Long Non-Coding RNA ANRIL as a Potential Biomarker of Chemosensitivity and Clinical Outcomes in Osteosarcoma

International Journal of Molecular Sciences

Adam M. Lee¹  R. Stephanie Huang¹  Daniel C. Kim¹  Aritro Nath²  Elise Moore³  Asmaa Ferdjallah⁴  Emily Greengard⁴ 

[1] Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA;Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center, Monrovia, CA 91007, USA;Department of Natural Sciences, Zanvyl Krieger School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA;Department of Pediatrics, Hematology & Oncology, University of Minnesota, Minneapolis, MN 55455, USA;

关键词: osteosarcoma;    cisplatin;    doxorubicin;    long non-coding RNA;    ANRIL;    CDKN2B-AS1;   

DOI  :  10.3390/ijms222011168

来源: DOAJ

【 摘 要 】

Osteosarcoma has a poor prognosis due to chemo-resistance and/or metastases. Increasing evidence shows that long non-coding RNAs (lncRNAs) can play an important role in drug sensitivity and cancer metastasis. Using osteosarcoma cell lines, we identified a positive correlation between the expression of a lncRNA and ANRIL, and resistance to two of the three standard-of-care agents for treating osteosarcoma—cisplatin and doxorubicin. To confirm the potential role of ANRIL in chemosensitivity, we independently inhibited and over-expressed ANRIL in osteosarcoma cell lines followed by treatment with either cisplatin or doxorubicin. Knocking-down ANRIL in SAOS2 resulted in a significant increase in cellular sensitivity to both cisplatin and doxorubicin, while the over-expression of ANRIL in both HOS and U2OS cells led to an increased resistance to both agents. To investigate the clinical significance of ANRIL in osteosarcoma, we assessed ANRIL expression in relation to clinical phenotypes using the osteosarcoma data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset. Higher ANRIL expression was significantly associated with increased rates of metastases at diagnosis and death and was a significant predictor of reduced overall survival rate. Collectively, our results suggest that the lncRNA ANRIL can be a chemosensitivity and prognosis biomarker in osteosarcoma. Furthermore, reducing ANRIL expression may be a therapeutic strategy to overcome current standard-of-care treatment resistance.

【 授权许可】

Unknown