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环状RNA circMAN2B2通过miR-1275/FOXK1轴促进肺癌细胞增殖和侵袭。

Circular RNA circMAN2B2 facilitates lung cancer cell proliferation and invasion via miR-1275/FOXK1 axis.

作者信息

Ma Xuemei, Yang Xiaodong, Bao Wenhua, Li Shumin, Liang Shanshan, Sun Yunhui, Zhao Yunwei, Wang Jing, Zhao Chenxu

机构信息

Department of Respiratory Disease, First Affiliated Hospital of Jiamusi University, Jiamusi 154003, China.

Department of Respiratory Disease, First Affiliated Hospital of Jiamusi University, Jiamusi 154003, China.

出版信息

Biochem Biophys Res Commun. 2018 Apr 15;498(4):1009-1015. doi: 10.1016/j.bbrc.2018.03.105. Epub 2018 Mar 16.

Abstract

Lung cancer remains a leading cause of cancer-related deaths worldwide. In the past years, increasing reports indicate that circular RNAs (circRNAs) exert a great important role in human cancers, including lung cancer. However, the knowledge about circRNA in lung cancer remains very little so far. In the present study, we screened out a highly expressed novel circRNA named circMAN2B2 in lung cancer tissues. We investigated the function of circMAN2B2 and found that circMAN2B2 knockdown significantly inhibited cell proliferation and invasion in both H1299 and A549 lung cancer cells. Mechanistically, we found that circMAN2B2 could sponge miR-1275 to inhibit its level. Through a series of functional experiments, we dissected the role of miR-1275 in lung cancer and proved the anti-tumor role of miR-1275. Furthermore, we found that miR-1275 exerted its role in lung cancer by regulating FOXK1 expression. In addition, we demonstrated that restoration of FOXK1 could rescue circMAN2B2 knockdown-induced repression of cell proliferation and invasion. Taken together, our study demonstrated that circMAN2B2 acts as an oncogenic role in lung cancer through promoting FOXK1 expression by sponging miR-1275.

摘要

肺癌仍然是全球癌症相关死亡的主要原因。在过去几年中,越来越多的报道表明,环状RNA(circRNA)在包括肺癌在内的人类癌症中发挥着非常重要的作用。然而,到目前为止,关于肺癌中circRNA的了解仍然很少。在本研究中,我们在肺癌组织中筛选出一种高表达的新型circRNA,命名为circMAN2B2。我们研究了circMAN2B2的功能,发现敲低circMAN2B2可显著抑制H1299和A549肺癌细胞的增殖和侵袭。机制上,我们发现circMAN2B2可以吸附miR-1275以抑制其水平。通过一系列功能实验,我们剖析了miR-1275在肺癌中的作用,并证明了miR-1275的抗肿瘤作用。此外,我们发现miR-1275通过调节FOXK1的表达在肺癌中发挥作用。此外,我们证明恢复FOXK1可以挽救circMAN2B2敲低诱导的细胞增殖和侵袭抑制。综上所述,我们的研究表明,circMAN2B2通过吸附miR-1275促进FOXK1表达,在肺癌中发挥致癌作用。

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