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HNRNPA2B1 and HNRNPR stabilize ASCL1 in an m6A-dependent manner to promote neuroblastoma progression
Ting Hu1, Chong Zeng2, Zhihao Song1
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
Biochimica Et Biophysica Acta. Molecular Basis of Disease
|February 8, 2024
Summary
Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) and HNRNPR stabilize ASCL1 mRNA via m6A modification, promoting neuroblastoma progression. This HNRNPA2B1/HNRNPR/ASCL1 axis presents a potential therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- The roles of HNRNPA2B1 and HNRNPR in neuroblastoma are unclear, particularly regarding their dependence on m6A modification and involvement with ASCL1.
- Understanding the regulatory mechanisms of ASCL1 mRNA stability is crucial for neuroblastoma research.
Purpose of the Study:
- To investigate the m6A-dependent binding of HNRNPA2B1 and HNRNPR to ASCL1 mRNA.
- To elucidate the expression, clinical significance, and functional roles of HNRNPA2B1 and HNRNPR in neuroblastoma.
- To identify the HNRNPA2B1/HNRNPR/ASCL1 axis as a potential therapeutic target.
Main Methods:
- Investigated m6A modification of ASCL1 mRNA mediated by METTL14.
- Assessed the binding of HNRNPA2B1 and HNRNPR to ASCL1 mRNA using m6A site mutations.
- Analyzed the interaction between HNRNPR and IGF2BP1.
- Performed knockdown and overexpression experiments to evaluate cellular functions.
Main Results:
- METTL14 mediates ASCL1 mRNA m6A modification, enhancing its stability.
- HNRNPA2B1 and HNRNPR bind to ASCL1 mRNA in an m6A-dependent manner, stabilizing it.
- HNRNPA2B1 and HNRNPR knockdown inhibited neuroblastoma cell growth and invasion, effects reversed by ASCL1 overexpression.
- High expression of HNRNPA2B1 and HNRNPR correlates with ASCL1 expression and poorer prognosis in neuroblastoma.
Conclusions:
- HNRNPA2B1 and HNRNPR stabilize ASCL1 mRNA through an m6A-dependent mechanism, promoting neuroblastoma progression.
- The identified HNRNPA2B1/HNRNPR/ASCL1 regulatory axis offers a novel therapeutic strategy for neuroblastoma.
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