Medical College, Yanbian University, Yanji, 133002, China.
Tumor Biotherapy Center, Jilin Province People's Hospital, Changchun, China.
Eur J Med Res. 2022 Jul 16;27(1):121. doi: 10.1186/s40001-022-00750-8.
Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. P21 activated kinase 4 (PAK4) and Breast cancer anti-estrogen resistance 3 (BCAR3) have been reported to be involved in numerous aspects in tumorous progression. In this study, we propose to screen multi-targeted microRNAs. (miRNAs), which simultaneously inhibit neoplastic evolution through suppressing the transcription of target genes.
MTT and Colony formation assays measured cell's viability and proliferation. Scratch wound and Transwell assays detected the ability in migration and invasion for SW116 cells. The multi-targeted microRNAs of PAK4 and BCAR3 were predicted using bioinformatics analysis and verified by conducting dual luciferase reporter assay, western blot and qRT-PCR that could detect the expression levels of miR-199a/b-3p.
The knockdown of PAK4 significantly impeded proliferation and colony formation of SW1116 cells when the knockdown of BCAR3 hindered migration and invasion of SW1116 cells. MiR-199a/b-3p directly targeted the 3'-UTR of PAK4 and BCAR3, further effected proliferation, colony formation, migration, and invasion of SW1116 cells. PAK4 or BCAR3 overexpression could partially reversed inhibitory effects of miR-199a/b-3p.
These results provided a new multi-targeted cite for cancerous suppressant to improve the prognosis of CRC inpatients.
结直肠癌（CRC）是全球癌症相关死亡的主要原因之一。已报道 P21 激活激酶 4（PAK4）和乳腺癌雌激素抵抗 3（BCAR3）参与肿瘤进展的许多方面。在这项研究中，我们提出筛选多靶向 microRNAs（miRNAs），通过抑制靶基因的转录，同时抑制肿瘤的进化。
MTT 和集落形成测定法测量细胞活力和增殖。划痕实验和 Transwell 实验检测 SW116 细胞的迁移和侵袭能力。使用生物信息学分析预测 PAK4 和 BCAR3 的多靶向 microRNAs，并通过双荧光素酶报告基因测定、Western blot 和 qRT-PCR 验证 miR-199a/b-3p 的表达水平。
当敲低 BCAR3 抑制 SW1116 细胞的迁移和侵袭时，PAK4 的敲低显着抑制了 SW1116 细胞的增殖和集落形成。miR-199a/b-3p 直接靶向 PAK4 和 BCAR3 的 3'-UTR，进一步影响 SW1116 细胞的增殖、集落形成、迁移和侵袭。PAK4 或 BCAR3 的过表达可以部分逆转 miR-199a/b-3p 的抑制作用。
这些结果为癌症抑制剂提供了一个新的多靶向靶点，以改善 CRC 患者的预后。
