Colorectal cancer (CRC) is one of the most common malignant tumors and is associated with a high mortality rate due to the lack of specific biomarkers available for early diagnosis, targeted therapies, and prognostic surveillance. In the present study, we investigated the function of Numb and its underlying mechanism in CRC. Immunohistochemical staining and clinicopathological analysis were used to assess the expression of Numb and its clinical significance in patients with CRC. Quantitative real-time polymerase chain reaction, cell proliferation, Western blot, wound healing, Transwell, and TOP/FOP flash reporter assays were used to investigate the function of Numb and its underlying mechanism in CRC. Numb expression was downregulated and negatively correlated with the depth of invasion, tumor size, metastasis, TNM stage, and epithelial-to-mesenchymal transition (EMT) markers in CRC specimens. Numb negatively regulates the EMT, proliferation, invasion, migration, and the Wnt signaling pathway in vitro, as well as tumor growth and metastasis in vivo. Furthermore, activation of the Wnt signaling pathway by Wnt-3A negated the effect of Numb overexpression, whereas inhibition of the Wnt signaling pathway by IWR-1 impaired the effect of the Numb knockdown on the EMT. We concluded that Numb downregulation is a common event in patients with CRC and is closely correlated with cancer progression and a poor prognosis. Numb functions as a tumor suppressor in CRC, and its tumor suppressor function is mediated by negative regulation of the EMT through the Wnt signaling pathway. NEW & NOTEWORTHY We investigate the function of Numb and its underlying mechanism in colorectal cancer through quantitative real-time polymerase chain reaction, cell proliferation, Western blot, wound healing, Transwell, and TOP/FOP flash reporter assays. We conclude that Numb can negatively regulate the epithelial-to-mesenchymal transition through the Wnt signaling pathway to inhibit the development of colorectal cancer.

BackgroundAltered expression of miR-503 has been linked to human carcinogenesis. In this present study, we aimed to detect the potential for miR-503 as a novel biomarker for gastric cancer (GC) patients.Materials and methodsThe relative mRNA level of miR-503 in serum and tissue of 68 GC patients and serum of 32 healthy volunteers was determined by real-time reverse transcription quantitative polymerase chain reaction.ResultsThe miR-503 level was significantly lower in the tissue and serum of GC than their counterparts (all P<0.01). Downregulation of miR-503 was found to be corrected with more aggressive tumor. Patients in the high-miR-503 group showed significantly better overall survival compared to the low-miR-503 group (P=0.021). The serum miR-503 level in GC was inversely correlated with carcinoembryonic antigen (CEA) (r=−0.624, P<0.001). Furthermore, the area under the receiver operating characteristic curve for miR-503 discriminating GC patients from healthy individuals was 0.889 (P=0.006), with a sensitivity of 96.8% and a specificity of 79.4%, higher than that of CEA (area under the receiver operating characteristic curve =0.681, P=0.048).ConclusionThe present study suggests that the expression level of miR-503 may serve as prognostic and diagnostic biomarker for GC.

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