Circular RNA profiling identifies circ102049 as a key regulator of colorectal liver metastasis.
Circular RNA profiling identifies circ102049 as a key regulator of colorectal liver metastasis.
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环状RNA分析确定circ102049是结直肠肝转移的关键调节因子
DOI：
10.1002/1878-0261.12840
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发表时间：
2021-03
影响因子：
6.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Zhi Q;Wan D;Ren R;Xu Z;Guo X;Han Y;Liu F;Xu Y;Qin L;Wang Y
在这里，我们确定大约102049是转移性结直肠癌(CRC)的调节因子。在结直肠癌患者中，较高的102049水平与较差的临床结果相关，并以依赖于FRAS1的方式促进肝转移。Circ102049直接(作为miRNA海绵)和间接(修改RNA结合蛋白Dgcr8的亚细胞定位)调控FRAS1靶向miR-761和miR-192-3p的水平。环状RNA(CircRNA)在多种癌症的发生发展中起着重要作用。然而，CircRNA在结直肠癌肝转移中的作用和机制尚未完全阐明。我们通过CircRNA微阵列分析来筛选在结直肠癌肝转移病理中差异表达的CircRNA。应用实时荧光定量聚合酶链式反应技术检测hSA_CIRC_102049(约102049)在结直肠癌组织中的表达。用Circ102049过表达载体或小干扰(Si)RNA体外转染CRC细胞，观察其对细胞增殖的影响。通过生物信息学分析、荧光原位杂交、RNA免疫沉淀、RNA下拉和荧光素酶报告基因分析等方法，进一步证实了Circ102049、miR-761、miR-192-3p和FRAS1之间的相互关系。并对约102049在细胞质中募集和分布Dgcr8蛋白的机制进行了探讨。我们发现102049在有肝转移的原发结直肠癌中高表达，并且与结直肠癌患者的预后密切相关。Circ102049通过微(Mi)R-761/miR-192-3p-FRAS1依赖机制显著增强结直肠癌细胞的黏附、迁移和侵袭能力，促进结直肠癌进展。值得注意的是，由于Dgcr8蛋白的分布，大约102049也可能间接降低成熟miR-761和miR-192-3p在细胞质中的水平。此外，在体内实验中证实了Circ102049在促进结直肠癌肝转移中的作用。我们的发现提供了新的证据，表明Circ102049可能是结直肠癌的一个潜在的预后因素，并且Circ102049-miR-761/miR-192-3p-FRAS1轴可能是结直肠癌患者的抗转移靶点。
Here, we identify circ102049 as a regulator of metastatic colorectal cancer (CRC). High circ102049 levels were correlated with poor clinical outcomes in patients with CRC and promoted liver metastasis in an FRAS1‐dependent manner. Circ102049 regulated the levels of the FRAS1‐targeting miR‐761 and miR‐192‐3p both directly (acting as a miRNA sponge) and indirectly (modifying the subcellular localization of the RNA binding protein DGCR8). Circular RNA (circRNA) plays an essential role in the development and progression of various cancers. However, the functions and mechanisms of circRNA in colorectal liver metastasis have not been fully elucidated. We performed circRNA microarray analysis to screen differentially expressed circRNA in the pathology of colorectal liver metastasis. Quantitative real‐time PCR was used to detect the expression of hsa_circ_102049 (circ102049) in colorectal cancer (CRC) samples. CRC cells were transfected with circ102049 overexpression vector or small interfering (si)RNA to assess the effects of circ102049 in vitro. Bioinformatics analysis, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull‐down and luciferase reporter assays were conducted to confirm the relationship of circ102049, miR‐761, miR‐192‐3p and FRAS1. The mechanism by which circ102049 recruits and distributes DGCR8 protein in the cytoplasm was also investigated. We found that circ102049 was highly expressed in primary CRC tumors with liver metastasis and closely correlated with the prognosis of patients with CRC. Circ102049 significantly enhanced the adhesion, migration and invasion abilities of CRC cells, and promoted CRC progression via a micro (mi)R‐761/miR‐192‐3p‐FRAS1‐dependent mechanism. Notably, due to the distribution of DGCR8 protein, circ102049 may also indirectly reduce the levels of mature miR‐761 and miR‐192‐3p in the cytoplasm. In addition, the role of circ102049 in promoting colorectal liver metastasis was confirmed in vivo. Our findings provide new evidence that circ102049 may be a potential prognostic factor in CRC, and that the circ102049‐miR‐761/miR‐192‐3p–FRAS1 axis may be an anti‐metastatic target for CRC patients.
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影响因子：
45.3
作者：
Kopetz, Scott;Chang, George J.;McWilliams, Robert R.
通讯作者：
McWilliams, Robert R.
NSD2环状RNA通过靶向miR-199b-5p介导的DDR1和JAG1信号促进结直肠癌的转移
影响因子：
7.3
作者：
Chen, Liang-Yan;Zhi, Zheng;Li, Jian-Ming
通讯作者：
Li, Jian-Ming
DOI：
10.1016/j.jamcollsurg.2016.01.046
发表时间：
2016-05
影响因子：
5.2
作者：
Leal JN;Bressan AK;Vachharajani N;Gonen M;Kingham TP;D'Angelica MI;Allen PJ;DeMatteo RP;Doyle MB;Bathe OF;Greig PD;Wei A;Chapman WC;Dixon E;Jarnagin WR
通讯作者：
Jarnagin WR
影响因子：
3.7
作者：
Ren, Chunfeng;Zhang, Zhenmin;Wang, Wanhai
通讯作者：
Wang, Wanhai
影响因子：
3
作者：
Tessier, Aude;Sarreau, Melie;Guerrot, Anne-Marie
通讯作者：
Guerrot, Anne-Marie