The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis 06 Biological Sciences 0604 Genetics

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Abstract

Background: Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles during the initiation and progression of cancers. In this study, we report that the small nucleolar RNA host gene 1 (SNHG1) is involved in colorectal cancer progression. Methods: We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer. The effects of SNHG1 on colorectal cancer were investigated through in vitro and in vivo assays (i.e., CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and western blot). The mechanism of SNHG1 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay. Results: Our analysis revealed that SNHG1 was upregulated in human colorectal cancer tissues, and high SNHG1 expression was associated with reduced patient survival. We also found that high SNHG1 expression was partly induced by SP1. Moreover, SNHG1 knockdown significantly repressed colorectal cancer cells growth both in vitro and in vivo. Mechanistic investigations demonstrated that SNHG1 could directly interact with Polycomb Repressive Complex 2 (PRC2) and modulate the histone methylation of promoter of Kruppel like factor 2 (KLF2) and Cyclin dependent kinase inhibitor 2B (CDKN2B) in the nucleus. In the cytoplasm, SNHG1 acted as a sponge for miR-154-5p, reducing its ability to repress Cyclin D2 (CCND2) expression. Conclusions: Taken together, the results of our studies illuminate how SNHG1 formed a regulatory network to confer an oncogenic function in colorectal cancer and suggest that SNHG1 may serve as a potential target for colorectal cancer diagnosis and treatment.

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Xu, M., Chen, X., Lin, K., Zeng, K., Liu, X., Pan, B., … Wang, S. (2018). The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis 06 Biological Sciences 0604 Genetics. Molecular Cancer, 17(1). https://doi.org/10.1186/s12943-018-0894-x

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