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.
Our objective was to investigate the effect of circSMARCC1 on the developmental and biological behavior of colorectal cancer (CRC).
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.
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.
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.
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。
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。
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。
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。
