CircRNA SMARCC1 Sponges MiR-140-3p to Regulate Cell Progression in Colorectal Cancer
CircRNA SMARCC1 Sponges MiR-140-3p to Regulate Cell Progression in Colorectal Cancer
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DOI：
10.2147/cmar.s254185
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Qiu, Xiao-ming
中科院分区：
文献类型：
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作者：
Chen, Miao-sheng;Lin, Cui-hong;Qiu, Xiao-ming
目的：我们的目的是研究circSMARCC1对结直肠癌（CRC）发育和生物学行为的影响。材料和方法：采用qRT-PCR检测CRC组织和细胞系（SW620、HCT116、HT29和SW480）以及正常细胞系（NCM460）中circSAMRCC1和miR-140-3p的表达。检测circSMARCC1及其线性亚型的表达水平。进行荧光原位杂交以评估 circSAMRCC1 和 miR-140-3p 在 SW620 细胞系中的定位。分别使用 CCK8 和集落形成测定研究 circSAMRCC1 和 miR-140-3p 对细胞增殖的影响。使用 Transwell 实验测定 circSAMRCC1 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基因分析进一步评估circSMARCC1和miR-140-3p之间的结合关系。结果：CRC组织和四种细胞系中circSMARCC1的表达显着增加，并且circSMARCC1和miR-140-3p与组织中的表达水平呈负相关。 circSMARCC1 的下调降低了 CRC 细胞活力并抑制体外转移和抑制蛋白质（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，miR-140-3p抑制剂逆转了circSMARCC1下调对CRC细胞增殖、迁移和侵袭的影响。结论：circSMARCC1与miR-140-3p竞争性结合，并通过circSMARCC1/miR-140-3p/MMPs发挥作用 轴作为结直肠癌致癌物，证明了其作为结直肠癌治疗生物标志物的潜力。
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.