Chitinase-3 like-protein-1 (YKL-40) Promotes Anorectal Mucosal Melanoma Progression via the PI3K-AKT Signaling Pathway.

IF 1.9 4区医学 Q3 INTEGRATIVE & COMPLEMENTARY MEDICINE Alternative therapies in health and medicine Pub Date : 2024-10-01

Chaoyi Li, Yonggang Wang, Xiaodong Ren, Yaoping Li

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Abstract

Objective: Anorectal mucosal melanoma is a rare and aggressive cancer with limited treatment options. Investigating specific molecular pathways may provide insight into the development and progression of this cancer. This study aims to investigate the role of chitinase-3-like protein-1 (YKL-40) in promoting the development of anorectal mucosal melanoma through the PI3K-AKT signaling pathway.

Methods: Perianal cells from healthy volunteers and melanoma cells from patients with early, middle and advanced anorectal melanoma were obtained. Western blotting was performed to detect the protein expression of PI3K, AKT, and the downstream proteins mTOR, p-mTOR, ERK, and p-ERK, respectively. Subsequently, we constructed knockout and overexpression of YKL-40 melanoma cell lines, then used western blot assay to test for YKL-40, PI3K and AKT protein expression.

Results: A significant increase in the expression of PI3K, AKT, and the downstream proteins mTOR, pmTOR, ERK, and pERK was observed in melanoma cells, and the expression of these proteins increased with the development of melanoma. After YKL-40 was knocked out, PI3K and AKT expression decreased in melanoma cells in patients with advanced melanoma. On the contrary, PI3K and AKT protein expression increased significantly after YKL-40 overexpression.

Conclusion: There is a positive correlation between the expression levels of PI3K, AKT, mTOR, p-mTOR, ERK, and p-ERK and the stage of tumor development. The PI3K-AKT signaling pathway promotes the progress of anorectal mucosal melanoma. Chitinase-3-like protein-1 (YKL-40) regulates the progression of anorectal mucosal melanoma through the PI3K-AKT signaling pathway. Investigating specific molecular pathways may provide a better understanding of anorectal mucosal melanoma. The findings from this study could contribute to the development of new diagnosis and treatment strategies for this rare and aggressive cancer. Future research directions may include investigating other possible pathways involved in melanoma progression.

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几丁质酶-3 类似蛋白-1 (YKL-40) 通过 PI3K-AKT 信号通路促进肛门直肠粘膜黑色素瘤进展

目的：肛门直肠粘膜黑色素瘤是一种罕见的侵袭性癌症，治疗方案有限。研究特定的分子通路可能有助于深入了解这种癌症的发生和发展。本研究旨在探讨几丁质酶-3 样蛋白-1（YKL-40）通过 PI3K-AKT 信号通路在促进肛门直肠粘膜黑色素瘤发展中的作用：方法：获取健康志愿者的肛周细胞和早、中、晚期肛门直肠黑色素瘤患者的黑色素瘤细胞。方法：取健康志愿者的肛周细胞和早期、中期和晚期肛门直肠黑色素瘤患者的黑色素瘤细胞，分别用 Western 印迹法检测 PI3K、AKT 和下游蛋白 mTOR、p-mTOR、ERK 和 p-ERK 的蛋白表达。随后，我们构建了基因敲除和过表达YKL-40的黑色素瘤细胞系，然后用Western印迹法检测YKL-40、PI3K和AKT蛋白的表达：结果：在黑色素瘤细胞中观察到PI3K、AKT以及下游蛋白mTOR、pmTOR、ERK和pERK的表达明显增加，并且这些蛋白的表达随着黑色素瘤的发展而增加。敲除 YKL-40 后，晚期黑色素瘤患者的黑色素瘤细胞中 PI3K 和 AKT 的表达减少。相反，YKL-40过表达后，PI3K和AKT蛋白的表达明显增加：结论：PI3K、AKT、mTOR、p-mTOR、ERK 和 p-ERK 的表达水平与肿瘤的发展阶段呈正相关。PI3K-AKT信号通路促进了肛门直肠粘膜黑色素瘤的进展。几丁质酶-3样蛋白-1（YKL-40）通过PI3K-AKT信号通路调控肛门直肠粘膜黑色素瘤的进展。对特定分子通路的研究可能有助于更好地了解肛门直肠粘膜黑色素瘤。本研究的发现有助于为这种罕见的侵袭性癌症开发新的诊断和治疗策略。未来的研究方向可能包括调查黑色素瘤发展过程中可能涉及的其他通路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alternative therapies in health and medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-

CiteScore

0.90

自引率

0.00%

发文量

219

期刊介绍： Launched in 1995, Alternative Therapies in Health and Medicine has a mission to promote the art and science of integrative medicine and a responsibility to improve public health. We strive to maintain the highest standards of ethical medical journalism independent of special interests that is timely, accurate, and a pleasure to read. We publish original, peer-reviewed scientific articles that provide health care providers with continuing education to promote health, prevent illness, and treat disease. Alternative Therapies in Health and Medicine was the first journal in this field to be indexed in the National Library of Medicine. In 2006, 2007, and 2008, ATHM had the highest impact factor ranking of any independently published peer-reviewed CAM journal in the United States—meaning that its research articles were cited more frequently than any other journal’s in the field. Alternative Therapies in Health and Medicine does not endorse any particular system or method but promotes the evaluation and appropriate use of all effective therapeutic approaches. Each issue contains a variety of disciplined inquiry methods, from case reports to original scientific research to systematic reviews. The editors encourage the integration of evidence-based emerging therapies with conventional medical practices by licensed health care providers in a way that promotes a comprehensive approach to health care that is focused on wellness, prevention, and healing. Alternative Therapies in Health and Medicine hopes to inform all licensed health care practitioners about developments in fields other than their own and to foster an ongoing debate about the scientific, clinical, historical, legal, political, and cultural issues that affect all of health care.