The miR‐143/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin‐1

作者: Joaquin Urdinez , Aleksandar Boro , Alekhya Mazumdar , Matthias JE Arlt , Roman Muff

DOI: 10.1002/JBMR.3976

关键词: ChondrosarcomaDownregulation and upregulationBone cancerCancer researchmicroRNABiomarker (cell)MedicineBone SarcomaFascinIn silico

摘要: Chondrosarcoma is the second most frequent bone sarcoma. Due to inherent chemotherapy and radiotherapy resistance absence of known therapeutic targets, clinical management limited surgical resection. Consequently, patients with advanced disease face a poor prognosis. Hence, elucidating regulatory networks governing chondrosarcoma pathogenesis vital for development effective strategies. Here, miRNA mRNA next generation sequencing different subtypes human chondrogenic tumors in combination silico bioinformatics tools were performed aim identify key molecular factors. We identified miR-143/145 cluster levels inversely correlate tumor grade. This deregulation was echoed plasma we provided first evidence that circulating miR-145 potential noninvasive diagnostic biomarker can be valuable as an indicator improve currently challenging diagnosis cartilaginous tumors. Additionally, artificial upregulation both miRNAs impelled potent suppressor effect vitro vivo orthotopic xenograft mouse model. A combined silico/sequencing approach revealed FSCN1 direct target miR-143/145, its depletion phenotypically resembled vitro. Last, malignancy-promoting factor associated aggressive progression. Our findings underscore miR-143/145/FSCN1 important players may potentially open new avenues specific intervention options. © 2020 American Society Bone Mineral Research.

参考文章(63)
Christopher D.M. Fletcher, Krisjnan Unni, Fredrik Mertens, World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone IARC Press. ,(2002)
Karimollah Hajian-Tilaki, Receiver Operating Characteristic (ROC) Curve Analysis for Medical Diagnostic Test Evaluation caspian journal of internal medicine. ,vol. 4, pp. 627- 635 ,(2013)
Teruhito Yoshitaka, Akira Kawai, Shigeru Miyaki, Kunihiko Numoto, Kazutaka Kikuta, Toshifumi Ozaki, Martin Lotz, Hiroshi Asahara, Analysis of microRNAs expressions in chondrosarcoma. Journal of Orthopaedic Research. ,vol. 31, pp. 1992- 1998 ,(2013) , 10.1002/JOR.22457
Özge Uluçkan, Aude Segaliny, Sander Botter, Janice M Santiago, Anthony J Mutsaers, Preclinical mouse models of osteosarcoma. bonekey Reports. ,vol. 4, pp. 670- 670 ,(2015) , 10.1038/BONEKEY.2015.37
Yafeng Ma, Laura M. Machesky, Fascin1 in carcinomas: Its regulation and prognostic value International Journal of Cancer. ,vol. 137, pp. 2534- 2544 ,(2015) , 10.1002/IJC.29260
Yosuke Hashimoto, Dae Joong Kim, Josephine C Adams, The roles of fascins in health and disease The Journal of Pathology. ,vol. 224, pp. 289- 300 ,(2011) , 10.1002/PATH.2894
Andrej Valkov, Sveinung W. Sorbye, Thomas K. Kilvaer, Tom Donnem, Eivind Smeland, Roy M. Bremnes, Lill-Tove Busund, The Prognostic Impact of TGF-β1, Fascin, NF-κB and PKC-ζ Expression in Soft Tissue Sarcomas PLoS ONE. ,vol. 6, pp. e17507- ,(2011) , 10.1371/JOURNAL.PONE.0017507
Yusuke Kanda, Tokuichi Kawaguchi, Yasuhiro Kuramitsu, Takao Kitagawa, Tokushige Kobayashi, Norihiko Takahashi, Hiroshi Tazawa, Hasem Habelhah, Jun-ichi Hamada, Masanobu Kobayashi, Mio Hirahata, Kunishige Onuma, Mitsuhiko Osaki, Kazuyuki Nakamura, Tomoyuki Kitagawa, Masuo Hosokawa, Futoshi Okada, Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis. Proteomics. ,vol. 14, pp. 1031- 1041 ,(2014) , 10.1002/PMIC.201300414
Josephine C Adams, Roles of fascin in cell adhesion and motility Current Opinion in Cell Biology. ,vol. 16, pp. 590- 596 ,(2004) , 10.1016/J.CEB.2004.07.009