SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop

Journal of Experimental & Clinical Cancer Research

Bojian Fei¹  Shenglin Huang²  Jiuming Li³  Xue Wang³  Liang Gong³  Kaisa Cui⁴  Yulin Cao⁴  Yuan Yin⁴  Fan Yang⁴  Bingxin Liu⁴  Shengbai Sun⁴  Zehua Bian⁴  Chaoqun Li⁴  Mingyue Zhou⁴  Surui Yao⁴  Zhaohui Huang⁵ 

[1] Department of Surgical Oncology, Affiliated Hospital of Jiangnan University, 200 Hui He Road, 214062, Wuxi, Jiangsu, China;Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China;Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, 214122, Wuxi, Jiangsu, China;Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, 214062, Wuxi, Jiangsu, China;Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, 214062, Wuxi, Jiangsu, China;Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, 214122, Wuxi, Jiangsu, China;

关键词: CRC;    lncRNA;    SNHG17;    PES1;    FOSL2;    miR-339-5p;   

DOI  :  10.1186/s13046-021-02162-8

来源: Springer

【 摘 要 】

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.

【 授权许可】

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