Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Cell Cycle. 2019 Dec;18(23):3325-3336. doi: 10.1080/15384101.2019.1676087. Epub 2019 Oct 10.
Osteosarcoma (OS) accounts for 9 percent of cancer-related deaths in young people. The PI3K/Akt signaling, a well-known carcinogenic signaling pathway in human cancer, cooperates with other signaling pathways such as Wnt signaling to promote cancer progression. Wnt7b, as a transforming member of the Wnt family, could activate mTORC1 through PI3K-AKT signaling and is upregulated in OS. In the present study, we found that miR-342-5p inhibits Wnt7b expression via direct binding to Wnt7b 3'-UTR. miR-342-5p overexpression remarkably suppressed the viability and invasion while enhanced the apoptosis of OS cells; meanwhile, Wnt7b, β-catenin, c-myc, and cyclin D1 proteins were reduced while E-cadherin protein showed to be increased. Consistent with its expression pattern, Wnt7b exerted oncogenic effects on OS cells. Wnt7b could significantly attenuate the impacts of miR-342-5p. In conclusion, we demonstrated a miR-342-5p/Wnt7b axis that regulates the capacity of OS cells to proliferate and to invade through Wnt/β-catenin signaling. The miR-342-5p/Wnt7b axis might be novel targets for OS targeted therapy, which needs further in vivo and clinical investigations.
骨肉瘤(OS)占年轻人癌症相关死亡的 9%。PI3K/Akt 信号通路是人类癌症中一种著名的致癌信号通路,与 Wnt 信号通路等其他信号通路合作,促进癌症进展。Wnt7b 作为 Wnt 家族的转化成员,可通过 PI3K-AKT 信号通路激活 mTORC1,并在 OS 中上调。在本研究中,我们发现 miR-342-5p 通过直接结合 Wnt7b 3'-UTR 抑制 Wnt7b 的表达。miR-342-5p 的过表达显著抑制 OS 细胞的活力和侵袭,同时增强细胞凋亡;同时,Wnt7b、β-catenin、c-myc 和 cyclin D1 蛋白减少,而 E-cadherin 蛋白增加。与表达模式一致,Wnt7b 对 OS 细胞发挥致癌作用。Wnt7b 可显著减弱 miR-342-5p 的影响。总之,我们证明了 miR-342-5p/Wnt7b 轴通过 Wnt/β-catenin 信号通路调节 OS 细胞增殖和侵袭的能力。miR-342-5p/Wnt7b 轴可能是 OS 靶向治疗的新靶点,需要进一步的体内和临床研究。