Open AccessDecreased long non‐coding RNA lincFOXF1 indicates poor progression and promotes cell migration and metastasis in osteosarcoma
Author(s) -
Yang Shengquan,
Chen Jian,
Lv Bin,
Zhang Jun,
Li Deli,
Huang Mengyuan,
Yuan Li,
Yin Guoyong
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15828
Subject(s) - osteosarcoma , cancer research , biology , cell migration , metastasis , long non coding rna , ezh2 , microrna , cell , rna , cancer , gene expression , gene , genetics
Long non‐coding RNAs have been demonstrated to be important regulators of various cancers, though the precise mechanisms remain unclear. Although lincFOXF1 has been reported to act as a tumour suppressor, its function and underlying mechanisms in osteosarcoma have not yet been explored. We employed quantitative real‐time polymerase chain reaction (qRT‐PCR) to evaluate the expression of lincFOXF1 and GAPDH in osteosarcoma tissues and cell lines, and colony‐formation, CCK8, wound‐healing, and transwell assays were conducted to analyse the proliferation, migration, and invasion capacity of osteosarcoma cells. Subcellular localization analysis by fractionation and RNA immunoprecipitation assays were performed to elucidate the mechanism responsible for lincFOXF1‐mediated phenotypes of osteosarcoma cells. The results revealed that lincFOXF1 expression is significantly decreased and strongly related to Enneking stage as well as metastasis in osteosarcoma patients. Further experiments showed that lincFOXF1 inhibits the migration, invasion and metastasis of cells in vitro and vivo. Mechanistic investigation demonstrated that lincFOXF1 physically binds to EZH2, a polycomb repressive complex 2 (PRC2) component, and a search for downstream targets suggested that G‐protein‐coupled receptor kinase‐interacting protein 1 (GIT1) is involved in the lincFOXF1‐mediated repression of osteosarcoma cells migration and invasion. Moreover, GIT1 expression is inversely correlated with lincFOXF1 in osteosarcoma. The present findings indicate that lincFOXF1 is involved in the progression of osteosarcoma through binding with EZH2, further regulating GIT1 expression. Our results suggest that lincFOXF1 may serve as a biomarker and therapeutic target for osteosarcoma patients.