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image of Functional Analysis of miR-148a: A Differentially Expressed microRNA in Hemifacial Microsomia

Abstract

Introduction

Hemifacial Microsomia (HFM) is the second most common congenital deformity, yet its etiology and pathogenesis remain unclear. Therefore, this study aimed to identify differentially expressed microRNAs (miRNAs) between healthy and affected bone marrow mesenchymal stem cells (BMSCs) from HFM patients, focusing on the functional roles of miR-148a in osteogenesis and osteoclastogenesis.

Methods

The specific expression of microRNAs was screened by sequencing and verified by PCR. Through the use of mimics, inhibitors, and knockout technology, we controlled the expression of miR-148a and Osteogenesis and osteoclastogenesis induction, PCR, western blot, ALP staining, alizarin red staining, TRAP staining, micro-CT, and tissue sections were performed to explore the effects of miR-148 on osteogenesis and osteoclastogenesis.

Results

MiR-148a was identified and confirmed through our research as a differentially expressed miRNA in HFM. Overexpression of miR-148a increased osteogenesis-related gene and protein expression and mineralized calcium nodule formation while decreasing osteoclast-related gene and protein levels. Silencing or knockout of miR-148a produced opposite effects. miR-148a knockout mice were smaller than wild-type, with reduced osteogenesis, fewer trabeculae, increased trabecular bone separation in the mandible, and decreased ramus length. Additionally, local overexpression of miR-148a in knockout mice increased local bone mass.

Discussions

The current study findings demonstrate that miR-148a can influence the bone volume, and its role in chondrogenesis deserves further research. Additionally, further studies on the changes upstream of miR-148a that lead to differences in miR-148a expression between the healthy and affected sides of HFM patients and the differences in bone size are warranted to better understand HFM pathogenesis.

Conclusion

Our findings suggest that the opposing effects of miR-148a on osteogenesis and osteoclastogenesis lead to decreased bone mass in HFM. Local overexpression can reverse bone defects caused by miR-148a, suggesting its promising role in future treatments. We anticipate that further investigations will enhance our understanding and ultimately pave the way for the application of these insights in clinical settings for disease treatment.

