title: Down-regulation of microRNA-26a and up-regulation of microRNA-27a contributes to aggressive progression of human osteosarcoma.
abstract: BACKGROUND
  Osteosarcoma is the most common primary bone malignancy with high local aggressiveness and rapid metastasizing potential, resulting in poor survival. Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression of miR-26a and miR-27a in osteosarcoma need further investigation in clinical samples. In our study, we evaluate the expression of these miRNAs in osteosarcoma tissues and compared with paired adjacent non-tumor bone tissues using RT-qPCR.
  
  
  METHODS
  Total RNA was purified from patients with osteosarcoma and noncancerous bone tissues. Real-time PCR was applied to quantify the expression level of miR-26a and miR-27a. Moreover, the correlation of these markers with clinicopathological characteristics was also evaluated in osteosarcoma patients. A cox proportional hazards model was performed to assess multivariate analyses of prognostic values.
  
  
  RESULTS
  Our result suggested that miR-26aexpression level in osteosarcoma bone tissue was significantly lower than that in the paired noncancerous bone tissues. MiR-27a expression was higher in osteosarcoma bone tissue in comparison with paired noncancerous bone tissues. The results indicated that low expression level of miR-26a and high expression of miR-27a were associated with high TNM stage (P = 0.001; P = 0.012), tumor grade (P = 0.007; P = 0.016), and distant metastasis (P = 0.004; P = 0.001). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-26a and high expression of miR-27a had shorter overall survival (log-rank test: P < 0.001). Multivariate Cox proportional hazards model analysis showed that low expression of miR-26a and high expression of miR-27a (P = 0.021; P = 0.011), high TNM stage (P = 0.001; P = 0.003), tumor grade (P = 0.005; P = 0.01), and distant metastasis.(P = 0.002; P = 0.005) were independent prognostic factors for overall survival patients with osteosarcoma cancer.
  
  
  CONCLUSIONS
  In conclusion, our findings suggested that expression level of miR-26a and miR-27a contributes to aggressive progression of this malignancy. Therefore, may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.
authors.affiliation: Department of Orthopedics Surgery, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Taheriazam
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Birjand University of Medical Sciences, Birjand, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Bahador
authors.affiliation: Department of Anesthesiology, Birjand University of Medical Sciences, Birjand, Iran.
authors.forename: Seyyed Hasan
authors.initials: SH
authors.lastname: Karbasy
authors.affiliation: Department of Orthopedics, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Seyed Mir Mansoor Moazen
authors.initials: SM
authors.lastname: Jamshidi
authors.affiliation: Department of Orthopedics, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Torkaman
authors.affiliation: Department of Molecular Biology, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Emad
authors.initials: E
authors.lastname: Yahaghi
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Birjand University of Medical Sciences, Birjand, Iran. mshakeri7@yahoo.com.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Shakeri
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D012516:Osteosarcoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C528163:MIRN26 microRNA, human; C531388:MIRN27 microRNA, human