MMRN1 Facilitates Renal Cell Carcinoma by Activating AMPK/MMPs Axis

IF 3.1 2区 医学 Q2 ONCOLOGY
Cancer Medicine Pub Date : 2025-06-30 DOI:10.1002/cam4.71013
Mingji Ye, Jian Cao, Zhihao Ming, Yu Xie
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Abstract

Background

MMRN1 is a metastasis-associated gene that is abnormally expressed in a variety of tumors. The present study aimed to explore the role of MMRN1 in renal cell carcinoma (RCC) and its related molecular mechanisms.

Methods

RNA sequencing was used to detect differential gene expression in RCC. Immunohistochemical (IHC) analysis identified the expression of MMRN1 in RCC. Statistical evaluations and the GEPIA database were conducted to examine the association between MMRN1 expression and the prognosis of RCC patients. The MTT assay was employed to assess cellular proliferative capacity, while the Transwell assay was used to evaluate metastasis. Additionally, subcutaneous tumor transplantation and lung metastasis assays in nude mice were performed to investigate the growth and metastasis of RCC cells in vivo.

Results

MMRN1 was significantly upregulated in RCC. The GEPIA database revealed an association between MMRN1 and distal metastasis, as well as poor prognosis in RCC patients. The overexpression of MMRN1 was found to enhance the proliferation and metastasis of RCC cells, whereas MMRN1 knockout was opposite. Additionally, MMRN1 overexpression facilitated the growth and metastasis of transplanted tumors in nude mice models. Mechanistically, MMRN1 overexpression activated the AMPK signaling pathway in RCC, and inhibition of this pathway mitigated the observed effects.

Conclusion

MMRN1 is an oncogene in RCC. MMRN1 activates MMPs through the AMPK pathway to promote the proliferation and invasion of RCC.

Abstract Image

MMRN1通过激活AMPK/MMPs轴促进肾细胞癌
MMRN1是一种在多种肿瘤中异常表达的转移相关基因。本研究旨在探讨MMRN1在肾细胞癌(RCC)中的作用及其相关分子机制。方法采用RNA测序法检测RCC中差异基因表达。免疫组化(IHC)分析确定了MMRN1在RCC中的表达。通过统计评估和GEPIA数据库来检验MMRN1表达与RCC患者预后之间的关系。MTT法用于评估细胞增殖能力,Transwell法用于评估转移。另外,通过裸鼠皮下肿瘤移植和肺转移实验,研究RCC细胞在体内的生长和转移情况。结果MMRN1在RCC中表达显著上调。GEPIA数据库揭示了MMRN1与RCC患者远端转移以及预后不良之间的关联。研究发现,过表达MMRN1可促进RCC细胞的增殖和转移,而敲除MMRN1则相反。此外,在裸鼠模型中,MMRN1过表达促进移植瘤的生长和转移。在机制上,MMRN1过表达激活了RCC中AMPK信号通路,抑制该通路减轻了观察到的效果。结论MMRN1是膀胱癌的致癌基因。MMRN1通过AMPK途径激活MMPs,促进RCC的增殖和侵袭。
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来源期刊
Cancer Medicine
Cancer Medicine ONCOLOGY-
CiteScore
5.50
自引率
2.50%
发文量
907
审稿时长
19 weeks
期刊介绍: Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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