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2025-07-23
2025-11-01

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References

  1. Mishra L. Misra S.R. Kumar M. Tripathy R. Hemifacial microsomia: A series of three case reports. J. Clin. Diagn. Res. 2013 7 10 2383 2386 10.7860/JCDR/2013/5773.3532 24298537
    [Google Scholar]
  2. Jangra B. Bhushan U. Jangra B. Goldenhar syndrome: A case report with review. Int. J. Clin. Pediatr. Dent. 2016 9 3 278 280 10.5005/jp‑journals‑10005‑1377 27843263
    [Google Scholar]
  3. Luo S. Sun H. Bian Q. Liu Z. Wang X. The etiology, clinical features, and treatment options of hemifacial microsomia. Oral Dis. 2023 29 6 2449 2462 10.1111/odi.14508 36648381
    [Google Scholar]
  4. Murray J.E. Kaban L.B. Mulliken J.B. Analysis and treatment of hemifacial microsomia. Plast. Reconstr. Surg. 1984 74 2 186 199 10.1097/00006534‑198408000‑00003 6463144
    [Google Scholar]
  5. Chen Q. Zhao Y. Shen G. Dai J. Etiology and Pathogenesis of Hemifacial Microsomia. J. Dent. Res. 2018 97 12 1297 1305 10.1177/0022034518795609 30205013
    [Google Scholar]
  6. Ongkosuwito E.M. van Vooren J. van Neck J.W. Changes of mandibular ramal height, during growth in unilateral hemifacial microsomia patients and unaffected controls. J. Craniomaxillofac. Surg. 2013 41 2 92 97 10.1016/j.jcms.2012.05.006 22789870
    [Google Scholar]
  7. Taiwo A.O. Classification and management of hemifacial microsomia: A literature review. Ann. Ib. Postgrad. Med. 2020 18 1 S9 S15 [PMID: 33071690
    [Google Scholar]
  8. Beleza-Meireles A. Clayton-Smith J. Saraiva J.M. Tassabehji M. Oculo-auriculo-vertebral spectrum: A review of the literature and genetic update. J. Med. Genet. 2014 51 10 635 645 10.1136/jmedgenet‑2014‑102476 25118188
    [Google Scholar]
  9. Shibazaki-Yorozuya R. Yamada A. Nagata S. Ueda K. Miller A.J. Maki K. Three-dimensional longitudinal changes in craniofacial growth in untreated hemifacial microsomia patients with cone-beam computed tomography. Am. J. Orthod. Dentofacial Orthop. 2014 145 5 579 594 10.1016/j.ajodo.2013.09.015 24785922
    [Google Scholar]
  10. Choi J. Park S.W. Kwon G.Y. Influence of congenital facial nerve palsy on craniofacial growth in craniofacial microsomia. J. Plast. Reconstr. Aesthet. Surg. 2014 67 11 1488 1495 10.1016/j.bjps.2014.07.020 25210001
    [Google Scholar]
  11. Yin M. Feng C. Yu Z. sc2GWAS: A comprehensive platform linking single cell and GWAS traits of human. Nucleic Acids Res. 2025 53 D1 D1151 D1161 10.1093/nar/gkae1008 39565208
    [Google Scholar]
  12. Nagy K. Kuijpers-Jagtman A.M. Mommaerts M.Y. No evidence for long-term effectiveness of early osteodistraction in hemifacial microsomia. Plast. Reconstr. Surg. 2009 124 6 2061 2071 10.1097/PRS.0b013e3181bcf2a4 19952663
    [Google Scholar]
  13. Yang I.H. Chung J.H. Yim S. Treatment modalities for Korean patients with unilateral hemifacial microsomia according to Pruzansky–Kaban types and growth stages. Korean J. Orthod. 2020 50 5 336 345 10.4041/kjod.2020.50.5.336 32938826
    [Google Scholar]
  14. Fariña R. Valladares S. Torrealba R. Nuñez M. Uribe F. Orthognathic surgery in craniofacial microsomia: Treatment algorithm. Plast. Reconstr. Surg. Glob. Open 2015 3 1 e294 10.1097/GOX.0000000000000259 25674375
    [Google Scholar]
  15. Chow A. Lee H.F. Trahar M. Kawamoto H. Vastardis H. Ting K. Cephalometric evaluation of the craniofacial complex in patients treated with an intraoral distraction osteogenesis device: A long-term study. Am. J. Orthod. Dentofacial Orthop. 2008 134 6 724 731 10.1016/j.ajodo.2007.01.029 19061798
