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Background and AimWe previously discovered that tumor suppressor candidate 3 (TUSC3) was overexpressed and predicted worse prognosis in colon cancer patients. However, the mechanisms of upregulation of TUSC3 in colon cancer remained unclear.MethodsMiR‐873‐5p was predicted and identified as the regulator of TUSC3 via online programs and luciferase reporter assays. The roles of miR‐873‐5p in regulating colon cancer cell proliferation, colony formation, and invasion were evaluated in vitro. Animal studies were performed to investigate the effects of miR‐873‐5p on proliferation and lung metastasis. Moreover, the miR‐873‐5p/TUSC3 related signaling pathway and the prognostic value of combining miR‐873‐5p and TUSC3 for colon cancer patients were also explored.ResultsHere, we identified miR‐873‐5p as a novel regulator of TUSC3 in colon cancer. Functionally, ectopic expression or silencing of miR‐873‐5p, respectively, inhibited or promoted colon cancer cells proliferation, colony formation, and invasion, as well as prevented or enhanced the metastasis of colon cancer cells in vitro and in vivo.Molecularly, miR‐873‐5p functioned as a tumor suppressor by inhibiting the TUSC3/AKT pathway. Overexpression or silencing of TUSC3 could partially reverse the effects of the overexpression or repression of miR‐873‐5p on colon cancer progression caused by activation of the AKT pathway. Clinically, low miR‐873‐5p expression predicted poor survival in colon cancer patients, especially combined with high TUSC3 expression.ConclusionsWe identified miR‐873‐5p as a tumor suppressor, which acts by directly repressing TUSC3 in colon cancer.

Accumulating evidence has implicated that constitutive activation of signal transducer and activator of transcription protein 3 (STAT3) may be a major oncogenic factor involved in hepatocellular carcinoma (HCC) development. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) has been shown to be a tumor suppressor associated with growth control and suppression of STAT3 activity. The downregulation of GRIM-19 expression has been shown in a number of human tumor types, and it has been correlated with hyperactivation of STAT3. However, the role of GRIM-19 in the pathogenesis of HCC has not been evaluated. The aim of our study was to evaluate GRIM-19 expression levels and investigate their correlation with phosphorylated STAT3 (p-STAT3) levels in HCC. GRIM-19 and p-STAT3 expression levels were analyzed in HCC and adjacent nontumorous liver tissues (ANLT) by immunohistochemistry, western blot analysis, and RT-PCR. GRIM-19 protein expression was predominantly located in the cytoplasm with weak staining in the nucleus in ANLT, but only located in the cytoplasm in HCC tissues. HCC samples exhibited low levels of GRIM-19 and moderate to high levels of p-STAT3 expression. In contrast, ANLT was characterized by high levels of GRIM-19 and low levels of p-STAT3 expression. Downregulation of GRIM-19 was closely correlated with increased histological grade in HCC. GRIM-19 expression is closely correlated with histological grading and p-STAT3 in HCC. Thus, the potential role of GRIM-19 in HCC development may be through these correlations.