Abstract
Circular RNA (circRNA) is a key regulator in the development and progression of human cancers, however its role in osteosarcoma tumorigenesis is not well understood. The present study aims to investigate the expression profiles and potential modulation of circRNA on osteosarcoma carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in osteosarcoma tissue and circRNA-0008717 was identified as one circRNA significantly upregulated in osteosarcoma tissue. Osteosarcoma patients with high circRNA-0008717 expression had shortened survival. Gain and loss functional assays suggested that knockdown of circRNA-0008717 suppressed cell proliferation, migration and invasion, but promoted cell apoptosis. By using biotin-labeled circRNA-0008717 probe to perform RNA precipitation in osteosarcoma cells, we identified miR-203 as the circ0008717-associated microRNA. Subsequently, Bmi-1 was identified as the functional target of miR-203. In addition, overexpression of circRNA-0008717 in osteosarcoma could elevate Bmi-1 expression, resulting in the promotion of osteosarcoma cell proliferation and invasion. Furthermore, the tumor promoting effect of circRNA-0008717 was abolished by miR-203 mimics or Bmi-1 silencing vector. In conclusion, circRNA-0008717 plays an oncogenic role in osteosarcoma and may serve as a promising prognostic biomarker for osteosarcoma patients. Therefore, silence of circRNA-0008717 could be a future direction to develop a novel treatment strategy.
Highlights
Osteosarcoma is the most common primary bone malignancy in children and young adults, and accounts for approximately 60% of malignant bone tumors in the first two decades of life [1]
It is widely accepted that searching new therapeutic targets and better understanding the pathway related to cancer initiation and progression is essential for improving the prognosis of osteosarcoma patients
We focused on a novel gene regulator, circRNA, and validated the upregulation of circRNA-0008717 in osteosarcoma specimens
Summary
Osteosarcoma is the most common primary bone malignancy in children and young adults, and accounts for approximately 60% of malignant bone tumors in the first two decades of life [1]. Pulmonary metastasis is the most common cause for cancer-related death [2]. Despite advancement strategies such as surgery, adjuvant chemotherapy, and radiotherapy, the prognosis of osteosarcoma still remains poor, and the survival of osteosarcoma patients reached a plateau [3,4,5]. Circular RNAs (circRNAs) are a class of non-coding RNAs characterized by covalently closed continuous loops with neither 5′ to 3′ polarity nor a polyadenylated tail [8]. They have been found to play an important role in the regulation of multiple diseases, including cancer [9, 10]
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