Circ-GALNT16 restrains colorectal cancer progression by enhancing the SUMOylation of hnRNPK.
Circ-GALNT16 restrains colorectal cancer progression by enhancing the SUMOylation of hnRNPK.
复制标题
DOI：
10.1186/s13046-021-02074-7
复制
发表时间：
2021-08-27
期刊：
影响因子：
--
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Peng C;Tan Y;Yang P;Jin K;Zhang C;Peng W;Wang L;Zhou J;Chen R;Wang T;Jin C;Ji J;Feng Y;Tang J;Sun Y
最近的研究已经调查了环状RNA（circRNA）作为多种癌症进展中的重要调节因子的作用。然而，circRNA的生物学功能及其调节结直肠癌（CRC）进展的潜在机制仍不清楚。通过微阵列和qRT-PCR鉴定了一种新的circRNA（circ-GALNT 16）。进行了一系列体外和体内表型实验以研究circ-GALNT 16在CRC中的作用。采用FISH、RNA pulldown、RIP、RNA测序、免疫共沉淀和ChIP等方法研究circ-GALNT 16在结直肠癌进展中的分子机制。Circ-GALNT 16在结直肠癌中表达下调，与预后不良呈负相关。Circ-GALNT 16在体外和体内抑制CRC细胞的增殖和转移能力。在机制上，circ-GALNT 16可以结合到异质核核糖核蛋白K（hnRNPK）的KH 3结构域，这促进了hnRNPK的SUMO化。此外，circ-GALNT 16可以通过促进hnRNPK的SUMO化来增强hnRNPK-p53复合物的形成。RNA测序结果表明，circ-GALNT 16的靶基因是丝氨酸蛋白酶抑制剂家族E成员1。拯救实验表明，circ-GALNT 16通过抑制SUMO特异性肽酶2介导的hnRNPK的去SUMO化，然后调节hnRNPK-p53转录复合物的序列特异性DNA结合能力来调节Serpine 1的表达。Circ-GALNT 16通过调节SENP 2介导的hnRNPK-p53转录复合物的序列特异性DNA结合能力来抑制Serpine 1表达，从而抑制CRC进展，并可能作为CRC的生物标志物和治疗靶点。在线版本包含补充材料，可通过10.1186/s13046-021-02074-7获得。
Recent studies have investigated the role of circular RNAs (circRNAs) as significant regulatory factors in multiple cancer progression. Nevertheless, the biological functions of circRNAs and the underlying mechanisms by which they regulate colorectal cancer (CRC) progression remain unclear. A novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of in vitro and in vivo phenotype experiments were performed to investigate the role of circ-GALNT16 in CRC. The FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were performed to investigate the molecular mechanisms of circ-GALNT16 in CRC progression. Circ-GALNT16 was downregulated in CRC and was negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastatic ability of CRC cells in vitro and in vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which promoted the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the formation of the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO-specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex. Circ-GALNT16 suppressed CRC progression by inhibiting Serpine1 expression through regulating the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might function as a biomarker and therapeutic target for CRC. The online version contains supplementary material available at 10.1186/s13046-021-02074-7.
登录
查看更多内容
影响因子：
9.7
作者：
Peng, Wen;Zhang, Chuan;Sun, Yueming
通讯作者：
Sun, Yueming
环状RNA circ-ERBIN通过miR-125a-5p和miR-138-5p/4EBP-1介导的不依赖帽的HIF-1 α翻译促进结直肠癌的生长和转移
影响因子：
37.3
作者：
Chen LY;Wang L;Ren YX;Pang Z;Liu Y;Sun XD;Tu J;Zhi Z;Qin Y;Sun LN;Li JM
通讯作者：
Li JM
影响因子：
14.8
作者：
Barysch, Sina V.;Dittner, Claudia;Melchior, Frauke
通讯作者：
Melchior, Frauke
影响因子：
14.9
作者：
Ostrowski, J;Kawata, Y;Bomsztyk, K
通讯作者：
Bomsztyk, K
影响因子：
7.5
作者：
Li, Sijing;Wei, Xiaohui;Sun, Li
通讯作者：
Sun, Li