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Aberrant expression of microRNA-99a and its target gene mTOR associated with malignant progression and poor prognosis in patients with osteosarcoma

Authors Zhao J, Chen F, Zhou Q, Pan W, Wang X, Xu J, Ni L, Yang H

Received 13 December 2015

Accepted for publication 14 February 2016

Published 17 March 2016 Volume 2016:9 Pages 1589—1597


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Professor Min Li

Jiali Zhao,1,2,* Fengli Chen,3,* Quan Zhou,2 Wei Pan,2 Xinhong Wang,2 Jin Xu,2 Li Ni,1 Huilin Yang1

1Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 2Department of Orthopedics, The Affiliated Huai’an Hospital of Xuzhou Medical College and The Second People’s Hospital of Huai’an, Huai’an, 3Central Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

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. 
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 clinicopathological 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. 
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.

microRNA-99a, mammalian target of rapamycin, osteosarcoma, quantitative real-time PCR, prognosis

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