SP1-mediated upregulation of lncRNA ILF3-AS1 functions a ceRNA for miR-212 to contribute to osteosarcoma progression via modulation of SOX5
Introduction
Osteosarcoma is the most common histological form of primary bone cancer that predominantly affects children, adolescents and young adults, accounting for 20–35% of all malignant primary bone tumors [1]. Despite the development treatment approaches of osteosarcoma such as chemotherapy and curative resection, the overall 5-year survival rate of osteosarcoma patients remains poor due to metastases and relapse [2]. The potential mechanisms involved in the development and progression of osteosarcoma remain poorly understood. Therefore, it is important for us to elucidate the molecular mechanisms underlying osteosarcoma progression for the development of novel diagnostic biomarkers and therapeutic strategies.
Long noncoding RNA (lncRNA) is another class of noncoding RNA with more than 200 nucleotides in length and were initially thought to be ‘transcriptional noise’ [3]. Recently, increasing evidence shows that lncRNAs are involved in a large number of biological processes, such as differentiation, evolutionary conservation, chromosome imprinting, chromatin modification, cell cycle regulation and cytoplasmic transport [4]. LncRNAs are abnormally expressed in various diseases and can drive important cancer phenotypes by serving as anti-oncogenes and tumor promoters [5]. Up to date, several lncRNAs had been identified to be associated with the progression of osteosarcoma. For instance, lncRNA LINC00858 was found to promote osteosarcoma cells proliferation and metastasis via the regulation of miR-139-CDK14 axis [6]. LncRNA TP73-AS1 was reported to be highly expressed in osteosarcoma and its knockdown suppressed osteosarcoma cell proliferation and invasion by targeting miR-142 [7]. Nevertheless, the detail molecular mechanism of lncRNA during osteosarcoma carcinogenesis is still sustain unclear.
LnRNA ILF3-AS1 (ILF3-AS1), located at 17p13.1, was a newly identified lncRNA which had been reported to be dysregulated in several tumors, such as melanoma and colon cancer, and cervical squamous cell carcinoma [[8], [9], [10]]. In addition, its tumor-promotive roles were also confirmed in melanoma. However, whether ILF3-AS1 was abnormally expressed in osteosarcoma, and its potential clinical significance and biological function have not been investigated. In this study, we firstly provided evidences that ILF3-AS1 upregulated by transcription factor SP1 served as a tumor promoter in osteosarcoma via regulation of miR-212-SOX5 pathway, suggesting that ILF3-AS1 may be a potential biomarker and a therapeutic target of osteosarcoma.
Section snippets
Human tissue samples
The osteosarcoma tissue specimens and matched adjacent normal tissues were collected from 121 osteosarcoma patients (range from January 2008 to November 2011) at The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University. This study was approved by the Ethics Committee of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University and written informed consents were obtained from all patients. Relevant clinical information of the patients was shown in Table S2.
Cell culture and cell transfection
We
ILF3-AS1 was highly expressed in osteosarcoma and associated with poor prognosis
Firstly, we performed RT-PCR to investigate whether ILF3-AS1 was abnormally expressed in osteosarcoma and the results showed that the expression levels of ILF3-AS1 was significantly up-regulated in osteosarcoma tissues compared to matched normal bone tissues (P < 0.01, Fig. 1A). In addition, we also observed that higher expression of ILF3-AS1 was associated with patients with advanced stages (Fig. 1B). Moreover, the expression levels of ILF3-AS1 was also significantly up-regulated in four
Discussion
The role of biomarkers in the management of cancer is quickly expanding and the identification of sensitive biomarkers is very important for the improvement of prognosis of osteosarcoma patients. Recently, the possible potential of lncRNAs as novel candidates attracted increasing attention [12]. In this study, we focused on a newly identified lncRNA ILF3-AS1. We found that ILF3-AS1 expression was significantly up-regulated in both osteosarcoma tissues and cell lines. Recently, growing evidences
Conflicts of interest
The authors declare no competing financial interests.
References (21)
- et al.
The Landscape of long noncoding RNA classification
Trends Genet.
(2015) - et al.
Long noncoding RNA LINC00858 promotes osteosarcoma through regulating miR-139-CDK14 axis
Biochem. Biophys. Res. Commun.
(2018) - et al.
Knockdown of long non-coding RNA TP73-AS1 inhibits osteosarcoma cell proliferation and invasion through sponging miR-142
Biomed. Pharmacother.
(2018) - et al.
Recurrence-associated long non-coding RNA signature for determining the risk of recurrence in patients with colon cancer
Mol. Ther. Nucleic Acids
(2018) - et al.
A 15-long non-coding RNA signature to improve prognosis prediction of cervical squamous cell carcinoma
Gynecol. Oncol.
(2018) - et al.
STAT1-mediated upregulation of lncRNA LINC00174 functions a ceRNA for miR-1910-3p to facilitate colorectal carcinoma progression through regulation of TAZ
Gene
(2018) - et al.
SP1-mediated downregulation of ADAMTS3 gene expression in osteosarcoma models
Gene
(2018) - et al.
Long non-coding RNA LINC00339 facilitates the tumorigenesis of non-small cell lung cancer by sponging miR-145 through targeting FOXM1
Biomed. Pharmacother.
(2018) - et al.
LncRNA CALML3-AS1 promotes tumorigenesis of bladder cancer via regulating ZBTB2 by suppression of microRNA-4316
Biochem. Biophys. Res. Commun.
(2018) - et al.
Global cancer statistics, 2012
CA A Cancer J. Clin.
(2015)