title: Aberrant expression of microRNA-99a and its target gene mTOR associated with malignant progression and poor prognosis in patients with osteosarcoma.
abstract: BACKGROUND
  The mammalian target of rapamycin (mTOR) has been reported to act as a target gene of microRNA (miR)-99a in various cancer cells and identified as an independent prognostic marker of human osteosarcoma. The aim of this study was to investigate the clinical significance of miR-99a/mTOR axis in human osteosarcoma.
  
  
  METHODS
  A total of 130 pairs of osteosarcoma and matched noncancerous bone tissues were used to detect the expression levels of miR-99a and mTOR mRNA by quantitative real-time polymerase chain reaction. Then, associations of miR-99a and/or mTOR expression with clinico-pathological features and prognosis of patients with osteosarcoma were statistically analyzed.
  
  
  RESULTS
  The expression levels of miR-99a (tumor vs normal: 2.11±1.03 vs 4.69±1.21, P<0.001) and mTOR mRNA (tumor vs normal: 4.40±1.13 vs 1.74±0.85, P<0.001) in osteosarcoma tissues were, respectively, lower and higher than those in noncancerous bone tissues. The expression levels of miR-99a in osteosarcoma tissues were negatively correlated with those of mTOR mRNA. Additionally, miR-99a-low and/or mTOR-high expression were all significantly associated with advanced surgical stage, positive metastasis and recurrence, and poor response to chemotherapy (all P<0.05). Moreover, patients with osteosarcoma with miR-99a-low and/or mTOR-high expression had shorter overall and disease-free survivals than those in miR-99a-high and/or mTOR-low expression groups. Multivariate Cox analyses showed that miR-99a and/or mTOR expression were all independent prognostic factors of osteosarcoma.
  
  
  CONCLUSIONS
  Our data showed the crucial role of miR-99a/mTOR axis in the malignant progression of human osteosarcoma, implying that conjoined expression of miR-99a and mTOR may offer an attractive novel prognostic marker for this disease.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China; Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, People's Republic of China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Central Laboratory, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, People's Republic of China.
authors.forename: Fengli
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, People's Republic of China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, People's Republic of China.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
keywords: mammalian target of rapamycin; microRNA-99a; osteosarcoma; prognosis; quantitative real-time PCR