Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

Lei Zheng, Jia Lu, Da-Lu Kong
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Abstract

BACKGROUND Cyclin-dependent kinase 9 (CDK9) expression and autophagy in colorectal cancer (CRC) tissues has not been widely studied. CDK9, a key regulator of transcription, may influence the occurrence and progression of CRC. The expression of autophagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC. Under normal physiological conditions, autophagy can inhibit tumorigenesis, but once a tumor forms, autophagy may promote tumor growth. Therefore, understanding the relationship between autophagy and cancer, particularly how autophagy promotes tumor growth after its formation, is a key motivation for this research. AIM To investigate the relationship between CDK9 expression and autophagy in CRC, assess differences in autophagy between left and right colon cancer, and analyze the associations of autophagy-related genes with clinical features and prognosis. METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9. We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues. RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer, and autophagy might be involved in the occurrence of chemotherapy resistance. Further analysis of the relationship between the expression of autophagy-related genes CDK9, ABCG2 , and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer. CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.
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结肠癌中细胞周期蛋白依赖性激酶 9 的表达与自噬水平呈正相关
背景循环蛋白依赖性激酶9(CDK9)在结直肠癌(CRC)组织中的表达和自噬尚未得到广泛研究。CDK9 是转录的关键调控因子,可能会影响 CRC 的发生和进展。自噬相关基因 BECN1 和耐药因子 ABCG2 的表达也可能在 CRC 中发挥作用。在正常生理条件下,自噬可以抑制肿瘤发生,但一旦肿瘤形成,自噬可能会促进肿瘤生长。因此,了解自噬与癌症之间的关系,尤其是自噬如何在肿瘤形成后促进肿瘤生长,是本研究的关键动机。目的 探讨 CDK9 表达与 CRC 自噬的关系,评估左右结肠癌自噬的差异,分析自噬相关基因与临床特征和预后的关系。方法 我们收集了有肝转移的结肠癌患者的肿瘤组织和癌旁组织,观察 CDK9 水平高的组织和 CDK9 水平低的组织的自噬水平。我们还收集了肝转移的左右结肠癌患者的原发组织,比较肿瘤和癌旁组织的自噬水平以及 BECN1 和 ABCG2 的表达。结果 左右结肠癌的自噬发生率和 BECN1、ABCG2 的表达不同,自噬可能与化疗耐药的发生有关。进一步分析自噬相关基因 CDK9、ABCG2 和 BECN1 的表达与结直肠癌临床特征和预后的关系发现,CDK9 的高表达表明结直肠癌的预后较差。结论 本研究为进一步研究 CDK9 抑制剂和自噬抑制剂联合治疗 CRC 患者奠定了基础。
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