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

IF 2.7 3区 医学 Q3 ONCOLOGY Journal of Cancer Research and Clinical Oncology Pub Date : 2024-08-03 DOI:10.1007/s00432-024-05904-1
Yan Wang, Huiling Zeng, Li Li, Jizhen Liu, Jiantao Lin, Yanhong Bie, Sen Wang, Xiaoguang Cheng, Bayaer Nashun, Yunhong Yao, Xinrong Hu, Yi Zhao
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Abstract

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.

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Pokemon 可抑制 Bim 转录,从而促进结直肠肿瘤的增殖、抗肿瘤、侵袭、组织学分级和杜克分期。
目的:本研究旨在确定 Pokemon 是否调控 Bim 在结直肠癌(CRC)发生过程中的活性:方法:分析临床组织样本,检测 Pokemon 和 Bim 在 CRC 中的表达及临床病理学意义。方法:分析临床组织样本,检测 Pokemon 和 Bim 在 CRC 中的表达及临床病理意义;进行增殖、凋亡和侵袭试验,以确定 Pokemon 对 Bim 的调控作用。此外,还研究了 Pokemon 基因敲除和二氨基二氯铂(DDP)的联合治疗效果:对 80 份结直肠上皮(CRE)样本、80 例结直肠腺瘤(CRA)样本和 160 份 CRC 样本进行免疫组化分析后发现,Pokemon 蛋白表达率分别为 23.8%、38.8% 和 70.6%,Bim 蛋白表达率分别为 88.8%、73.8% 和 31.9%。在CRE、CRA和CRC病变阶段,Pokemon和Bim的表达呈明显负相关。在 CRC 中,较高的 Pokemon 和较低的 Bim 表达与较高的组织学分级、晚期 Dukes 阶段和癌症侵袭增加相关。在 LoVo 和 HCT116 细胞中,Pokemon 的过表达会显著降低 Bim 的表达,从而导致细胞增殖、抗 anoikis 能力和细胞侵袭能力增强。此外,过表达 Pokemon 能显著降低 DDP 诱导的 Bim 表达、抗凋亡和侵袭能力,而敲除 Pokemon 则产生相反的效果:这些研究结果表明,Pokemon能抑制Bim的转录,从而促进CRC的增殖、抗凋亡和侵袭,并提高组织学分级和Dukes分期。Pokemon基因敲除可增强DDP治疗CRC的疗效。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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