    [Google Scholar]
  16. Song W. Shi Y. Lin G.N. Haplotype function score improves biological interpretation and cross-ancestry polygenic prediction of human complex traits. eLife 2024 12 RP92574 10.7554/eLife.92574.3 38639992
    [Google Scholar]
  17. Sun Y. Zong C. Liu J. C-myc promotes miR-92a-2-5p transcription in rat ovarian granulosa cells after cadmium exposure. Toxicol. Appl. Pharmacol. 2021 421 115536 10.1016/j.taap.2021.115536 33865896
    [Google Scholar]
  18. Ghani MU Ali S Imran M Karamti H Sultan F Almusawa MY Hex-derived molecular descriptors via generalized valency-based entropies. IEEE Access 2023 11 42052 68 10.1109/ACCESS.2023.3248507
    [Google Scholar]
  19. Khan A.R. Awan N.H. Ghani M.U. Fundamental aspects of skin cancer drugs via degree-based chemical bonding topological descriptors. Molecules 2023 28 9 3684 10.3390/molecules28093684 37175093
    [Google Scholar]
  20. Xavier D.A. Ghani M.U. Imran M. Nair A.T. Varghese E.S. Baby A. Comparative study of molecular descriptors of pent-heptagonal nanostructures using neighborhood M-polynomial approach. Molecules 2023 28 6 2518 10.3390/molecules28062518 36985488
    [Google Scholar]
  21. Ghani M.U. Campena F.J.H. Pattabiraman K. Ismail R. Karamti H. Husin M.N. Valency-based indices for some succinct drugs by using M-polynomial. Symmetry 2023 15 3 603 10.3390/sym15030603
    [Google Scholar]
  22. Ghani M.U. Imran M. Sampathkumar S. Tchier F. Pattabiraman K. Jan A.Z. A paradigmatic approach to the molecular descriptor computation for some antiviral drugs. Heliyon 2023 9 11 e21401 10.1016/j.heliyon.2023.e21401 38027690
    [Google Scholar]
  23. Ghani M.U. Inc M. Sultan F. Cancan M. Houwe A. Computation of Zagreb polynomial and indices for silicate network and silicate chain network. J. Math. 2023 2023 9722878 10.1155/2023/9722878
    [Google Scholar]
  24. Tingaud-Sequeira A. Trimouille A. Sagardoy T. Lacombe D. Rooryck C. Oculo-auriculo-vertebral spectrum: New genes and literature review on a complex disease. J. Med. Genet. 2022 59 5 417 427 10.1136/jmedgenet‑2021‑108219 35110414
    [Google Scholar]
  25. Song W. Xia X. Fan Y. Zhang B. Chen X. Functional and genetic analyses unveil the implication of CDC27 in Hemifacial Microsomia. Int. J. Mol. Sci. 2024 25 9 4707 10.3390/ijms25094707 38731925
    [Google Scholar]
  26. Zhang Y.B. Hu J. Zhang J. Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia. Nat. Commun. 2016 7 1 10605 10.1038/ncomms10605 26853712
    [Google Scholar]
  27. Wang X. Chai Y. Zhang Y. Chai G. Xu H. Exploration of novel genetic evidence and clinical significance into hemifacial microsomia pathogenesis. J. Craniofac. Surg. 2023 34 2 834 838 10.1097/SCS.0000000000009167 36745106
    [Google Scholar]
  28. Yoon A. Pham B. Dipple K. Genetic screening in patients with craniofacial malformations. J. Pediatr. Genet. 2016 5 4 220 224 10.1055/s‑0036‑1592423 27895974
    [Google Scholar]
  29. Zhao S. Sun P. Li X. Identification of Hub genes in hemifacial microsomia: Evidence from bioinformatic analysis. J. Craniofac. Surg. 2022 33 2 e145 e149 10.1097/SCS.0000000000008164 34855631
    [Google Scholar]
  30. Timberlake A.T. Griffin C. Heike C.L. Haploinsufficiency of SF3B2 causes craniofacial microsomia. Nat. Commun. 2021 12 1 4680 10.1038/s41467‑021‑24852‑9 34344887
    [Google Scholar]
  31. Yamaguchi T.P. Bradley A. McMahon A.P. Jones S.A. Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 1999 126 6 1211 1223 10.1242/dev.126.6.1211 10021340
    [Google Scholar]
