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.
Mol Med Rep. 2021 Dec;24(6). doi: 10.3892/mmr.2021.12502. Epub 2021 Oct 22.
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. , 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.
抑癌基因腺瘤性结肠息肉病（APC）在结直肠癌（CRC）中经常失活或缺失。APC 的功能丧失会促进 β-连环蛋白的表达，β-连环蛋白对 CRC 的发展至关重要。由于 β-连环蛋白作为重要的转录因子，阻断 β-连环蛋白可能会产生副作用，包括组织内稳态和再生受损，从而限制了 β-连环蛋白抑制剂在 CRC 患者治疗中的应用。因此，鉴定 APC/β-连环蛋白的新型底物可能为开发有效的药物提供重要线索。在 CRC 细胞中，采用小干扰 RNA 技术和慢病毒介导的过表达，对 pleckstrin 2（PLEK2）进行敲低和过表达。采用细胞计数试剂盒-8 和集落形成测定、细胞周期分析和细胞凋亡检测，检测细胞增殖、细胞周期分布和细胞凋亡的能力。本研究表明，APC/β-连环蛋白信号级联在 CRC 细胞中转录激活 PLEK2。在 CRC 组织中 PLEK2 的表达明显增加。CRC 患者 APC 和 PLEK2 的表达呈负相关。过表达 PLEK2 增加了 CRC 细胞的增殖。在敲低 PLEK2 的细胞中观察到相反的结果。此外，PLEK2 促进细胞周期进程并抑制细胞凋亡。综上所述，上调 PLEK2 有助于 APC/β-连环蛋白信号通路激活的 CRC 增殖和集落形成。靶向 PLEK2 可能对治疗 APC/β-连环蛋白信号通路激活的 CRC 患者具有重要意义。
