LncRNA is a type of RNA that is more than 200 nucleotides in length and does not code proteins.22,23 Nowadays, many studies have confirmed that lncRNAs play crucial roles in the occurrence and development of NSCLC, which may be considered as diagnostic and prognostic markers.24,25 Fer-1-like protein 4 (FER1L4), a novel long non-coding RNA, is reported to be implicated with the initiation and progression of multiple cancers by regulating cell proliferation, apoptosis, migration and invasion.14–16 Moreover, FER1L4 is correlated with prognosis.13,14,17,19,20 For example, Fei, et al. reported that FER1L4 upregulation significantly suppressed cell proliferation, colony formation, migration and invasion in osteosarcoma and associated with TNM stage, lymph node metastases and poor overall survival.14 Ma et al. showed that FER1L4 overexpression could inhibit cell proliferation and invasion, and promote apoptosis in esophageal squamous cell carcinoma.15 Qiao et al. revealed that FER1L4 suppressed cell proliferation and cycle in endometrial carcinoma.16 Chen et al. showed that FER1L4 was significantly associated with disease stage, metastasis and tumor differentiation, and might be a prognostic marker in osteosarcoma.13 Wu et al. reported that FER1L4 acted as a tumor suppressor and predicted good prognosis in hepatocellular carcinoma.19 Yue et al. reported that FER1L4 suppressed oncogenesis and exhibited prognostic value in colon cancer.20
In this study, our data showed that the expression levels of FER1L4 in NSCLC tissues was significantly decreased compared with those in matched adjacent normal lung tissues. It was consistent with the observations in other cancers.13–20 These data indicated lncRNA FER1L4 depletion was implicated with the formation of NSCLC, which might be helpful for the diagnosis of NSCLC. Moreover, lncRNA FER1L4 downregulation was closely associated with tumor size, TNM stage and lymph node metastasis, indicating that lncRNA FER1L4 depletion might correlate with tumor progression. NSCLC patients with FER1L4 over-expression had more favorable survival compared with those with low-expression, suggesting that lncRNA FER1L4 was a prognostic biomarker in NSCLC. In addition, our results showed that lncRNA FER1L4 knockdown significantly promoted cell proliferation, which further supported that lncRNA FER1L4 down-regulation might be connected with tumor progression. Therefore, these data further supported that lncRNA FER1L4 was as a tumor suppressor and correlated with the formation and progression of NSCLC.
However, there are also some limitations in present study. Firstly, the effect of lncRNA FER1L4 on cell proliferation was only confirmed in vitro, which needed to be further validated in vivo. Secondly, the exact mechanism of lncRNA FER1L4 in NSCLC remains unknown. Therefore, further investigations are needed to validate our findings.
In conclusion, these data indicated that lncRNA FER1L4 was lowly expressed in NSCLC tissues and affected cell proliferation in NSCLC. Moreover, overexpression of lncRNA FER1L4 predicted favorable prognosis in NSCLC patients, which might serve as a potential biomarker.