Open Access iconOpen Access

ARTICLE

Macrophage-derived exosomal miR-342-3p promotes the progression of renal cell carcinoma through the NEDD4L/CEP55 axis

JIAFU FENG1,2,#,*, BEI XU1,2,#, CHUNMEI DAI1,2,#, YAODONG WANG1,4, GANG XIE1,5, WENYU YANG1,2, BIN ZHANG1,2, XIAOHAN LI6, JUN WANG3

1 NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, 621000, China
2 Departments of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China
3 Medical Technology Institute, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
4 Departments of Urology Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China
5 Departments of Pathology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China
6 Department of Medical Laboratory, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

* Corresponding Author: JIAFU FENG. Email: email
# These authors contributed equally to this work and should be all considered as the first authors

Oncology Research 2021, 29(5), 331-349. https://doi.org/10.32604/or.2022.03554

Abstract

Due to its difficulty in early diagnosis and lack of sensitivity to chemotherapy and radiotherapy, renal cell carcinoma (RCC) remains to be a frequent cause of cancer-related death. Here, we probed into new targets for its early diagnosis and treatment for RCC. microRNA (miRNA) data of M2-EVs and RCC were searched on the Gene Expression Omnibus database, followed by the prediction of the potential downstream target. Expression of target genes was measured via RT-qPCR and Western blot, respectively. M2 macrophage was obtained via flow cytometry with M2-EVs extracted. The binding ability of miR-342-3p to NEDD4L and to CEP55 ubiquitination was studied with their roles in the physical abilities of RCC cells assayed. Subcutaneous tumor-bearing mouse models and lung metastasis models were prepared to observe in vivo role of target genes. M2-EVs induced RCC growth and metastasis. miR-342-3p showed high expression in both M2-EVs and RCC cells. M2-EVs carrying miR-342-3p promoted RCC cell abilities to proliferate, invade and migrate. In RCC cells, M2-EV-derived miR-342-3p could specifically bind to NEDD4L and consequently elevate CEP55 protein expression via suppressing NEDD4L, thereby exerting tumor-promoting effects. CEP55 could be degraded by ubiquitination under the function of NEDD4L, and miR-342-3p delivered by M2-EVs facilitated the RCC occurrence and development by activating the PI3K/AKT/mTOR signaling pathway. In conclusion, M2-EVs promote RCC growth and metastasis by delivering miR-342-3p to suppress NEDD4L and subsequently inhibit CEP55 ubiquitination and degradation via activation of the PI3K/AKT/mTOR signaling pathway, strongly driving the proliferative, migratory and invasive of RCC cells.

Keywords


Cite This Article

APA Style
FENG, J., XU, B., DAI, C., WANG, Y., XIE, G. et al. (2021). Macrophage-derived exosomal mir-342-3p promotes the progression of renal cell carcinoma through the NEDD4L/CEP55 axis. Oncology Research, 29(5), 331-349. https://doi.org/10.32604/or.2022.03554
Vancouver Style
FENG J, XU B, DAI C, WANG Y, XIE G, YANG W, et al. Macrophage-derived exosomal mir-342-3p promotes the progression of renal cell carcinoma through the NEDD4L/CEP55 axis. Oncol Res. 2021;29(5):331-349 https://doi.org/10.32604/or.2022.03554
IEEE Style
J. FENG et al., "Macrophage-derived exosomal miR-342-3p promotes the progression of renal cell carcinoma through the NEDD4L/CEP55 axis," Oncol. Res., vol. 29, no. 5, pp. 331-349. 2021. https://doi.org/10.32604/or.2022.03554



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 1180

    View

  • 667

    Download

  • 0

    Like

Share Link