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[基因在结直肠癌中高表达:其预后意义及作为治疗靶点的潜力]

[ gene is highly expressed in colorectal cancer: its prognostic implications and potential as a therapeutic target].

作者信息

Ji K, Yu G, Zhou L, Zhang T, Ling Q, Man W, Zhu B, Zhang W

机构信息

Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China.

Department of Colorectal Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200082, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2024 Sep 20;44(9):1685-1695. doi: 10.12122/j.issn.1673-4254.2024.09.08.

DOI:10.12122/j.issn.1673-4254.2024.09.08
PMID:39505336
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11744076/
Abstract

OBJECTIVE

To investigate the expression level of HNRNP A1 in colorectal cancer (CRC) and its prognostic implications.

METHODS

We investigated HNRNP A1 expression level in CRC using HPA, TIMER, and GEPIA databases and analyzed its association with Ki-67 and VEGFA expressions. Kaplan-Meier Plotter database was used to analyze the correlation of HNRNP A1 mRNA levels with the survival rates of CRC patients. Pathway enrichment analysis was performed for predicting the biological roles of HNRNP A1 in CRC progression. Immunohistochemistry and Western blotting were used to examine the protein levels of HNRNP A1 in CRC versus adjacent tissues, and TIMER was used for assessing its expression in the infiltrating immune cells. In RKO/Caco2 cells, the effects of lentivirus-mediated knockdown of HNRNP A1 on cell proliferation and migration were observed, and the inhibitory effect of VPC-80051 (a HNRNP A1 inhibitor) on cell proliferation was evaluated to assess its potential as a therapeutic agent.

RESULTS

HNRNP A1 was significantly overexpressed in CRC tissues and correlated with a poor prognosis of the patients. HNRNP A1 expression level was correlated with the infiltrating immune cells in CRC microenvironment and positively correlated with MKI67 and VEGFA expressions in CRC. A high HNRNP A1 expression predicted a in survival and progression-free survival of CRC patients and was involved in multiple biological processes related with CRC progression. In RKO/Caco2 cells, HNRNP A1 knockdown significantly suppressed cell proliferation and migration, and treatment with VPC-80051 also effectively inhibited CRC cell proliferation. Immunohistochemical study demonstrated a close correlation of HNRNP A1 overexpression with tumor stage of CRC.

CONCLUSION

HNRNP A1 is overexpressed in CRC tissues to modulate cell proliferation and migration and is correlated with a poorer prognosis. VPC-80051 can effectively inhibit CRC cell proliferation, suggesting the potential of HNRNP A1 as a therapeutic target for CRC.

摘要

目的

探讨HNRNP A1在结直肠癌(CRC)中的表达水平及其预后意义。

方法

我们利用HPA、TIMER和GEPIA数据库研究CRC中HNRNP A1的表达水平,并分析其与Ki-67和VEGFA表达的相关性。使用Kaplan-Meier Plotter数据库分析HNRNP A1 mRNA水平与CRC患者生存率的相关性。进行通路富集分析以预测HNRNP A1在CRC进展中的生物学作用。采用免疫组织化学和蛋白质印迹法检测CRC组织及癌旁组织中HNRNP A1的蛋白水平,并使用TIMER评估其在浸润免疫细胞中的表达。在RKO/Caco2细胞中,观察慢病毒介导的HNRNP A1敲低对细胞增殖和迁移的影响,并评估VPC-80051(一种HNRNP A1抑制剂)对细胞增殖的抑制作用,以评估其作为治疗药物的潜力。

结果

HNRNP A1在CRC组织中显著过表达,且与患者预后不良相关。HNRNP A1表达水平与CRC微环境中的浸润免疫细胞相关,且与CRC中MKI67和VEGFA表达呈正相关。高HNRNP A1表达预示CRC患者的总生存期和无进展生存期较差,且参与了与CRC进展相关的多个生物学过程。在RKO/Caco2细胞中,HNRNP A1敲低显著抑制细胞增殖和迁移,VPC-80051处理也有效抑制CRC细胞增殖。免疫组织化学研究表明HNRNP A1过表达与CRC的肿瘤分期密切相关。

结论

HNRNP A1在CRC组织中过表达,可调节细胞增殖和迁移,且与较差的预后相关。VPC-80051可有效抑制CRC细胞增殖,提示HNRNP A1作为CRC治疗靶点的潜力。

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本文引用的文献

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Analyzing the Effects of Single Nucleotide Polymorphisms on hnRNPA2/B1 Protein Stability and Function: Insights for Anticancer Therapeutic Design.分析单核苷酸多态性对hnRNPA2/B1蛋白稳定性和功能的影响:对抗癌治疗设计的启示
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Colorectal cancer: A health and economic problem.结直肠癌:一个健康和经济问题。
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NLRP12 downregulates the Wnt/β-catenin pathway via interaction with STK38 to suppress colorectal cancer.NLRP12 通过与 STK38 相互作用下调 Wnt/β-连环蛋白通路抑制结直肠癌。
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A comprehensive understanding of hnRNP A1 role in cancer: new perspectives on binding with noncoding RNA.对异质核糖核蛋白A1在癌症中作用的全面理解:与非编码RNA结合的新视角。
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HNRNPK/CLCN3 axis facilitates the progression of LUAD through CAF-tumor interaction.HNRNPK/CLCN3 轴通过 CAF-肿瘤相互作用促进 LUAD 的进展。
Int J Biol Sci. 2022 Oct 17;18(16):6084-6101. doi: 10.7150/ijbs.76083. eCollection 2022.
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RAB27A promotes the proliferation and invasion of colorectal cancer cells.RAB27A 促进结直肠癌细胞的增殖和侵袭。
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Managing the TME to improve the efficacy of cancer therapy.管理肿瘤微环境以提高癌症治疗的疗效。
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Emerging roles of hnRNP A2B1 in cancer and inflammation.hnRNP A2B1 在癌症和炎症中的新兴作用。
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Heterogeneous nuclear ribonucleoprotein K promotes the progression of lung cancer by inhibiting the p53-dependent signaling pathway.异质核核糖核蛋白 K 通过抑制 p53 依赖性信号通路促进肺癌的进展。
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