Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression
Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression
复制标题
Hsa_circ_0009361 作为 miR-582 的海绵，通过调节 APC2 表达抑制结直肠癌进展
DOI：
10.1042/cs20190286
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发表时间：
2019-05-31
期刊：
影响因子：
6
通讯作者：
Jiang, Jingting
中科院分区：
文献类型：
--
作者：
Geng, Yiting;Zheng, Xiao;Jiang, Jingting
环状RNA(CircRNA)在人类恶性肿瘤的发生发展中起着重要作用。近年来，在各种肿瘤中发现和研究了越来越多的CircRNAs。然而，CircRNAs在结直肠癌中的表达模式和生物学功能在很大程度上尚不清楚。在本研究中，hsA-CIRC 0009361在结直肠癌组织和细胞中显著下调。HsA CIRC 0009361低表达促进了结直肠癌细胞的增殖、上皮-间充质转化、迁移和侵袭。经荧光原位杂交、免疫沉淀法和荧光素酶报告基因鉴定，HSACIRC 0009361为miR-582的海绵。HSA CIRC 0009361过表达通过与miR-582竞争性结合，上调腺瘤性息肉病结肠2(APC2)的表达，并抑制Wnt/β-catenin通路的活性。外源性miR-582和APC2干预可逆转hsA-CIRC 0009361介导的多种生物学功能。体内实验也证实了hsa circ 0009361对结直肠癌的生长和转移有抑制作用。HSACIRC 0009361作为miR-582的抑瘤海绵，可上调APC2的表达，抑制Wnt/β-catenin信号转导，抑制结直肠癌的生长和转移。总的来说，hsa circ 0009361/miR-582/apc2网络可以作为结直肠癌患者的潜在治疗靶点。
Circular RNA (circRNA) plays an important role in the development of human malignant tumors. Recently, an increasing number of circRNAs have been identified and investigated in various tumors. However, the expression pattern and biological function of circRNAs in colorectal cancer (CRC) still remain largely unexplored. In the present study, hsa circ 0009361 was significantly down-regulated in CRC tissues and cells. Low expression level of hsa circ 0009361 promoted the proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion of CRC cells. Hsa circ 0009361 was identified as the sponge of miR-582 by fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and luciferase reporter assays. Overexpression of hsa circ 0009361 up-regulated the expression of adenomatous polyposis coli 2 (APC2) and inhibited the activity of the Wnt/beta-catenin pathway by competitively combining with miR-582. Exogenous miR-582 and APC2 interventions could reverse the multiple biological functions mediated by hsa circ 0009361 in CRC cells. In vivo experiments also confirmed that hsa circ 0009361 inhibited the growth and metastasis of CRC. Hsa circ 0009361 acted as a tumor suppressive sponge of miR-582, which could up-regulate the expression of APC2, inhibit the Wnt/beta-catenin signaling, and suppress the growth and metastasis of CRC. Collectively, the hsa circ 0009361/miR-582/APC2 network could be employed as a potential therapeutic target for CRC patients.