  32. Minoux M. Kratochwil C.F. Ducret S. Mouse Hoxa2 mutations provide a model for microtia and auricle duplication. Development 2013 140 21 4386 4397 10.1242/dev.098046 24067355
    [Google Scholar]
  33. Gartel A.L. Kandel E.S. miRNAs: Little known mediators of oncogenesis. Semin. Cancer Biol. 2008 18 2 103 110 10.1016/j.semcancer.2008.01.008 18295504
    [Google Scholar]
  34. Saliminejad K. Khorram Khorshid H.R. Soleymani Fard S. Ghaffari S.H. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J. Cell. Physiol. 2019 234 5 5451 5465 10.1002/jcp.27486 30471116
    [Google Scholar]
  35. Ma Y. Zhang P. Yang J. Liu Z. Yang Z. Qin H. Candidate microRNA biomarkers in human colorectal cancer: Systematic review profiling studies and experimental validation. Int. J. Cancer 2012 130 9 2077 2087 10.1002/ijc.26232 21671476
    [Google Scholar]
  36. Diener C. Keller A. Meese E. Emerging concepts of miRNA therapeutics: From cells to clinic. Trends Genet. 2022 38 6 613 626 10.1016/j.tig.2022.02.006 35303998
    [Google Scholar]
  37. Mishra S. Yadav T. Rani V. Exploring miRNA based approaches in cancer diagnostics and therapeutics. Crit. Rev. Oncol. Hematol. 2016 98 12 23 10.1016/j.critrevonc.2015.10.003 26481951
    [Google Scholar]
  38. Lu T.X. Rothenberg M.E. MicroRNA. J. Allergy Clin. Immunol. 2018 141 4 1202 1207 10.1016/j.jaci.2017.08.034 29074454
    [Google Scholar]
  39. Ho P.T.B. Clark I.M. Le L.T.T. MicroRNA-Based diagnosis and therapy. Int. J. Mol. Sci. 2022 23 13 7167 10.3390/ijms23137167 35806173
    [Google Scholar]
  40. Bernardo B.C. Ooi J.Y.Y. Lin R.C.Y. McMullen J.R. miRNA therapeutics: A new class of drugs with potential therapeutic applications in the heart. Future Med. Chem. 2015 7 13 1771 1792 10.4155/fmc.15.107 26399457
    [Google Scholar]
  41. Zhou Y. Li Q. Pan R. Regulatory roles of three miRNAs on allergen mRNA expression in Tyrophagus putrescentiae. Allergy 2022 77 2 469 482 10.1111/all.15111 34570913
    [Google Scholar]
  42. Krol J. Loedige I. Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat. Rev. Genet. 2010 11 9 597 610 10.1038/nrg2843 20661255
    [Google Scholar]
  43. Tsai H.L. Yang I.P. Huang C.W. Clinical significance of microRNA-148a in patients with early relapse of stage II stage and III colorectal cancer after curative resection. Transl. Res. 2013 162 4 258 268 10.1016/j.trsl.2013.07.009 23933284
    [Google Scholar]
  44. Rupaimoole R. Slack F.J. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov. 2017 16 3 203 222 10.1038/nrd.2016.246 28209991
    [Google Scholar]
  45. Xu P. Li X. Liang Y. PmiRtarbase: A positive miRNA-target regulations database. Comput. Biol. Chem. 2022 98 107690 10.1016/j.compbiolchem.2022.107690 35567946
    [Google Scholar]
  46. Hill M. Tran N. miRNA:miRNA interactions: A novel mode of miRNA regulation and its effect on disease. Adv. Exp. Med. Biol. 2022 1385 241 257 10.1007/978‑3‑031‑08356‑3_9 36352217
    [Google Scholar]
  47. Tiwari A. Mukherjee B. Dixit M. MicroRNA key to angiogenesis regulation: MiRNA biology and therapy. Curr. Cancer Drug Targets 2018 18 3 266 277 10.2174/1568009617666170630142725 28669338
    [Google Scholar]
  48. miRNAs in Bone Formation and Homeostasis 2015 Available from: https://scholarship.miami.edu/esploro/outputs/bookChapter/Chapter-14---miRNAs-in-Bone/991031718436902976
  49. Jenzer A.C. Singh P. Anesthetic Considerations in Hemifacial Microsomia. Treasure Island, FL StatPearls Publihing 2025
    [Google Scholar]
