Des pite this, approximately 30% of patients relapse or develop metastasis. The lack of responsiveness to chemotherapy due to intrinsic or acquired chemoresis tance is the major reason for poor survival and disease relapse of OS patients. Recently, novel molecular tar geted drugs have emerged, but they have not been well established for the treatment of OS. In addition, the molecular mechanisms underlying OS chemoresistance remain largely obscure. Hence, identification of factors that contribute to OS chemoresistance and elucidation of the underlying mechanisms will be pivotal in the de velopment of new therapeutic strategies. TWIST, also known as TWIST1, belongs to the basic helix loop helix transcription factor family.

Dur ing embryonic development, TWIST plays an essential role in specification of the mesoderm and differentiation of the mesoderm derived tissues. Twist haploinsuffi ciency was shown to upset bone tissue in both mice and humans. In homogeneous inhibitor cohort of OS patients, the TWIST gene was frequently deleted in the tumors at diagnosis, and its haploinsufficiency was significantly correlated with a poorer patient outcome. It has been reported that TWIST decreases OS cell survival against cisplatin by inhibiting B catenin signaling and endothelin 1 endothelin A receptor signaling pathways, suggesting that TWIST is an important negative regulator in the development of OS chemoresistance. MicroRNAs are noncoding small RNAs, usually 18 25 nucleotides in length, which repress translation and cleave mRNA by base pairing to the 3 untranslated region of the target genes.

Knowledge of individual miRNAs effecting develop mental biology, cellular BAPTA-AM VEGFR inhibitor differentiation programs, and oncogenesis continues to grow. Differences in the miRNA expression profiles detected between cancer cells and their normal counterparts have revealed that miRNAs are involved in the pathogenesis of cancer. In addition, miRNAs may play multiple roles as tumor suppressors, oncogenes, or both in some cases. The biological properties of miRNAs may make them useful as diagnostic and prognostic tools as well as therapeutic targets in various cancers, including OS. A number of miRNAs reportedly are involved in OS tumorigenesis and chemoresistance. In the present study, we screened for miRNAs regulat ing TWIST expression in human OS and explored their functional interaction in modulating human OS chemoresistance. Methods Patients From November 2010 to May 2013, we enrolled two co horts of OS patients. The discovery cohort consists of six Han Chinese OS patients who showed 90% tumor necrosis after chemotherapy and were defined as poor responders at the third Xiangya Hospital of Central South University.