Long non‑coding RNA FER1L4 inhibits cell proliferation and metastasis through regulation of the PI3K/AKT signaling pathway in lung cancer cells

Abstract

Lung cancer is among the most common malignancies worldwide; however, the current understanding of its detailed mechanism remains limited. Long non-coding RNAs (lncRNAs) were previously identified to serve significant roles in tumorigenesis. The present study aimed to investigate the role of a novel lncRNA, Fer-1-like family member 4 (FER1L4), in lung tumorigenesis. In the present study, it was demonstrated that the expression level of FER1L4 was significantly decreased in clinical lung cancer tissues and in cultured lung cancer cells, as evidenced by reverse transcription-quantitative polymerase chain reaction analysis. Overexpression of FER1L4 in lung cancer cell lines A549 and 95D inhibited colony formation, cell proliferation and cell migration capacity, measured by colony formation assays, cell proliferation assays and Transwell assays, respectively. Overexpression of FER1L4 led to a reduction in the expression levels of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) in A549 and 95D cells, whereas, activation of PI3K/Akt signaling using a small molecular inhibitor of phosphatase and tensin homolog, reversed the inhibitory effects of FER1L4 on cell proliferation and metastasis. All of these results suggested that the lncRNA FER1L4 suppressed cell proliferation and metastasis by inhibiting the PI3K/Akt signaling pathway in lung cancer.

Functions of Vertebrate Ferlins

“…In humans, the long non-coding RNA Fer1L4 plays a role in signaling, controlling cell proliferation, migration and apoptosis. 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].…”

“…In zebrafish tissues otoferlins a and b transcripts were detected in the sensory hair cells of the inner ear, otoferlin a in the mid-brain and retinal ganglion cell layer, whereas otoferlin b was in the hair cells of the lateral line [26]. Initially, Fer1L4 long noncoding RNA was found to be selectively transcribed in human stomach tissue [33], however, later Fer1L4 was detected in multiple normal tissues surrounding malignant tumors [65][66][67][68]. Fer1L5 is produced in myotubes [69], pancreas and at lower levels in a few other human tissues [33].…”

“…PTEN is known as a tumor suppressor inhibiting PI3K/AKT proliferation signaling. Downregulation of Fer1L4 expression correlated with decrease of the level of PTEN [164,166], while Fer1L4 overexpression inhibited the PI3K/AKT signaling pathway [67,163]. Thus, the Fer1L4 RNA may serve as a competing endogenous RNA and regulate the expression of PTEN via miRNA-mediated mechanisms inhibiting cancer cell proliferation and metastasis [164,166].…”

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

“…7a, b). The activity of PI3K/AKT pathway was critical for survival and proliferation of prostate cancer and tightly regulated by FER1L4 in several cancer types [30,31]. Interestingly, in PC-3 and DU145 cells, we also observed that FER1L4 overexpression decreased the phosphorylation of AKT protein which was reversed towards FBXW7 silencing ( Fig.…”

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

“…FER1L4, a novel LncRNA, was first identified that its down‐regulated expression in human gastric cancer . Gao et al also found that FER1L4 was down‐regulated in NSCLC in vivo and in vitro, and overexpression of FER1L4 could inhibit cell metastasis through regulating the PI3K/Akt signal pathway . Many studies indicated that the PI3K/Akt signalling was aberrantly activated in human malignancies and was associated with tumour metastasis and drug resistance …”