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The long noncoding RNA(lncRNA) small nucleolar RNA host gene 3(SNHG3) has been reported to be upregulated in colorectal cancer (CRC). However, its biological role and underlying mechanisms in CRC have not been well studied. The expression levels of SNHG3 were measured in CRC tissues and cell lines by real time quantitative PCR. Functional assays, including the cell counting Kit-8, wound healing and transwell invasion assays, were used to determine the effect of SNHG3 on CRC cell proliferation, migration and invasion,respectively. Furthermore, bioinformatics analysis, dual-Luciferase reporter assays and RNA immunoprecipitation were applied to determine the mechanism of SNHG3 in CRC. Mice xenograft models were established to assess the role of SNHG3 in CRC tumorigenicity and metastasis in vivo.The expression of SNHG3 was significantly upregulated in CRC tissues compared to adjacent normal tissues, which was positively correlated with advanced clinical stage, distant metastasis and poor overall survival. Functional experiments revealed that SNHG3 knockdown significantly decreased CRC growth and metastasis both in vitro and in vivo. Mechanistically, SNHG3 could bind to miR-539, thereby up-regulating the expression of its target gene runt-related transcription factor 2 (RUNX2), and play an oncogenic role in CRC progression. Our works suggest that lncRNA SNHG3 promotes CRC growth and metastasis via regulating miR-539/RUNX2 axis, suggesting that the SNHG3 might be a potential therapeutic target for CRC.

Emerging evidence has shown that microRNAs (miRNAs) such as miR-539 play critical roles in carcinogenesis and progression in many types of cancer, including human colorectal cancer (CRC). However, the roles and underlying mechanism of miR-539 in CRC have not been well identified. The aims of this study were, therefore, to investigate the regulatory role and potential mechanism of miR-539 in human CRC. Here, we show that miR-539 expression is downregulated in CRC tissues and cell lines. The expression level of miR-539 is inversely associated with advanced clinical stage and lymph node metastasis. In vitro studies reveal that overexpression of miR-539 inhibits CRC cell proliferation and colony formation as well as migration and invasion; in vivo results demonstrate that overexpression of miR-539 dramatically reduces CRC xenograft tumor growth. Moreover, runt-related transcription factor 2 ( RUNX2 ), a known oncogene, was identified as a target transcript of miR-539 in CRC by bioinformatic analysis, luciferase reporter assay, qPCR, and western blotting. RUNX2 expression levels were upregulated and inversely correlated with miR-539 expression in CRC tissues. Importantly, overexpression of RUNX2 without the 3′-untranslated region that is targeted by miR-539 partially reversed the inhibitory effect of miR-539 on CRC cell proliferation, migration, and invasion. Collectively, these findings demonstrate that miR-539 functions as a tumor suppressor in CRC, at least in part, by targeting RUNX2 , supporting the targeting of the novel miR-539 as a potentially effective therapeutic approach for treatment of CRC. [ABSTRACT FROM AUTHOR]