Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Dan Fei; Xiaona Zhang; Jinxiang Liu; Long Tan; Jie Xing; Dongxu Zhao; Yang Zhang

doi:10.1159/000495554

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Cell Physiol Biochem. 2018;51(3):1364-1375. doi: 10.1159/000495554. Epub 2018 Nov 27.

Authors

Dan Fei¹, Xiaona Zhang², Jinxiang Liu³, Long Tan¹, Jie Xing¹, Dongxu Zhao⁴, Yang Zhang⁵

Affiliations

¹ Department of Ultrasonographic, China-Japan Union Hospital of Jilin University, Changchun, China.
² Department of Anesthesiology, the First Hospital of Jilin University, Changchun, China.
³ Department of Pediatrics, the First Hospital of Jilin University, Changchun, China.
⁴ Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Chinazhaodongxu909@sina.com.
⁵ Department of Neurosurgery, the First Hospital of Jilin University, Changchun, China.

PMID: 30481787
DOI: 10.1159/000495554

Abstract

Background/aims: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism.

Methods: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created.

Results: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues.

Conclusion: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.

Keywords: FERIL4; Long non-coding RNA; Osteosarcoma; PTEN; miR-18a-5p.

Publication types

Retracted Publication

MeSH terms

Adult
Bone Neoplasms / diagnosis
Bone Neoplasms / genetics*
Bone Neoplasms / pathology
Carcinogenesis / genetics*
Carcinogenesis / pathology
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic*
Humans
Male
MicroRNAs / genetics*
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
Osteosarcoma / diagnosis
Osteosarcoma / genetics*
Osteosarcoma / pathology
PTEN Phosphohydrolase / genetics*
Prognosis
RNA, Long Noncoding / genetics*
Young Adult

Substances

MIRN18A microRNA, human
MicroRNAs
RNA, Long Noncoding
long non-coding RNA FER1L4, human
PTEN Phosphohydrolase
PTEN protein, human