Abstract
BackgroundClinical treatment of osteosarcoma suffers from high recurrence rate. Therefore, is of great clinical values to develop predictive markers for recurrent osteosarcoma. Cervical carcinoma high-expressed lncRNA 1 (lncRNA CCHE1) participates in several types of malignancies, while its functionality in osteosarcoma is unknown. This study was therefore carried out to explore the involvement of lncRNA CCHE1 in recurrent osteosarcoma.MethodsA total of 87 osteosarcoma patients received surgical resection and 38 healthy volunteers were included in this study. The 87 osteosarcoma patients were followed up for 5 years to record the recurrence of osteosarcoma. Plasma levels of lncRNA CCHE1 and ROCK1 on the day of discharge and during follow-up were measured by real-time quantitative PCR and ELISA, respectively. The effects of CCHE1 siRNA silencing on ROCK1 expression were analyzed by real-time quantitative PCR and western blot. Transwell assay was performed to analyze the role of lncRNA CCHE1 and ROCK1 in regulating cell invasion and migration.ResultsWe observed that, on the day of discharge, plasma lncRNA CCHE1 was upregulated in osteosarcoma patients who developed distant recurrence (DR) during follow-up than in osteosarcoma patients who developed local recurrence (LR), patients with non-recurrence (NR) and healthy controls. On the day of discharge, plasma levels of ROCK1 were higher in DR, LR and NR groups in comparison to healthy controls. On the day of discharge, plasma levels of lncRNA CCHE1 were positively correlated with plasma levels of ROCK1 only in patients who developed DR during follow-up, but not in patients who developed LR, NR and control groups. During follow-up, plasma levels of lncRNA CCHE1 were further increased in DR group but slightly decreased in LR and NR groups. LncRNA CCHE1 siRNA silencing inhibited, while ROCK1 overexpression promoted osteosarcoma cell invasion and migration. ROCK1 overexpression attenuated the role of CCHE1. LncRNA CCHE1 siRNA silencing led to inhibited ROCK1 expression in cancer cells.ConclusionTherefore, lncRNA CCHE1 may participate in postoperative distant recurrence of osteosarcoma caner possibly by interacting with ROCK1 to promote cancer cell invasion and migration.
Highlights
Clinical treatment of osteosarcoma suffers from high recurrence rate
In the present study we showed that Long non-coding RNA (lncRNA) CCHE1 could participate in postoperative distant recurrence of osteosarcoma possibly by interacting with Rho-associated protein kinase 1 (ROCK1)
Differential expression of plasma lncRNA CCHE1 in different groups QRT-PCR results revealed that, on the day of discharge, plasma lncRNA CCHE1 was upregulated in osteosarcoma patients who developed distant recurrence (DR) during follow-up than in osteosarcoma patients who developed local recurrence (LR), patients with NR and Plasma levels of lncRNA CCHE1 were positively correlated with plasma levels of ROCK1 only in DR group On the day of discharge, Pearson correlation coefficient analysis showed that plasma levels of lncRNA CCHE1 were positively correlated with plasma levels of ROCK1 in DR group (Fig. 3a)
Summary
Clinical treatment of osteosarcoma suffers from high recurrence rate. Is of great clinical values to develop predictive markers for recurrent osteosarcoma. With the development of early diagnosis programs and surgical resection techniques, treatment outcomes of cancer at early stages have been significantly improved [1, 2]. Postoperative survival of cancer patients is still challenged by the higher recurrence rate, which is a major cause of poor survival [3, 4]. Surgical resection can reach radical treatment in many cases of osteosarcoma patients, recurrence inevitably occur in a considerable portion of osteosarcoma patients, lead to poor survival [6]. How to further improve the treatment and prevent postoperative recurrence of osteosarcoma is still a focus of the clinical treatment of osteosarcoma
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