Volume 34, Issue 12 pp. 2126-2134
Gastroenterology

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

Yufeng Zhu

Yufeng Zhu

Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China

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Xiaojian Zhang

Xiaojian Zhang

Department of Thyroid Surgery, Taian Central Hospital, Taian, China

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Ming Qi

Ming Qi

Department of Ultrasound, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China

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Yong Zhang

Yong Zhang

The Second Department of General Surgery, Taian Central Hospital, Taian, China

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Feng Ding

Corresponding Author

Feng Ding

Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China

Correspondence

Feng Ding, Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, No.2, Section 5, People Street, Jinzhou, Liao Ning Province, 121000, China.

Email: [email protected]

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First published: 30 April 2019
Citations: 32
Declaration of conflict of interest: There are no conflicts of interest to declare.
Financial support: This work was supported by Science and Technology Plan Project of Liaoning Province, China (no. 20180540015).

Abstract

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.

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