IGF2BP2, an RNA‐binding protein regulates cell proliferation and osteogenic differentiation by stabilizing SRF mRNA

Osteoblast proliferation and osteogenic differentiation (OGD) are regulated by complex mechanisms. The roles in cell proliferation and OGD of RNA‐binding proteins in the insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP) family remain unclear. To elucidate this, we examined the differential expression of IGF2BP2 in OGD and osteoporosis, and the expression profile of IGF2BP2‐binding RNA in vitro. We screened the GEO database for differential expression of IGF2BP in OGD and osteoporosis, and verified the RNAs interacting with IGF2BP2 via RNA immunoprecipitation sequencing assays. The proliferation and OGD of IGF2BP2‐ and serum response factor (SRF)‐treated cells, and their regulatory mechanisms, were examined. IGF2BP2 was differentially expressed in OGD and osteoporosis. The RNA immunoprecipitation sequencing assay identified all of the RNAs that bind with IGF2BP2, and revealed SRF as a target of IGF2BP2. IGF2BP2 and SRF inhibition impaired MC3T3‐E1 cell growth but promoted OGD. The mRNA stability analysis revealed that IGF2BP2 enhanced SRF mRNA stability against degradation. In summary, IGF2BP2 is a potential biomarker and therapeutic target for osteoporosis and OGD.

[1]  N. Frey,et al.  SRF: a seriously responsible factor in cardiac development and disease , 2022, Journal of biomedical science.

[2]  A. Tabuchi,et al.  SRF in Neurochemistry: Overview of Recent Advances in Research on the Nervous System , 2022, Neurochemical Research.

[3]  S. Guil,et al.  The IGF2BP family of RNA binding proteins links epitranscriptomics to cancer. , 2022, Seminars in cancer biology.

[4]  Tiantong Zhu,et al.  Systematic Analysis of the Expression Profile and Prognostic Significance of the IGF2BP Family in Lung Adenocarcinoma. , 2022, Current cancer drug targets.

[5]  Adam L. Maclean,et al.  Age-dependent effects of Igf2bp2 on gene regulation, function, and aging of hematopoietic stem cells in mice. , 2022, Blood.

[6]  Xiang-Yu Li,et al.  LncRNA metastasis‐associated lung adenocarcinoma transcript‐1 promotes osteogenic differentiation of bone marrow stem cells and inhibits osteoclastic differentiation of Mø in osteoporosis via the miR‐124‐3p/IGF2BP1/Wnt/β‐catenin axis , 2021, Journal of tissue engineering and regenerative medicine.

[7]  A. Schlundt,et al.  Structures and target RNA preferences of the RNA-binding protein family of IGF2BPs: An overview. , 2021, Structure.

[8]  Francesca Frontini,et al.  The role of microRNAs in the osteogenic and chondrogenic differentiation of mesenchymal stem cells and bone pathologies , 2021, Theranostics.

[9]  J. Avruch,et al.  RNA m6A reader IMP2/IGF2BP2 promotes pancreatic β-cell proliferation and insulin secretion by enhancing PDX1 expression , 2021, Molecular metabolism.

[10]  Cuiping Yang,et al.  The role of m6A modification in the biological functions and diseases , 2021, Signal Transduction and Targeted Therapy.

[11]  Jinyan Wang,et al.  The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers , 2021, Cancer cell international.

[12]  S. Davaran,et al.  Osteogenic potential of the growth factors and bioactive molecules in bone regeneration. , 2021, International journal of biological macromolecules.

[13]  Da Liu,et al.  Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration , 2021, Stem cell research & therapy.

[14]  Jun Luo,et al.  Kaempferol promotes BMSC osteogenic differentiation and improves osteoporosis by downregulating miR-10a-3p and upregulating CXCL12 , 2020, Molecular and Cellular Endocrinology.

[15]  J. Valcárcel,et al.  RNA-binding proteins in human genetic disease , 2020, Nature reviews. Genetics.

[16]  T. Komori.  Functions of Osteocalcin in Bone, Pancreas, Testis, and Muscle , 2020, International journal of molecular sciences.

[17]  Jianhong Gu,et al.  Cadmium exposure triggers osteoporosis in duck via P2X7/PI3K/AKT-mediated osteoblast and osteoclast differentiation. , 2020, The Science of the total environment.

[18]  Fedor V. Karginov,et al.  Global Approaches in Studying RNA-Binding Protein Interaction Networks. , 2020, Trends in biochemical sciences.

[19]  Ning Dai.  The Diverse Functions of IMP2/IGF2BP2 in Metabolism , 2020, Trends in Endocrinology & Metabolism.

[20]  Margaret H. Frank,et al.  TBtools - an integrative toolkit developed for interactive analyses of big biological data. , 2020, Molecular plant.

[21]  D. Heckl,et al.  RNA-Binding Proteins in Acute Leukemias , 2020, International journal of molecular sciences.

[22]  W. Xie,et al.  m6A-binding proteins: the emerging crucial performers in epigenetics , 2020, Journal of Hematology & Oncology.

[23]  Alexa B. R. McIntyre,et al.  Limits in the detection of m6A changes using MeRIP/m6A-seq , 2019, Scientific Reports.

[24]  Qiong Xu,et al.  METTL3 Regulates Osteoblast Differentiation and Inflammatory Response via Smad Signaling and MAPK Signaling , 2019, International journal of molecular sciences.

[25]  Gang Yin,et al.  Functions of N6-methyladenosine and its role in cancer , 2019, Molecular Cancer.

[26]  Samie R Jaffrey,et al.  Reading, writing and erasing mRNA methylation , 2019, Nature Reviews Molecular Cell Biology.

[27]  Aleksandra A. Kolodziejczyk,et al.  The cell cycle in stem cell proliferation, pluripotency and differentiation , 2019, Nature Cell Biology.

[28]  J. Avruch,et al.  Liver-specific deletion of IGF2 mRNA binding protein-2/IMP2 reduces hepatic fatty acid oxidation and increases hepatic triglyceride accumulation , 2019, The Journal of Biological Chemistry.

[29]  R. Singer,et al.  The structural basis for RNA selectivity by the IMP family of RNA-binding proteins , 2019, Nature Communications.

[30]  P. Blackshear,et al.  Inhibiting transcription in cultured metazoan cells with actinomycin D to monitor mRNA turnover. , 2019, Methods.

[31]  Duanjing Chen,et al.  Bidirectional regulation of osteogenic differentiation by the FOXO subfamily of Forkhead transcription factors in mammalian MSCs , 2018, Cell proliferation.

[32]  D. Altshuler,et al.  IGF2BP2/IMP2-Deficient mice resist obesity through enhanced translation of Ucp1 mRNA and Other mRNAs encoding mitochondrial proteins. , 2015, Cell metabolism.

[33]  Yufei Huang,et al.  A protocol for RNA methylation differential analysis with MeRIP-Seq data and exomePeak R/Bioconductor package. , 2014, Methods.

[34]  Hui-Ann Wu,et al.  Serum response factor regulates bone formation via IGF‐1 and Runx2 signals , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[35]  B. Edgar,et al.  Mechanisms controlling cell cycle exit upon terminal differentiation. , 2007, Current opinion in cell biology.

[36]  P. Hughes,et al.  Cell differentiation and proliferation--simultaneous but independent? , 2003, Experimental cell research.

[37]  A. Skoultchi,et al.  Coordinating cell proliferation and differentiation. , 2001, Current opinion in genetics & development.

[38]  C. Tzen,et al.  Integrated control of proliferation and differentiation of mesenchymal stem cells. , 1989, Environmental health perspectives.