miR‐873‐5p inhibits the progression of colon cancer via repression of tumor suppressor candidate 3/AKT signaling.

Zhu, Yufeng; Zhang, Xiaojian; Qi, Ming; Zhang, Yong; Ding, Feng

Background and Aim: We 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. Methods: MiR‐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. Results: Here, 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. Conclusions: We identified miR‐873‐5p as a tumor suppressor, which acts by directly repressing TUSC3 in colon cancer.

COLON cancer; COLON cancer prognosis; CANCER cell proliferation; CANCER invasiveness; TUMORS

Journal of Gastroenterology & Hepatology, 2019, Vol 34, Issue 12, p2126

0815-9319

Academic Journal

10.1111/jgh.14697