FER1L4/miR‐372/E2F1 works as a ceRNA system to regulate the proliferation and cell cycle of glioma cells

Abstract

Long non‐coding RNAs have recently become a key regulatory factor for cancers, whereas FER1L4, a newly discovered long non‐coding RNA, has been mostly studied in gastric carcinoma and colon cancer cases. The functions and molecular mechanism of FER1L4 have been rarely reported in glioma malignant phenotypes. In this study, it was found that the expression of LncRNA FER1L4 is upregulated in high‐grade gliomas than in low‐grade cases and that a high expression of LncRNA FER1L4 predicts poor prognosis of gliomas. Meanwhile, in vitro study suggests that expression of FER1L4 with SiRNA knockdown obviously suppresses cell cycle and proliferation. It is further demonstrated by experiments that the FER1L4 knockdown suppresses growth of in vivo glioma. Besides, it is found in our study that LncRNA FER1L4 expression is positively correlated with E2F1 mRNA expression. After knockdown of FER1L4 expression, E2F1 expression is significantly down‐regulated, whereas the expression of miR‐372 is significantly up‐regulated; the up‐regulation of miR‐372 leads to significant down‐regulation of FER1L4 and E2F1 expression. In addition, it is also found that FER1L4 can be used as competitive endogenous RNA to interact or bind with miR‐371 and thereby up‐regulate E2F1, thus promoting the cycle and proliferation of glioma cells. It may be one of the molecular mechanisms in which FER1L4 plays its oncogene‐like role in gliomas.

Functions of Vertebrate Ferlins

“…The results of the vast majority of the studies are consistent with a function of Fer1L4 as a tumor suppressor in multiple types of cancer [32,[66][67][68]160,161]. The exception is a report about the Fer1L4 possible role in glioma progression, where high expression of Fer1L4 was associated with a poor disease prognosis [162]. Fer1L4 exerts its function via the PTEN/PI3K/AKT signaling pathway [161,163,164].…”

Long non-coding RNA FER1L4 inhibits prostate cancer progression via sponging miR-92a-3p and upregulation of FBXW7

“…**p < 0.01; ***p < 0.001 significantly downregulated lncRNAs in gastric cancer via bioinformatic analysis of lncRNA microarray data [34]. Later, several studies suggested that FER1L4 could function as an oncogene or a tumor suppressor in different cancer types [18,[35][36][37]. The most well-characterized role of FER1L4 is its tumor suppressor function as a negative regulator of AKT signaling in cancers [30,31].…”

“…Studies showed that FER1L4 functioned as a ceRNA to regulate gene expression and disease progression [18,28]. Using RegRNA 2.0, miR-92a-3p was predicted as a potential binding miRNA for FER1L4 with the highest score.…”

“…LncRNA MEG3 sponged miR-9-5p, upregulated QKI-5 and suppressed prostate cancer cell proliferation, migration, invasion and induced apoptosis [16]. Fer-1-like protein 4 (FER1L4) have recently attracted the researchers' attention due to its involvement in the progression of cancer [17,18]. The biological role and molecular mechanism of FER1L4 in prostate cancer is unknown.…”

Integrated analyses of early responses to radiation in glioblastoma identify new alterations in RNA processing and candidate target genes to improve treatment outcomes

“…Besides its known effect on cell cycle regulation and DNA replication, it is also a positive regulator of telomerase activity, binding the TERT promoter[68]. Recent studies show that lncRNAs and miRNAs function in an antagonistic fashion to regulate E2F1 expression, ultimately affecting cell proliferation, glioblastoma growth, and response to therapy[69,70,71]. E2F2 has been linked to the maintenance of glioma stem cell phenotypes and cell transformation[72,73].…”