Department of Gynecology, Zibo Maternal and Child Health Hospital, Zibo 255000, Shandong, China.
Department of Gynecology and Obstetrics, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101101, China.
Biomed Res Int. 2020 Jan 3;2020:4351671. doi: 10.1155/2020/4351671. eCollection 2020.
Cervical cancer is one of the malignant tumors that seriously threaten women's health. The mechanism of development needs to be deeply studied. In recent years, lncRNA has been identified as one of the important factors affecting the malignant progression of tumors. In this study, we illustrated the important mechanism of lncRNA CAR10 in the development of cervical cancer. We found that CAR10 is significantly increased in4 cervical cancer tissues and cells, which can promote the proliferation of cervical cancer cells in vitro and in vivo, indicating that CAR10 is involved in the progression of cervical cancer as an oncogene. Further studies showed that CAR10 is a target gene of miR-125b-5p, and miR-125b-5p can inhibit the effect of CAR10 on the proliferation of cervical cancer cells. In addition, we also found that 3-phosphoinositide-dependent protein kinase 1 (PDPK1) is also a target gene of miR-125b-5p, and CAR10 can upregulate the expression level of PDPK1. The results showed that CAR10 acts as a ceRNA to upregulate the expression of PDPK1 by sponging miR-125b-5p. Knockdown of PDPK1 can inhibit the effect of CAR10 on cervical cancer cells. Our study demonstrates that, based on ceRNA mechanism, CAR10/miR-125b-5p/PDPK1 network can regulate the proliferation of cervical cancer cells and play an important role in the development of cervical cancer. In addition, our study also suggests that intervention of CAR10/miR-125b-5p/PDPK1 network may be a new strategy for targeted therapy of cervical cancer.
宫颈癌是严重威胁女性健康的恶性肿瘤之一，其发生发展的机制有待深入研究。近年来，lncRNA 被鉴定为影响肿瘤恶性进展的重要因素之一。在本研究中，我们阐述了 lncRNA CAR10 在宫颈癌发生发展中的重要机制。我们发现 CAR10 在 4 种宫颈癌组织和细胞中显著上调，能够促进宫颈癌细胞在体外和体内的增殖，表明 CAR10 作为癌基因参与宫颈癌的进展。进一步研究表明，CAR10 是 miR-125b-5p 的靶基因，miR-125b-5p 可以抑制 CAR10 对宫颈癌细胞增殖的作用。此外，我们还发现 3-磷酸肌醇依赖性蛋白激酶 1（PDPK1）也是 miR-125b-5p 的靶基因，CAR10 可以上调 PDPK1 的表达水平。结果表明，CAR10 通过海绵吸附 miR-125b-5p 作为 ceRNA 上调 PDPK1 的表达。下调 PDPK1 可以抑制 CAR10 对宫颈癌细胞的作用。我们的研究表明，基于 ceRNA 机制，CAR10/miR-125b-5p/PDPK1 网络可以调节宫颈癌细胞的增殖，在宫颈癌的发生发展中发挥重要作用。此外，我们的研究还提示，干预 CAR10/miR-125b-5p/PDPK1 网络可能是宫颈癌靶向治疗的新策略。
