High expression of atonal homolog 8 predicts a poor clinical outcome in patients with colorectal cancer and contributes to tumor progression

Ye,Mengsi; He,Yun; Lin,Hao; Yang,Shouxing; Zhou,Yuhui; Zhou,Lingling; Zhong,Jinwei; Lu,Guangrong; Zheng,Jihang; Xue,Zhan-Xiong; Cai,Zhen-Zhai

doi:10.3892/or.2017.5554

High expression of atonal homolog 8 predicts a poor clinical outcome in patients with colorectal cancer and contributes to tumor progression

Authors:
- Mengsi Ye
- Yun He
- Hao Lin
- Shouxing Yang
- Yuhui Zhou
- Lingling Zhou
- Jinwei Zhong
- Guangrong Lu
- Jihang Zheng
- Zhan-Xiong Xue
- Zhen-Zhai Cai
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Affiliations: Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Lucheng, Wenzhou, Zhejiang 325000, P.R. China, Department of Pathology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Lucheng, Wenzhou, Zhejiang 325000, P.R. China, Department of General Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Lucheng, Wenzhou, Zhejiang 325000, P.R. China
Published online on: April 5, 2017 https://doi.org/10.3892/or.2017.5554
Pages: 2955-2963

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Abstract

Hitherto, it has been identified that numerous basic-helix-loop-helix (bHLH) transcription factors play vital roles in tumor initiation and progression. Atonal homolog 8 (ATOH8) is a member of the bHLH family of transcription factors, which participates in embryogenesis and the development of various tissues. Several studies have demonstrated that ATOH8 is involved in the progression of malignancies; however, the effects of ATOH8 in colorectal cancer (CRC) remain unknown. The aim of the present study was to explore the expression and function of ATOH8 in CRC. The present study included 106 paired CRCs and peritumoral samples. The expression of ATOH8 was evaluated by immunohistochemistry, and the results were compared with the clinical outcomes of the patients. Furthermore, cell proliferation, cell cycle distribution, wound healing and cytotoxicity assays were performed in colon cancer cell line SW620. Immunohistochemical analyses revealed that the expression of ATOH8 in CRC tissues was significantly increased compared with the peritumoral tissues, and that the high expression of ATOH8 was associated with a high serum carcinoembryonic antigen (CEA) level and a worse overall survival. In vitro assays revealed that ATOH8 knockdown in colon cancer cells inhibited cell proliferation, induced cell cycle arrest at the S phase, and increased the percentage of apoptotic cells and sensitivity to 5-fluorouracil (5-FU). The present study suggests that ATOH8 promotes the progression of CRC and may potentially serve as a novel prognostic predictor and potential therapeutic target in CRC.

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