SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop.
SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop.
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SNHG17通过调节Trim23-PES1轴和miR-339-5p-FOSL2-SNHG17正反馈环促进结直肠肿瘤发生和转移
DOI：
10.1186/s13046-021-02162-8
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发表时间：
2021-11-15
期刊：
影响因子：
--
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Bian Z;Zhou M;Cui K;Yang F;Cao Y;Sun S;Liu B;Gong L;Li J;Wang X;Li C;Yao S;Yin Y;Huang S;Fei B;Huang Z
背景小核仁 RNA 宿主基因 (SNHG) 长非编码 RNA (lncRNA) 在人类癌症中经常失调，并参与肿瘤的发生和进展。 SNHG17 已被报道为多种癌症类型的候选癌基因，然而，其在结直肠癌 (CRC) 中的调节作用尚不清楚。方法通过 RT-qPCR 或生物信息学分析评估多个 CRC 队列中的 SNHG17 表达。使用细胞计数试剂盒-8 (CCK-8) 和集落形成测定评估细胞活力。通过 Transwell 测定评估细胞迁移性和侵袭性。应用肿瘤异种移植和转移模型来证实SNHG17对体内CRC肿瘤发生和转移的影响。免疫组织化学染色用于测量癌组织中的蛋白质表达。使用 RNA Pull-down、RNA 免疫沉淀、染色质免疫沉淀和双荧光素酶测定来研究 SNHG17 在 CRC 中的分子机制。结果使用多个队列，我们证实 SNHG17 在 CRC 中异常上调，并与较差的生存率相关。体外和体内功能测定表明SNHG17促进CRC增殖和转移。 SNHG17 通过抑制 Trim23 介导的 PES1 泛素化来阻止 PES1 降解。 SNHG17 通过海绵 miR-339-5p 上调 FOSL2，FOSL2 转录激活 SNHG17 表达，揭示 SNHG17-miR-339-5p-FOSL2-SNHG17 正反馈环。结论我们将 SNHG17 鉴定为 CRC 中的致癌 lncRNA，并将 SNHG17 的异常上调鉴定为 CRC 的预后危险因素。我们的机制研究首次证明，SNHG17 通过两种不同的调节机制（SNHG17-Trim23-PES1 轴和 SNHG17-miR-339-5p-FOSL2-SNHG17 正反馈环）促进肿瘤生长和转移，这可用于 CRC 治疗。
BackgroundSmall nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear.MethodsSNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC.ResultsUsing multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop.ConclusionsWe identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.
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影响因子：
4.6
作者：
Bian Z;Jin L;Zhang J;Yin Y;Quan C;Hu Y;Feng Y;Liu H;Fei B;Mao Y;Zhou L;Qi X;Huang S;Hua D;Xing C;Huang Z
通讯作者：
Huang Z
PES1 的 SUMO 化通过抑制其泛素化来上调其稳定性和功能
影响因子：
--
作者：
Li S;Wang M;Qu X;Xu Z;Yang Y;Su Q;Wu H
通讯作者：
Wu H
DOI：
10.1083/jcb.200501141
发表时间：
2005-08-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hölzel M;Rohrmoser M;Schlee M;Grimm T;Harasim T;Malamoussi A;Gruber-Eber A;Kremmer E;Hiddemann W;Bornkamm GW;Eick D
通讯作者：
Eick D
影响因子：
3.7
作者：
Li, Shuo;Fang, Xue-dong;Fei, Bing-Yuan
通讯作者：
Fei, Bing-Yuan
影响因子：
6.4
作者：
Qiao, Chunyan;Qiao, Tianyi;Zheng, Mengdan
通讯作者：
Zheng, Mengdan