Pleckstrin 2 is a potential drug target for colorectal carcinoma with activation of APC/β‑catenin

Chai,Bao; Guo,Yarong; Zhu,Na; Jia,Junmei; Zhang,Zhuowei; Ping,Mei; Jia,Kai; Cui,Xiaolong; Suo,Yuhong

doi:10.3892/mmr.2021.12502

Pleckstrin 2 is a potential drug target for colorectal carcinoma with activation of APC/β‑catenin

Authors:
- Bao Chai
- Yarong Guo
- Na Zhu
- Junmei Jia
- Zhuowei Zhang
- Mei Ping
- Kai Jia
- Xiaolong Cui
- Yuhong Suo
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Affiliations: Department of Gastroenterology, Shanxi Academy of Medical Science, Shanxi Bethune Hospital, Taiyuan, Shanxi 030032, P.R. China, Department of Oncology, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Medical Imaging Department, Shanxi Medical University, Taiyuan, Shanxi 030031, P.R. China, Department of Surgery, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030031, P.R. China, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300181, P.R. China
Published online on: October 19, 2021 https://doi.org/10.3892/mmr.2021.12502
Article Number: 862
Copyright: © Chai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The tumor suppressor gene adenomatous polyposis coli (APC) is frequently inactivated or absent in colorectal carcinoma (CRC). Loss‑of‑function of APC promotes the expression of β‑catenin, which is critical for CRC development. Since β‑catenin acts as an important transcription factor, blockage of β‑catenin may have side effects, including impairment of tissue homeostasis and regeneration, thus limiting the application of β‑catenin inhibitors for the treatment of patients with CRC. Therefore, identifying a novel substrate of APC/β‑catenin may provide essential clues to develop effective drugs. Small interfering RNA technology and lentivirus‑mediated overexpression were performed for knockdown and overexpression of pleckstrin 2 (PLEK2) in CRC cells. Cell Counting Kit‑8 and colony formation assays, and cell cycle analysis and cell apoptosis detection were used to detect the capacity of cell proliferation, cell cycle distribution and apoptosis. The present study demonstrated that the APC/β‑catenin signaling cascade transcriptionally activated PLEK2 in CRC cells. PLEK2 expression was markedly increased in CRC tissues. There was an inverse correlation between APC and PLEK2 expression in patients with CRC. In vitro, overexpression of PLEK2 increased the proliferation of CRC cells. Opposite results were observed in the cells with knockdown of PLEK2. Furthermore, PLEK2 promoted cell cycle progression and suppressed apoptosis. In summary, upregulation of PLEK2 contributed to CRC proliferation and colony formation activated by the APC/β‑catenin signal pathway. Targeting PLEK2 may be important for the treatment of patients with CRC with activation of the APC/β‑catenin signaling pathway.

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