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Pokemon inhibits Bim transcription to promote the proliferation, anti-anoikis, invasion, histological grade, and dukes stage of colorectal neoplasms

  • Yan Wang,
  • Huiling Zeng,
  • Li Li,
  • Jizhen Liu,
  • Jiantao Lin,
  • Yanhong Bie,
  • Sen Wang,
  • Xiaoguang Cheng,
  • Bayaer Nashun,
  • Yunhong Yao,
  • Xinrong Hu,
  • Yi Zhao

摘要

Purpose

This study aims to determine whether Pokemon regulates Bim activity in colorectal carcinoma (CRC) carcinogenesis.

Methods

Clinical tissue samples were analyzed to detect the expression and clinicopathological significance of Pokemon and Bim in CRC. Proliferation, apoptosis, and invasion assays were conducted to identify the regulatory effect of Pokemon on Bim. The combined treatment effects of Pokemon knockdown and diamminedichloroplatinum (DDP) were also examined.

Results

Immunohistochemical analysis of 80 samples of colorectal epithelia (CRE), 80 cases of colorectal adenoma (CRA), and 160 of CRC samples revealed protein expression rates of 23.8%, 38.8%, and 70.6% for Pokemon, and 88.8%, 73.8%, and 31.9% for Bim, respectively. A significant negative correlation was observed between Pokemon and Bim expression across the CRE, CRA, and CRC lesion stages. In CRC, higher Pokemon and lower Bim expression correlated with higher histological grades, advanced Dukes stages, and increased cancer invasion. In both LoVo and HCT116 cells, overexpression of Pokemon significantly reduced Bim expression, leading to increased proliferation, resistance to anoikis, and cell invasion. Additionally, Pokemon overexpression significantly decreased DDP-induced Bim expression, reduction of anti-apoptosis and invasion, whereas Pokemon knockdown resulted in the opposite effects.

Conclusion

These findings suggest that Pokemon inhibits Bim transcription, thereby promoting CRC proliferation, resistance to apoptosis, invasion, and advancing histological grade and Dukes staging. Pokemon knockdown enhances the therapeutic efficacy of DDP in the treatment of CRC.