title: Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma.
abstract: The sex-determining region Y-box 4 (SOX4), a transcription factor, is involved in various developmental processes. It has been reported in multiple human cancers. However, the prognostic value and its exact role in chondrosarcoma remain poorly understood. In the current study, SOX4 was overexpressed in 28 of 92 (30.4 %) interpretable chondrosarcoma patients compared with 3 of 43 (6.9 %) interpretable chondroma cases (P = 0.003). Its overexpression in chondrosarcoma was significantly associated with histological grade (P < 0.001) and the presence of tumor recurrence (P = 0.041). In addition, SOX4 overexpression was notably correlated with c-MYC (P = 0.011) and P53 (P = 0.029) expression as well as high Ki67 labeling index (LI) (P < 0.001) in our cohort. More importantly, we found that SOX4 was an unfavorable independent prognostic factor for chondrosarcoma patients with low histological grade. Functionally, SOX4 silencing significantly suppressed the proliferation, migratory, and invasive capacity of SW1353 cells, suggesting an oncogenic role of SOX4 in chondrosarcoma in vitro. In an attempt of characterizing SOX4 overexpression mechanism, we identified miR-30a as a tumor suppressor that directly targets SOX4 in chondrosarcoma cells. Clinically, miR-30a expression was negatively correlated with SOX4 expression in chondrosarcoma cases. In all, we identified that SOX4 was oncogenic in chondrosarcoma and negatively regulated by miR-30a in vitro. Importantly, SOX4 overexpression may serve as a prognostic marker for patients with low-histological-grade chondrosarcoma.
authors.affiliation: Department of Pathology, Shandong University Medical School, #44, Wenhua Xi Rd, Jinan, 250012, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Qi
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dong
authors.forename: Xiying
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhai
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Long
authors.initials: L
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Xiang
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D055751:SOXC Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors