Downregulation of miR-9 correlates with poor prognosis in colorectal cancer.

INTRODUCTION: microRNAs (miRNAs) are frequently dysregulated in many human cancers including colorectal cancer (CRC) and are useful candidate biomarkers in liquid biopsy of cancer for their stability in the blood. METHODS: We compared the expression of microRNA-9 (miR-9) in tissues (n = 357) and sera (n = 109) of CRC patients to determine whether miR-9 in serum reflects that in the cancer tissue in parallel. Also, we examined the miR-9 role in CRC by in vitro functional studies in four CRC cell lines. RESULTS: On multivariate analysis of colorectal cancer tissues and sera, miR-9 low expressions were significantly associated pN stage (tissues; p < 0.01, serum; p = 0.013), and clinical stage (tissues; p < 0.01, serum; p = 0.031). Moreover, patients with low miR-9 expression had shorter survival than those with high miR-9 expression (log-rank test, tissue; p = 0.021, serum; p = 0.011). miR-9 level in serum reflects that in the tumor. The CRC cells with low miR-9 expression was significantly increased cell proliferation, migration, invasion and colony formation than cells with high miR-9 expression. CONCLUSION: Serum miR-9 is an useful early detection marker in liquid biopsy of CRC and overexpression of miR-9 in CRC may be a novel prognostic marker as well.