Chongwen Wang
1,2*
Zheng Zhou
1*The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1461546
MAFG-DT promotes prostate cancer bone metastasis through activation of the Wnt/β-catenin pathway
Provisionally accepted- 1 Department of Orthopaedics, Chengdu Fifth People's Hospital, Chengdu, China
- 2 Chengdu Fifth People's Hospital, Chengdu, Sichuan Province, China
Backgroud: Prostate cancer (PCa) ranks as the second leading cause of cancer-related mortality among men. Long non-coding RNAs (lncRNAs) are known to play a regulatory role in the development of various human cancers. LncRNA MAFG-divergent transcript (MAFG-DT) was reported to play a crucial role in tumor progression of multiple human cancers, such as pancreatic cancer, colorectal cancer, bladder cancer, and gastric cancer. Nevertheless, the specific function of MAFG-DT in the context of bone metastasis in PCa remains inadequately understood. Methods: The expression level of MAFG-DT was analyzed in published datasets and further confirmed in clinical samples and cell lines by RT-qPCR and in situ hybridization assays. Additionally, we further examined the effect of MAFG-DT on cell proliferation, migration, invasion and bone metastasis through CCK8, EdU, colony formation, transwell assays and bone metastasis model with intracardiac injection. Subquently, the specific mechanism of MAFG-DT in PCa was investigated by RIP, ChIP, bioinformatic analysis and luciferase reporter assays. Results: We found that MAFG-DT expression was significantly upregulated in PCa tissues exhibiting bone metastasis. Elevated levels of MAFG-DT expression were found to be positively associated with poor prognostic outcomes in PCa patients. Functionally, the knockdown of MAFG-DT resulted in a pronounced inhibition of cellular proliferation, migration, invasion, and bone metastasis. Moreover, it was demonstrated that MAFG-DT enhanced the expression of FZD4 and FZD5 mRNAs by sequestering miR-24-3p, thereby activating the Wnt/β-catenin signaling pathway. Additionally, the transcription factor MAFG was found to transcriptionally activate MAFG-DT in PCa. Conclusion: This study confirmes the oncogenic role of MAFG/MAFG-DT/ miR-24-3p/Wnt/β-catenin in PCa, which suggests that MAFG-DT could serve as a potential therapeutic target for PCa.
Keywords: MAFG-DT, prostate cancer, Wnt/β-Catenin pathway, miR-24-3p, FZD4, FZD5
Received: 08 Jul 2024; Accepted: 29 Nov 2024.
Copyright: © 2024 Wang, Zhou, Ye, Zhou, Wang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chongwen Wang, Department of Orthopaedics, Chengdu Fifth People's Hospital, Chengdu, China
Zheng Zhou, Department of Orthopaedics, Chengdu Fifth People's Hospital, Chengdu, China
Yongjie Ye, Department of Orthopaedics, Chengdu Fifth People's Hospital, Chengdu, China
Liqiang Zhou, Department of Orthopaedics, Chengdu Fifth People's Hospital, Chengdu, China
Jialun Wang, Department of Orthopaedics, Chengdu Fifth People's Hospital, Chengdu, China
Zhi Zhang, Department of Orthopaedics, Chengdu Fifth People's Hospital, Chengdu, China
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