分析和双荧光素酶报告试验进一步评估环状SMARCC1与miR-140-3p之间的结合关系。 结果:环状SMARCC1在CRC组织和四种细胞系中的表达显著增加,且环状SMARCC1和miR-140-3p与组织中的表达水平呈负相关。环状SMARCC1的下调降低了CRC细胞活力,并在体外抑制转移以及抑制蛋白(MMP-2、MMP-9、VEGF)表达。miR-140-3p在CRC组织中下调;miR-140-3p模拟物抑制SW620细胞活力、迁移和侵袭,且miR-140-3p抑制剂逆转了环状SMARCC1下调对CRC细胞增殖、迁移和侵袭的影响。 结论:环状SMARCC1与miR-140-3p竞争性结合,并作为一种CRC致癌物通过环状SMARCC1/miR-140-3p/MMPs轴发挥作用,证明了其作为CRC治疗生物标志物的潜力。
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