Department of Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China.
Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Eur J Pharmacol. 2017 Jul 15;807:168-173. doi: 10.1016/j.ejphar.2017.04.023. Epub 2017 Apr 20.
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although the development of therapy approaches, the outcome of CRC patients still is poor, understanding the biological mechanism of CRC progression is critical to improve the treatment strategies. miRNAs regulate CRC progression, we found miR-938 was upregulated in CRC tissues and cells, MTT assay, colony formation assay and soft agar growth assay suggested miR-938 overexpression promoted CRC cell proliferation, miR-938 knockdown inhibited CRC cell proliferation. Tumor suppressor PH domain Leucine-rich-repeats Protein Phosphatase 2 (PHLPP2) was a target of miR-938, miR-938 inhibited PHLPP2, luciferase activity assay suggested miR-938 directly bound to the 3'UTR of PHLPP2, meanwhile, we found miR-938 promoted c-Myc and Cyclin D1 expression, confirming miR-938 promoted CRC cell proliferation. Double knockdown of miR-938 and PHLPP2 promoted CRC cell proliferation, suggesting miR-938 promoted CRC cell proliferation by inhibiting PHLPP2.
结直肠癌(CRC)是全球癌症相关死亡的主要原因之一。尽管治疗方法不断发展,但 CRC 患者的预后仍然不佳,因此了解 CRC 进展的生物学机制对于改善治疗策略至关重要。miRNAs 调节 CRC 的进展,我们发现 miR-938 在 CRC 组织和细胞中上调,MTT assay、集落形成 assay 和软琼脂生长 assay 表明 miR-938 过表达促进 CRC 细胞增殖,miR-938 敲低抑制 CRC 细胞增殖。肿瘤抑制因子 PH 结构域富含亮氨酸重复蛋白磷酸酶 2(PHLPP2)是 miR-938 的靶标,miR-938 抑制 PHLPP2,荧光素酶活性 assay 表明 miR-938 直接结合 PHLPP2 的 3'UTR,同时,我们发现 miR-938 促进 c-Myc 和 Cyclin D1 的表达,证实 miR-938 促进 CRC 细胞增殖。miR-938 和 PHLPP2 的双重敲低促进 CRC 细胞增殖,表明 miR-938 通过抑制 PHLPP2 促进 CRC 细胞增殖。