  50. Pan B. Zheng L. Liu S. MiR-148a deletion protects from bone loss in physiological and estrogen-deficient mice by targeting NRP1. Cell Death Discov. 2022 8 1 470 10.1038/s41420‑022‑01261‑5 36446758
    [Google Scholar]
  51. Scian M.J. Maluf D.G. David K.G. MicroRNA profiles in allograft tissues and paired urines associate with chronic allograft dysfunction with IF/TA. Am. J. Transplant. 2011 11 10 2110 2122 10.1111/j.1600‑6143.2011.03666.x 21794090
    [Google Scholar]
  52. Scherer A. Krause A. Walker J.R. Korn A. Niese D. Raulf F. Early prognosis of the development of renal chronic allograft rejection by gene expression profiling of human protocol biopsies. Transplantation 2003 75 8 1323 1330 10.1097/01.TP.0000068481.98801.10 12717224
    [Google Scholar]
  53. Tian S. Zhou X. Zhang M. Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages. Stem Cell Res. Ther. 2022 13 1 330 10.1186/s13287‑022‑03010‑y 35858897
    [Google Scholar]
  54. Pan W. Zhu S. Yuan M. Cui H. Wang L. Luo X. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J. Immunol. 2010 184 6773 6781 10.4049/jimmunol.0904060
    [Google Scholar]
  55. Haftmann C. Stittrich A.B. Zimmermann J. miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim. Eur. J. Immunol. 2015 45 4 1192 1205 10.1002/eji.201444633 25486906
    [Google Scholar]
  56. Cao H. Liu Z. Wang R. miR-148a suppresses human renal cell carcinoma malignancy by targeting AKT2. Oncol. Rep. 2017 37 1 147 154 10.3892/or.2016.5257 27878305
    [Google Scholar]
  57. Zhang H. Li Y. Huang Q. MiR-148a promotes apoptosis by targeting Bcl-2 in colorectal cancer. Cell Death Differ. 2011 18 11 1702 1710 10.1038/cdd.2011.28 21455217
    [Google Scholar]
  58. Li Y. Deng X. Zeng X. Peng X. The role of Mir-148a in cancer. J. Cancer 2016 7 10 1233 1241 10.7150/jca.14616 27390598
    [Google Scholar]
  59. Xu C. Zhou G. Sun Z. Zhang Z. Zhao H. Jiang X. miR-148a-3p inhibits the proliferation and migration of bladder cancer via regulating the expression of ROCK-1. PeerJ 2022 10 e12724 10.7717/peerj.12724 35127282
    [Google Scholar]
  60. Xia J. Guo X. Yan J. Deng K. The role of miR-148a in gastric cancer. J. Cancer Res. Clin. Oncol. 2014 140 9 1451 1456 10.1007/s00432‑014‑1649‑8 24659367
    [Google Scholar]
  61. Kelch S. Balmayor E.R. Seeliger C. Vester H. Kirschke J.S. van Griensven M. miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci. Rep. 2017 7 1 15861 10.1038/s41598‑017‑16113‑x 29158518
    [Google Scholar]
  62. Liu H. Su H. Wang X. Hao W. MiR-148a regulates bone marrow mesenchymal stem cells-mediated fracture healing by targeting insulin-like growth factor 1. J. Cell. Biochem. 2019 120 2 1350 1361 10.1002/jcb.27121 30335895
    [Google Scholar]
  63. Bedene A Mencej Bedrač S Ješe L MiR-148a the epigenetic regulator of bone homeostasis is increased in plasma of osteoporotic postmenopausal women. Wien Klin Wochenschr 2016 128 (S7) 519 26 (Suppl. 7) 10.1007/s00508‑016‑1141‑3 27900532
    [Google Scholar]
  64. Grieco G.E. Cataldo D. Ceccarelli E. Serum levels of miR-148a and miR-21-5p are increased in type 1 diabetic patients and correlated with markers of bone strength and metabolism. Noncoding RNA 2018 4 4 37 10.3390/ncrna4040037 30486455
    [Google Scholar]
  65. Liu N. Sun Y. microRNA-148a-3p-targeting p300 protects against osteoblast differentiation and osteoporotic bone reconstruction. Regen. Med. 2021 16 5 435 449 10.2217/rme‑2020‑0006 34000812
    [Google Scholar]
  66. Lin Y. Li H. Zheng S. Elucidating tobacco smoke-induced craniofacial deformities: Biomarker and MAPK signaling dysregulation unraveled by cross-species multi-omics analysis. Ecotoxicol. Environ. Saf. 2024 288 117343 10.1016/j.ecoenv.2024.117343 39549573
