Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma.

IF 1.7 4区 生物学 Q3 BIOLOGY Open Life Sciences Pub Date : 2024-10-30 eCollection Date: 2024-01-01 DOI:10.1515/biol-2022-0975
Ming Yang, Zhaoyang Ke, Daji Wang
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Abstract

The resistance of tumor cells to chemotherapy drugs is a critical determinant in the recurrence and metastasis of nasopharyngeal carcinoma (NPC). Therefore, it is crucial to identify effective biotargets that can enhance the sensitivity of NPC cells to chemotherapy drugs. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) plays a central role in regulating chemotherapy resistance across various tumor types. However, its specific function in NPC cells remains unclear. This study reveals that hnRNPK is overexpressed in NPC tissues while weakly expressed in normal nasopharyngeal tissues. The expression level of hnRNPK is negatively associated with NPC patient survival. Importantly, hnRNPK is a key inducer of chemotherapy resistance in NPC, as evidenced by the significant increase in NPC cell sensitivity to cisplatin following hnRNPK knockdown. Mechanistically, hnRNPK induces chemotherapy resistance in NPC cells by suppressing the activation of the Akt/caspase 3 pathway. In NPC tumor-bearing mice, hnRNPK knockdown enhances the efficacy of cisplatin chemotherapy. Consequently, this work identifies a potential target for enhancing the sensitivity of NPC cells to chemotherapy.

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异质核糖核蛋白 K 是增强鼻咽癌化疗敏感性的潜在靶点。
肿瘤细胞对化疗药物的耐药性是鼻咽癌复发和转移的关键因素。因此,找到能提高鼻咽癌细胞对化疗药物敏感性的有效生物靶点至关重要。异质核糖核蛋白K(hnRNPK)在调节各种肿瘤类型的化疗耐药性方面发挥着核心作用。然而,它在鼻咽癌细胞中的具体功能仍不清楚。本研究揭示了 hnRNPK 在鼻咽癌组织中的过表达,而在正常鼻咽组织中的弱表达。hnRNPK 的表达水平与鼻咽癌患者的存活率呈负相关。重要的是,敲除 hnRNPK 后,鼻咽癌细胞对顺铂的敏感性显著增加,这证明 hnRNPK 是鼻咽癌化疗耐药性的关键诱导因子。从机理上讲,hnRNPK通过抑制Akt/caspase 3通路的激活来诱导鼻咽癌细胞产生化疗耐药性。在鼻咽癌肿瘤小鼠中,敲除hnRNPK可提高顺铂化疗的疗效。因此,这项研究为提高鼻咽癌细胞对化疗的敏感性找到了一个潜在靶点。
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来源期刊
CiteScore
2.50
自引率
4.50%
发文量
131
审稿时长
43 weeks
期刊介绍: Open Life Sciences (previously Central European Journal of Biology) is a fast growing peer-reviewed journal, devoted to scholarly research in all areas of life sciences, such as molecular biology, plant science, biotechnology, cell biology, biochemistry, biophysics, microbiology and virology, ecology, differentiation and development, genetics and many others. Open Life Sciences assures top quality of published data through critical peer review and editorial involvement throughout the whole publication process. Thanks to the Open Access model of publishing, it also offers unrestricted access to published articles for all users.
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