Abstract
BackgroundAn increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in cancer onset and development. LncRNA AFAP1-AS1 has been validated to be abnormally upregulated and play oncogenic roles in various malignant tumors. The biological role and mechanism of AFAP1-AS1 in OS (osteosarcoma) remains unclear.MethodsQuantitative reverse transcription PCR (qRT-PCR) is applied to examine AFAP1-AS1 expression in OS tissues and OS cell lines. The function of AFAP1-AS1 in OS cells is investigated via in-vitro and in-vivo assays. Western bolt and rescue experiments are applied to detect the expression changes of key molecules including epithelial-mesenchymal transition markers and identify the underlying molecular mechanism. RNA immunoprecipitation is performed to reveal the interaction between AFAP1-AS1 and RhoC.ResultsAFAP1-AS1 expression is upregulated in human OS tissues and cell lines. AFAP1-AS1 knockdown induces OS cell apoptosis and cell cycle G0/G1 arrest, suppresses OS cells growth, migration, invasion, vasculogenic mimicry formation and epithelial-mesenchymal transition (EMT), and affects actin filament integrity. AFAP1-AS1 knockdown suppresses OS tumor formation and growth in nude mice. AFAP1-AS1 knockdown elicits a signaling inhibition including decreased levels of RhoC, ROCK1, p38MAPK and Twist1. Moreover, AFAP1-AS1 interacts with RhoC. Overexpression of RhoC can partly reverse AFAP1-AS1 downregulation-induced cell EMT inhibition.ConclusionsAFAP1-AS1 is overexpressed in osteosarcoma and plays an oncogenic role in osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway, in which RhoC acts as the interaction target of AFAP1-AS1. Our findings indicated a novel molecular mechanism underlying the tumorigenesis and progression of osteosarcoma. AFAP1-AS1 could serve as a promising therapeutic target in OS treatment.
Highlights
An increasing number of studies have demonstrated that long non-coding RNAs play pivotal roles in cancer onset and development
Expression of Actin filament-associated protein 1 (AFAP1)-AS1 is upregulated in human OS tissues and cell lines We firstly evaluated the transcript levels of AFAP1-AS1 in 8 cases of human OS tissues and their matched adjacent non-tumor tissues by Quantitative reverse transcription PCR (qRT-PCR)
These results indicated that AFAP1-AS1 might play a pivotal role in OS tumorigenesis and development
Summary
An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in cancer onset and development. The main treatment regimen for osteosarcoma is surgical resection combined with chemotherapy. According to recent research conclusions, osteosarcoma patients’ overall survival has been dramatically improved through widely used neoadjuvant and adjuvant chemotherapeutic regimens. For osteosarcoma patients without distant metastasis, the five-year survival rate can reach 55–70% after standardized treatment, in which around 90% of patients can attain limb salvage. For patients with early metastasis or chemo-resistance, even if treated with standard adjuvant chemotherapy and tumor resection, the five-year survival rate is approximately 5– 20% [4,5,6]. A better understanding of tumor biological behavior of osteosarcoma and deeper investigation of pivotal mechanism promoting osteosarcoma tumorigenesis and development are extremely important to intensify the treatment efficacy of osteosarcoma and further improve patients’ prognosis
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