Ythdf2-mediated fgf14-as2 decay promotes osteolytic metastasis of breast cancer by enhancing runx2 mrna translation

Ythdf2-mediated fgf14-as2 decay promotes osteolytic metastasis of breast cancer by enhancing runx2 mrna translation

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ABSTRACT BACKGROUND LncRNA FGF14-AS2 is a critical suppressor in breast cancer (BCa) metastasis. However, whether FGF14-AS2 plays a role in the bone metastasis of BCa remains unknown.


METHODS TRAP assay and intratibial injection were carried out to evaluate the role of FGF14-AS2 in BCa bone metastasis in vitro and in vivo. Polyribosome profiling was done to examine the


translation level. RNA pulldown combined with LC/MS was performed to identify the lncRNA-binding partner, RIP, dual-luciferase assay, and Co-IP assays as well to testify these physical


interactions. The prognostic value of FGF14-AS2 expression level in BCa patients was analysed using Kaplan–Meier Plotter. RESULTS We found that FGF14-AS2 suppresses osteoclast


differentiation and osteolytic metastasis of BCa. Mechanistically, FGF14-AS2 suppresses the translation of RUNX2 by inhibiting the assembly of eIF4E/eIF4G complex and the phosphorylation of


eIF4E, thereby reducing the transcription of RANKL, an essential regulator of osteoclast differentiation. Moreover, FGF14-AS2 is downregulated by YTHDF2-mediated RNA degradation in an


m6A-dependent manner. Clinically, patients with high YTHDF2 and low FGF14-AS2 expression levels showed worse distant metastasis-free survival (DMFS). CONCLUSIONS FGF14-AS2 plays a crucial


role in osteolytic metastasis, and may serve as a promising prognostic biomarker and therapeutic target for BCa bone metastasis. Access through your institution Buy or subscribe This is a


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NSUN2-MEDIATED M5C MODIFICATION OF EXOSOMAL LNCRNA MALAT1 INDUCED RANKL-MEDIATED BONE DESTRUCTION IN MULTIPLE MYELOMA Article Open access 02 October 2024 TUMOUR-DERIVED EXOSOMAL


LNCRNA-SOX2OT PROMOTES BONE METASTASIS OF NON-SMALL CELL LUNG CANCER BY TARGETING THE MIRNA-194-5P/RAC1 SIGNALLING AXIS IN OSTEOCLASTS Article Open access 02 July 2021 LSD1 MODULATES THE


BONE METASTASIS OF BREAST CANCER CELLS THROUGH HNRNPA2B1-MEDIATED SORTING OF EXOSOMAL MIRNAS Article Open access 06 March 2024 DATA AVAILABILITY All the data that support the findings of


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https://doi.org/10.1186/s13045-019-0839-x. Download references FUNDING This work was supported by grants from the National Natural Science Foundation of China (No. 81872389, 81570804 and


82072484); the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the Key Project of Science; the Major Projects of Science and Technology Development Fund


of Nanjing Medical University (No. NMUD2019004). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, 211166, Nanjing,


P.R. China Ming Zhang, Yucui Jin, Que Zheng, Mengying Xing, Yuting Tang, Yunfei Ma, Lingyun Li, Bing Yao & Changyan Ma * Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical


University, Longmian Road 101, 211166, Nanjing, P.R. China Ming Zhang & Changyan Ma * Division of Breast Surgery, the First Affiliated Hospital with Nanjing Medical University, Guangzhou


Road 300, 210029, Nanjing, Jiangsu Province, P.R. China Jue Wang * Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, 210029, Nanjing,


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CONTRIBUTIONS MZ, MX and YT performed the experiments. WJ provided the clinical samples. MZ performed the statistical analysis. YM and YJ performed the bioinformatic analyses. HW and QZ


reviewed the data. LL, BY, YJ and CM designed the research and drafted the manuscript. CORRESPONDING AUTHOR Correspondence to Changyan Ma. ETHICS DECLARATIONS COMPETING INTERESTS The authors


declare no competing interests. ETHICS APPROVAL AND CONSENT TO PARTICIPATE All procedures performed in studies involving human participants were in accordance with the ethical standards of


the Ethics Committee of Nanjing Medical University (Approval number: 2018-487) and with the Declaration of Helsinki and its later amendments or comparable ethical standards, and all patients


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FGF14-AS2 decay promotes osteolytic metastasis of breast cancer by enhancing RUNX2 mRNA translation. _Br J Cancer_ 127, 2141–2153 (2022). https://doi.org/10.1038/s41416-022-02006-y Download


citation * Received: 15 May 2022 * Revised: 26 September 2022 * Accepted: 27 September 2022 * Published: 10 October 2022 * Issue Date: 07 December 2022 * DOI:


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