    [Google Scholar]
  67. Bao M.H. Li G.Y. Huang X.S. Tang L. Dong L.P. Li J.M. Long noncoding RNA LINC00657 acting as a miR-590-3p Sponge to facilitate low concentration oxidized low-density lipoprotein-induced angiogenesis. Mol. Pharmacol. 2018 93 4 368 375 10.1124/mol.117.110650 29436491
    [Google Scholar]
  68. Zhang H. Wang Y. Xu T. Increased expression of microRNA-148a in osteosarcoma promotes cancer cell growth by targeting PTEN. Oncol. Lett. 2016 12 5 3208 3214 10.3892/ol.2016.5050 27899984
    [Google Scholar]
  69. Pan J.M. Wu L.G. Cai J.W. Wu L.T. Liang M. Dexamethasone suppresses osteogenesis of osteoblast via the PI3K/Akt signaling pathway in vitro and in vivo. J. Recept. Signal Transduct. Res. 2019 39 1 80 86 10.1080/10799893.2019.1625061 31210570
    [Google Scholar]
  70. Furue K. Sena K. Sakoda K. Nakamura T. Noguchi K. Involvement of the phosphoinositide 3-kinase/Akt signaling pathway in bone morphogenetic protein 9-stimulated osteogenic differentiation and stromal cell-derived factor 1 production in human periodontal ligament fibroblasts. Eur. J. Oral Sci. 2017 125 2 119 126 10.1111/eos.12336 28191670
    [Google Scholar]
  71. Ou J. Li N. He H. He J. Zhang L. Jiang N. Detecting muscle fatigue among community-dwelling senior adults with shape features of the probability density function of sEMG. J. Neuroeng. Rehabil. 2024 21 1 196 10.1186/s12984‑024‑01497‑5 39497122
    [Google Scholar]
  72. Li N. Ou J. He H. Exploration of a machine learning approach for diagnosing sarcopenia among Chinese community-dwelling older adults using sEMG-based data. J. Neuroeng. Rehabil. 2024 21 1 69 10.1186/s12984‑024‑01369‑y 38725065
    [Google Scholar]
  73. Huh J. Park J.S. Sodnom-Ish B. Yang H.J. Growth characteristics and classification systems of hemifacial microsomia: A literature review. Maxillofac. Plast. Reconstr. Surg. 2024 46 1 18 10.1186/s40902‑024‑00427‑8 38733452
    [Google Scholar]
  74. AlZamel G. Odell S. Mupparapu M. Developmental disorders affecting jaws. Dent. Clin. North Am. 2016 60 1 39 90 10.1016/j.cden.2015.08.002 26614949
    [Google Scholar]
  75. Kawamoto H.K. Kim S.S. Jarrahy R. Bradley J.P. Differential diagnosis of the idiopathic laterally deviated mandible. Plast. Reconstr. Surg. 2009 124 5 1599 1609 10.1097/PRS.0b013e3181babc1f 20009847
    [Google Scholar]
  76. Pirttiniemi P. Peltomäki T. Müller L. Luder H.U. Abnormal mandibular growth and the condylar cartilage. Eur. J. Orthod. 2009 31 1 1 11 10.1093/ejo/cjn117 19164410
    [Google Scholar]
  77. Kim B.C. Bertin H. Kim H.J. Structural comparison of hemifacial microsomia mandible in different age groups by three-dimensional skeletal unit analysis. J. Craniomaxillofac. Surg. 2018 46 11 1875 1882 10.1016/j.jcms.2018.08.009 30244962
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240371562250710210716
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Functional Analysis of miR-148a: A Differentially Expressed microRNA in Hemifacial Microsomia
Bentham Science Publishers ; https://doi.org/10.2174/0115665240371562250710210716
/content/journals/cmm/10.2174/0115665240371562250710210716
/content/journals/cmm/10.2174/0115665240371562250710210716
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  • Article Type:     Research Article
Keywords: hemifacial microsomia ; bone marrow mesenchymal stem cell ; osteoclastogenesis ; osteogenesis ; Functional analysis ; microRNA miR-148a

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