Department of Gastrointestinal Surgery, Tangshan Central Hospital, Tangshan Youyi Road and Changning Road interchange westbound 300 meters, Tangshan, 063000, China.
Department of Anus and Intestine Surgery, Tangshan Central Hospital, Tangshan Youyi Road and Changning Road interchange westbound 300 meters, Tangshan, 063000, China.
Mol Biotechnol. 2022 Dec;64(12):1388-1400. doi: 10.1007/s12033-022-00515-y. Epub 2022 Jun 13.
Accumulating studies have demonstrated that CADM2 modulated malignant phenotype of various cancer cells, while its regulatory function and mechanism have not yet been reported. In this study, qRT-PCR was utilized to measure CADM2 mRNA level in normal cells and colon cancer cells, also, IHC and WB were applied to detect CADM2 protein expression in colon tissues, exhibiting low mRNA and protein levels of CADM2 in colon cancer. Applying cell function experiments, the impacts of CADM2 on colon cell phenotypes were examined, and the results illustrated that upregulating CADM2 remarkably repressed proliferation, invasion, migration, cell cycle of colon cancer cells, and facilitated cell apoptosis. Thus, it could be considered that CADM2 served as a tumor repressor gene in colon cancer. Moreover, the outcomes of dual-luciferase assay displayed that miR-17-5p could target CADM2, and overexpressing miR-17-5p could notably inhibit the mRNA and protein expression levels of CADM2. We, therefore, assumed that CADM2 was a downstream target of miR-139-5p. qRT-PCR was conducted to assess miR-17-5p level in colon cancer cells and normal cells, verifying a high miR-17-5p expression in the cancer cells. The effects of miR-17-5p on colon cell phenotypes were examined as well, where we determined that miR-17-5p served as a tumor-promoting factor. Finally, the rescue experiments exhibited that miR-17-5p could activate tumor-promoting phenotypes, while such activating effects could be reversed by upregulating CADM2. In short, the study proved that miR-17-5p facilitated malignant progression of colon cancer through targeting CADM2 at a post-transcriptional level. Our findings offer new insight into molecular therapy of colon cancer patients.
越来越多的研究表明 CADM2 调节了各种癌细胞的恶性表型，但其调节功能和机制尚未报道。在本研究中，我们利用 qRT-PCR 测量了正常细胞和结肠癌细胞中的 CADM2 mRNA 水平，同时应用 IHC 和 WB 检测了结肠组织中 CADM2 蛋白的表达，结果显示 CADM2 在结肠癌中的 mRNA 和蛋白水平较低。通过细胞功能实验，研究了 CADM2 对结肠细胞表型的影响，结果表明上调 CADM2 可显著抑制结肠癌细胞的增殖、侵袭、迁移和细胞周期，并促进细胞凋亡。因此，可以认为 CADM2 在结肠癌中作为一种肿瘤抑制基因发挥作用。此外，双荧光素酶报告基因实验结果表明，miR-17-5p 可以靶向 CADM2，过表达 miR-17-5p 可以显著抑制 CADM2 的 mRNA 和蛋白表达水平。因此，我们假设 CADM2 是 miR-139-5p 的下游靶基因。我们通过 qRT-PCR 检测了结肠癌细胞和正常细胞中的 miR-17-5p 水平，证实了癌症细胞中 miR-17-5p 的高表达。我们还研究了 miR-17-5p 对结肠细胞表型的影响，确定了 miR-17-5p 作为一种肿瘤促进因子的作用。最后，通过挽救实验表明，miR-17-5p 可以通过在转录后水平靶向 CADM2 激活肿瘤促进表型，而这种激活作用可以通过上调 CADM2 来逆转。总之，本研究证明 miR-17-5p 通过在转录后水平靶向 CADM2 促进了结肠癌的恶性进展。我们的研究结果为结肠癌患者的分子治疗提供了新的见解。
