环状 RNA_0000392 通过 miR-193a-5p/PIK3R3/AKT 轴促进结直肠癌进展。
CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis.
机构信息
Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Department of General Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
出版信息
J Exp Clin Cancer Res. 2020 Dec 14;39(1):283. doi: 10.1186/s13046-020-01799-1.
BACKGROUND
Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer.
METHODS
The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms.
RESULTS
CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells.
CONCLUSIONS
CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.
背景
环状 RNA（circRNAs）作为非编码 RNA 家族的重要成员，其在疾病发病机制中的作用，尤其是在癌症的恶性进展中作用，最近已被揭示。随着高通量测序技术的应用，在肿瘤组织中已经鉴定出大量的 circRNAs，一些 circRNAs 被证明是癌基因。在本研究中，我们通过高通量测序分析了结直肠癌（CRC）组织和正常相邻组织中的 circRNA 表达谱。我们专注于在 CRC 组织中表达显著增加的 circRNA_0000392，并进一步研究其在结直肠癌进展中的功能。
方法
通过 RNA 测序分析 6 对 CRC 组织和正常相邻组织中的 circRNA 表达谱。我们通过 qRT-PCR 在额外的样本中验证了鉴定出的差异表达 circRNAs，并选择 circRNA_0000392 来评估其与临床病理特征的关联。然后，我们在 CRC 细胞中敲低 circRNA_0000392，并通过功能实验研究体外和体内的影响。进行双荧光素酶和 RNA 下拉测定以进一步探索下游潜在的分子机制。
结果
circRNA_0000392 在 CRC 中与正常相邻组织和细胞系相比明显上调。circRNA_0000392 的表达水平与 CRC 的恶性进展呈正相关。功能研究表明，降低 circRNA_0000392 的表达可在体外和体内均抑制 CRC 的增殖和侵袭。机制上，circRNA_0000392 可以作为 miR-193a-5p 的海绵，并调节 PIK3R3 的表达，影响 CRC 细胞中 AKT-mTOR 通路的激活。
结论
circRNA_0000392 通过 CRC 细胞中的 miR-193a-5p/PIK3R3/Akt 轴发挥癌基因作用，表明 circRNA_0000392 是 CRC 治疗的潜在治疗靶点和 CRC 患者的预测标志物。
Zotero 插件