Abstract

Long non-coding RNAs (lncRNAs) have been shown to exert essential roles in development and progression of tumors. Here we discovered a novel lncRNA, RAB11B antisense RNA (RAB11B-AS1), which is markedly down-regulated in human osteosarcoma (OS) and associated with OS metastasis and poor prognosis. We find that reduction of RAB11B-AS1 significantly facilitates proliferation, migration and invasiveness and prevents apoptosis of OS cells and results in lower sensitivity to cisplatin in these cells. In contrast, up-regulation of RAB11B-AS1 suppresses the aggressive behaviors of OS cells. Mechanistically, down-regulation of RAB11B-AS1 elevates its sense-cognate gene RAB11B expression at both mRNA and protein levels. RAB11B-AS1 expression correlates negatively with RAB11B expression in OS tissues. Luciferase reporter assay illuminated that RAB11B-AS1 regulates RAB11B expression through antisense pairing. Most importantly, all the effects of RAB11B-AS1 were abrogated by RAB11B down-regulation. Thus our findings revealed that lnc-RAB11B-AS1 prevents osteosarcoma development and progression via inhibiting RAB11B expression, indicating lnc-RAB11B-AS1 as a potential therapeutic target for osteosarcoma.

Highlights

  • Osteosarcoma (OS), the most common primary bone sarcoma, is one of the malignant tumors threating teenagers’ life and health seriously [1, 2]

  • The majority of lncRAB11B-AS1 was shown to be localized in nucleus other than in cytoplasm of cells, suggesting the Long non-coding RNAs (lncRNAs) as a transcriptional regulator in osteosarcoma cells (Figure 1B)

  • Respectable researches have been executed on the antisense lncRNAs in different tumors

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Summary

Introduction

Osteosarcoma (OS), the most common primary bone sarcoma, is one of the malignant tumors threating teenagers’ life and health seriously [1, 2]. It is exigent to develop novel targets for the diagnosis, treatment and prognosis of osteosarcoma. LncRNA closely associates with the biological behavior of the tumor, including occurrence, development, invasion and metastasis of tumors [10,11,12]. Due to these characteristics, lncRNA has potential role in early diagnosis, treatment, and prognosis of tumors. LncRNA has potential role in early diagnosis, treatment, and prognosis of tumors When it comes to osteosarcoma, overexpression of lncRNA HOTTIP increases chemoresistance of osteosarcoma cell by activating the Wnt/β-catenin pathway [13]. Quite few investigations have been executed on the role of lncRNAs in osteosarcoma until recently, and the underlying mechanisms are largely unknown

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